Female Infertility & IV

A Pilot Study Evaluating the Combination of Acupuncture with Sildenafil on Endometrial Thickness

Lorne Brown — Tue, 13 Dec 2011 17:09:12 -0800

A Pilot Study Evaluating the Combination of Acupuncture with Sildenafil on Endometrial Thickness

Conclusions: This pilot study is consistent with previous reports that acupuncture improves uterine lining measurements over previous cycles.

Wendy Yu, L.Ac., Brandon Horn, J.D., L.Ac., Brian Acacio, M.D., Daoshing Ni, D.O.M, L.Ac., Ph.D., Rudy Quintero, M.D., Mory Nouriani, M.D.

Sher Institutes for Reproductive Medicine, Glendale, CA and Eastern Center for Complementary Medicine, Los Angeles, CA

Introduction

Endometrial thickness has been shown to be an important prognostic factor of successful embryo implantation. If the endometrial thickness is less than 9 mm there is a significant reduction in live birth rates. Though there is
conflicting data, preliminary evidence suggests that the administration of vaginal Sildenafil can markedly improve endometrial thickness and result in increased live IVF births. Our clinical observations are consistent with
this. However, other clinics report inconsistent results. Therefore, we hypothesized that the difference in response between clinics may involve other factors. When we looked into this, we found that many of our patients were simultaneously receiving acupuncture treatments.

Studies on acupuncture have demonstrated positive effects on implantation rates, ongoing pregnancy rates and the number of live births. Acupuncture has also been shown, via measurements of pulsatility index, to significantly increase blood flow to the uterus. Decreases in pulsatility index have been shown to significantly improve pregnancy rates. Researchers have also found that acupuncture has direct effects on the endometrium. Some of these include increases in progesterone receptor concentration, a reduction in COX-2, and an increase in the activity of nitric oxide synthase. Therefore, the purpose of our investigation was to evaluate the effects of combining acupuncture and Sildenafil suppositories on endometrial lining.

Materials and methods

Subjects were initially five females, ages 35 - 45, with prior IVF or IUI failures. However, one subject was later disqualified due to the discovery of an undisclosed prior lining of 9 mm. All subjects had a Day 3 FSH < 9 mlU/ml and normal uterine cavity by fluid ultrasound or hysteroscopy. Patients were excluded if they had known allergies to any fertility medications, a history of estrogen dependent neoplasms, abnormal uterine cavity, history of DES exposure or Asherman’s syndrome.

Following IRB approval, consent, routine tests, FSH and estradiol levels were obtained for each patient and either a fluid ultrasound or HSG was performed less than 6 months prior to initiation of treatment. Protocols were designed for each patient using the fertility clinic’s standard techniques for evaluating the necessary dosage of gonadotropins. Patients received a Lupron long protocol using 300 to 450 units of gonadotropin depending on age, prior IVF history and day 3 FSH value.

Each patient was given 25 mg Sildenafil suppositories on CD9 and a series of five acupuncture treatments provided by two acupuncturists who are certified by the National Certification Commission for Acupuncture and Oriental Medicine and the State of California. Thirty four gauge 1.5 inch and 38 gauge 1 inch needles (Millenia, China) were used depending on the location of the acupoints. The 34 gauge needles were used on points located on the trunk of the body and the 38 gauge needles used on the extremities. A far infrared lamp (TDP, China) was utilized for 20 minutes on the lower abdomen, approximately 12-18 inches from the skin’s surface. The base protocol included the following
acupoints:

Conception Vessel 4	Spleen 6
Conception Vessel 6	Spleen 10
Large Intestine 10	Stomach 36
Kidney 3

Microcurrent stimulation (Electrostimulator 8c.Pro, Pantheon Research, CA) was applied using standard leads in biphasic mode using 10 Hz from (L) Kidney 3 to Conception Vessel 4 and from (R) Kidney 3 to Conception Vessel 6. Needle-moxa was then applied to Conception Vessel 4 and Conception Vessel 6 in the form of Japanese kyutoshin. In accordance with Japanese meridian therapy, acupoint modifications were then made if any of the following areas were uncomfortable to the patient upon 2 kg palpation.

Location of palpation response	Protocol Addition
(L) Stomach 27-28	(L) Liver 4
(R) Stomach 27-28	(R) Spleen 9
Kidney 16	Ipsilateral Kidney 6
Kidney 2	Ipsilateral Kidney 10

Treatments were administered according to the following schedule:

Week	# of Tx	Treatment Timing
1	2	> 2 day space between tx
2	3	<1 day space between tx

Uterine lining was measured during patients’ routine monitoring via fluid ultrasounds which were provided starting from cycle day 3 and repeated throughout stimulation phase.

Results

All four subjects achieved endometrial lining thickness of greater than or equal to 10 mm following the administration of the combination of acupuncture and Sildenafil: including one patient whose lining did not exceed 5 mm in a previous cycle. Another patient, who had not responded to Sildenafil alone in a prior IVF cycle, responded to the combination of Sildenafil and acupuncture. We also noted that endometrial thickness in most patients continued to increase post- CG administration.

Conclusions

This pilot study is consistent with previous reports that acupuncture improves uterine lining measurements over previous cycles.

This preliminary data supports the potential for a synergistic action between acupuncture and Sildenafil. We hypothesize these effects may be due to acupuncture’s ability to upregulate nitric oxide synthase. However,
we cannot rule out other mechanisms of action since acupuncture has also been shown to affect many other parameters.

The results of this preliminary data may also suggest a role for a similar combination in treating erectile dysfunction. Further testing and data is necessary to verify these results.

Literature cited

Hou, L.Q., Xiong, K.R. 2006. Effect of different needle-retained time of electroacupuncture on expression of nitric oxide synthase in the septum of the rat. Zhongguo Zhen Jiu 26:879-882.
Kim, J., Shin, K.H., and Na, C.S. 2000. Effect of acupuncture treatment on uterine motility and cyclooxygenase-2 expression in pregnant rats. Gynecological and Obstetrics Investigation 50:225-230.
Matsumoto, K. and Euler, D. 2002. Kiiko Matsumoto’s Clinical Strategies: In the Spirit of Master Nagano, Vol. 1. Kiiko Matsumoto International, Massachusetts.
Paulus, W.E., Zhang, M., Strehler, E., El-Danasouri, I., and Sterzik, K. 2002. Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy. Fertility and Sterility 77:721-724.
Quintero, R. et al. 2004. A randomized, double-blind, controlled crossover study evaluating acupuncture as an adjunct to in-vitro fertilization. Fertility and Sterility 81:S3.
Sher, G., and Fisch, J.D. 2002. Effect of vaginal sildenafil on the outcome of in vitro fertilization (IVF) after multiple IVF failures attributed to poor endometrial development. Fertility and Sterility 78:1256-1257.
Stener-Victorin, E., Waldenstrom, U., Andersson, S.A., and Wikland, M. 1996. Reduction of blood flow impedance in the uterine arteries of infertile women with electro-acupuncture. Human Reproduction 11:1314-1317.
Tian, D., Xie, X., and Wang, B. 1998. Study on the relationship between ovulation inducing effect of drug-acupuncture and endometrial contents of estradiol receptor and progesterone receptor. Zhongguo Zhong Xi Yi Jie He Za Zhi 18:225-226.

Acknowledgments

We’d like to thank the late Dr. Mory Nouriani for coordinating and bringing this study to fruition. The loss of Dr. Nouriani has created a significant void in the field of reproductive medicine and he will be greatly missed by his patients, the practitioners and staff of both the Sher Institutes for Reproductive Medicine and the Eastern Center for Complementary
Medicine. Our thoughts are with his wife, Dr. Kerri Parks and his 4 young children, Olivia, Nicholas, William and Mora. We would also like to thank Ferring Pharmaceuticals Inc. for providing the funds to make this study possible.

For further information

Please contact wendy [at] herbalroom [dot] com. More information on this and other acupuncture studies that relate to reproductive medicine can be found at www.herbalroom.com.

Efficacy of Traditional Chinese Herbal Medicine in the management of female infertility: A systematic review.

Lorne Brown — Tue, 29 Nov 2011 07:17:17 -0800

Efficacy of Traditional Chinese Herbal Medicine in the management of female infertility: A systematic review.
Ried K, Stuart K.

Source
Discipline of General Practice, School of Population Health & Clinical Practice, The University of Adelaide, South Australia 5005, Australia.
Abstract

OBJECTIVES:
To assess the effect of Traditional Chinese Herbal Medicine (CHM) in the management of female infertility and on pregnancy rates compared with Western Medical (WM) treatment.

METHODS:
We searched the Medline and Cochrane databases and Google Scholar until February 2010 for abstracts in English of studies investigating infertility, menstrual health and Traditional Chinese Medicine (TCM). We undertook meta-analyses of (non-)randomised controlled trials (RCTs) or cohort studies, and compared clinical pregnancy rates achieved with CHM versus WM drug treatment or in vitro fertilisation (IVF). In addition, we collated common TCM pattern diagnosis in infertility in relation to the quality of the menstrual cycle and associated symptoms.

RESULTS:
Eight RCTs, 13 cohort studies, 3 case series and 6 case studies involving 1851 women with infertility were included in the systematic review. Meta-analysis of RCTs suggested a 3.5 greater likelihood of achieving a pregnancy with CHM therapy over a 4-month period compared with WM drug therapy alone (odds ratio=3.5, 95% CI: 2.3, 5.2, p<0.0001, n=1005). Mean (SD) pregnancy rates were 60±12.5% for CHM compared with 32±10% using WM drug therapy. Meta-analysis of selected cohort studies (n=616 women) suggested a mean clinical pregnancy rate of 50% using CHM compared with IVF (30%) (p<0.0001).

CONCLUSIONS:
Our review suggests that management of female infertility with Chinese Herbal Medicine can improve pregnancy rates 2-fold within a 4 month period compared with Western Medical fertility drug therapy or IVF. Assessment of the quality of the menstrual cycle, integral to TCM diagnosis, appears to be fundamental to successful treatment of female infertility.

Complement Ther Med. 2011 Dec;19(6):319-31. Epub 2011 Oct 5.

Research shows Chinese herbal formula is appropriate for use in treating PCOS in women

Lorne Brown — Mon, 05 Sep 2011 22:28:31 -0700

This finding indicates that wen-jing-tang Chinese herbal formula is appropriate for use in treating PCOS in women with various constitutions.

Click here to read study abstract.

Hypnopuncture - Combining Acupuncture with Hypnosis for Fertility

Lorne Brown — Mon, 08 Aug 2011 13:01:03 -0700

Hypnopuncture - Combining Acupuncture with Hypnosis for Fertility now available at Acubalance

Acubalance Wellness Centre is the first clinic in BC to offer hypno-acupuncture for fertility. New studies show that thoughts, fears, emotions and old issues create stress reactions that can interfere with conception and pregnancy. Hypno-acupuncture is ground- breaking therapy that combines the healing power of hypnotherapy and acupuncture to relieve stress, eliminate unconscious blocks and restore the body’s natural fertility.

Potential Synergism between Hypnosis and Acupuncture—Is the Whole More Than the Sum of Its Parts?

Evid Based Complement Alternat Med. 2007 June; 4(2): 233–240.
Published online 2006 October 31. doi: 10.1093/ecam/nel069

Click here for research abstract

Both hypnosis and acupuncture have gained credibility over the years in their effectiveness for treating various health conditions. Currently, each of these treatments is administered in distinct settings and separate times. That is, even if patients receive both treatments as part of a multidimensional therapeutic program, they would typically receive them separately rather than simultaneously at the same session. This separation however might be undesirable since, at least theoretically, hypnosis and acupuncture could potentially augment each other if administered concomitantly. In this article we outline the rationale for this hypothesis and discuss the potential ramifications of its implementation.

Click here for research abstract

The use of Co Q10 to improve the outcome of Vancouver infertility treatment in older patients

Lorne Brown — Wed, 27 Jul 2011 19:47:22 -0700

The use of Co Q10 to improve the outcome of Vancouver infertility treatment in older patients  

We wanted to share this paper published in the prestigious journal of Fertility Sterility 2010;93:272–5. Ó2010. They hypothesize that dietary supplementation of mitochondrial nutrients, in particular Coenzyme Q10 (Co Q10) may improve the availability of mitochondrial energy production for the maturing oocyte and developing embryo, thereby reducing the rate of chromosomal nondisjunction and improving implantation in older infertile patients

We have been recommending Co Q10 since 2007 for our Vancouver fertility patients along with acupuncture and herbs. There are many natural options available to couples with either male and/or female fertility. Ask your Acubalance practitioner what is the ideal dosage of Co Q10 for you.

"…….One study has looked into the effect of CoQ10 as a supplement for the in vitro culture of bovine embryos and found a significantly higher rate of early embryo cleavage, blastocyst formation rate, hatching rate, percentage of expanding blastocysts, and a larger size of the inner cell mass (ICM). In addition, there was an in- creased ATP content in the group of embryos cultured with CoQ10. All of those parameters suggest better quality embryos."

"……In conclusion, we have presented evidence for mitochondrial involvement in age-related changes in the oocyte. In light of the prior literature and our preliminary animal data, we believe that supplementing the diets of older women with mitochondrial nutrients may result in an improvement of oocyte and embryo quality, and subsequently, better pregnancy outcome. By in- creasing energy for chromosomal disjunction, this intervention may be able to reduce the risk of trisomy and other types of chromosomal aneuploidies related to oocyte aging. In addition, increased mitochondrial energy production may improve embryo cleavage and reduce cytoplasmic fragmentation. Mitochondrial nutrients are naturally occurring vitamins that have been used successfully to treat conditions associated with diminished energy production from mitochondria, and appear to be very safe in the doses studied. We believe that a clinical trial looking at the role of CoQ10 supplementation as a way to improve oocyte and embryo quality is worthwhile and hence we have initiated a randomized placebo-controlled study to test the validity of this hypothesis in older women undergoing fertility treatments."

To book an appointment or request a free 15 min consult please click here

Low-frequency Electro-Acupuncture and Physical Exercise Decrease High Muscle Sympathetic Nerve Activity in Polycystic Ovary Synd

Melissa — Tue, 21 Jul 2009 19:58:06 -0700

Conclusions: For the first time we demonstrate that low-frequency EA and physical exercise lowers high sympathetic nerve activity in women with PCOS. Thus, treatment with low-frequency EA or physical exercise with the aim to reduce MSNA may be of importance for
women with PCOS.

Elisabet Stener-Victorin1*, Elizabeth Jedel2, Per Olof Janson, and Yrsa Bergmann Sverrisdottir3

1 Institution of Neuroscience and Physiology
2 Osher Center for Integrative Medicine
3 inst. neuroscience and physiology

* To whom correspondence should be addressed. E-mail: elisabet [dot] stener-victorin [at] neuro [dot] gu [dot] se.

Context: We have recently shown that polycystic ovary syndrome (PCOS) is associated with high muscle sympathetic nerve activity. Animal studies support the concept that low-frequency electro-acupuncture (EA) and physical exercise, via stimulation of ergoreceptors and somatic afferents in the muscles, may modulate the activity of the sympathetic nervous system. Objective: The aim of the present study was to investigate the effect of these interventions on sympathetic nerve activity in women with PCOS.

Design: Randomized controlled trial.

Setting: Sahlgrenska University Hospital, Gothenburg, Sweden.

Outcome Measures and Subjects: Twenty women with PCOS were randomly allocated to one of three groups; low-frequency EA (n=9), physical exercise (n=5) or to an untreated control (n=6) group during 16 weeks. Direct recordings of multiunit efferent postganglionic muscle sympathetic nerve activity (MSNA) in a muscle fascicle of the peroneal nerve before and following 16 weeks of treatment. Biometric, hemodynamic, endocrine and metabolic parameters were measured.

Results: Low-frequency EA (P = 0.036) and physical exercise (P = 0.030) decreased MSNA burst frequency compared to the untreated control group. Low-frequency EA group reduced sagittal diameter (P = 0.001), while physical exercise group reduced body weight (P = 0.004) and body mass index (BMI) (P = 0.004) as compared to the untreated control group. Sagittal diameter was related to MSNA burst frequency (Rs = 0.58, P < 0.005) in the EA group. No correlation was found for BMI and MSNA in the exercise group. There were no differences between the groups in hemodynamic, endocrine and metabolic variables.

Prolonged treatment with N-acetylcysteine andL-arginine restores gonadal function in patients with PCO syndrome

Lorne Brown — Sun, 12 Jul 2009 07:42:37 -0700

Conclusions: This preliminary, open study shows that prolonged, oral treatment with combined administration of NAC and ARG determines a clear increase in the number of menstrual cycles, likely ovulatory, in patients with PCOS. These data therefore support the hypothesis that the treatment acts by increasing NO availability counteracting exaggerated free radicals that connote the PCOS. These finding have to be verified in a more prolonged, double blind, placebo controlled study in PCOS patients.

Introduction:
Nitric oxide (NO) plays a wide spectrum of biological actions including a positive role in oocyte maturation and ovulation. Free radicals have been shown elevated in PCOS and therefore would be responsible for quenching NO that, in turn, would play a role in determining oligo or
amenorrhea connoting PCOS. We recently demonstrated that the combined administration of N-acetylcysteine (NAC) and arginine (ARG) is able to exert an antioxidant action leading to an increase in NO availability in patients with type 2 diabetes mellitus, another
condition characterized by insulin-resistance and endothelial dysfunction.

Aim: Aim of the study was to evaluate the effects of a prolonged treatment with NAC and ARG in patients with PCOS, focusing on their ovarian function as well as on some metabolic parameters.

Materials
and methods: Eight patients with PCOS displaying oligo-amenorrhea from at least 1 year underwent a combined treatment with NAC (1200 mg/die) plus ARG (1600 mg/die) for 6 months. Menstrual function, glucose and insulin levels, and in turn HOMA index, were monitored.

Results:
Menstrual function was restored as indicated by the number of uterine bleedings under treatment (3.00, 0.18–5.83 vs 0.00, 0.00–0.83; P<0.02). Also, a well-defined biphasic pattern in the basal body temperature in 21 out of a total of 24 cycles under treatment suggested ovulatory cycles. The HOMA index decreased under treatment (2.12, 1.46 4.42 vs 3.48, 1.62 5.95; P<0.05).

Conclusions: This preliminary, open study shows that prolonged, oral treatment with combined administration of NAC and ARG determines a clear increase in the number of menstrual cycles, likely ovulatory, in patients with PCOS. These data therefore support the hypothesis that the treatment acts by increasing NO availability counteracting exaggerated free radicals that connote the PCOS. These finding have to be verified in a more prolonged, double blind, placebo controlled study in PCOS patients.

Endocrine Abstracts (2009) 20 P657

Andi Masha, Chiara Manieri, Stefano Dinatale, Guido Albino Bruno, Ezio Ghigo & Valentino Martina

Division of Endocrinology, Department of Internal Medicine, University of Turin, Turin, Italy.

Stress Responses in Women with PolyCystic Ovary Syndrome

AcuBweb — Wed, 25 Mar 2009 06:49:22 -0700

CONCLUSION: PCOS patients showed increased cortisol levels and heart rate reactivity as well as a reduced upregulation of IL-6 in response to stress. The altered stress reactivity in PCOS patients may constitute a link between depression, overweight, ovulatory disturbance, and the cardiovascular and diabetes risks associated with the diagnosis.

BACKGROUND: We analyzed the neuroendocrine and immune cell responses to psychosocial stress in PCOS patients compared to BMI-matched healthy controls. METHODS: Responses to public speaking stress were analyzed in 32 PCOS patients and 32 BMI-matched healthy controls. At baseline, during, and 10- and 45-min after stress, state anxiety, cardiovascular responses, cortisol, ACTH, as well as circulating leukocyte subpopulations were analyzed, together with hsCRP and serum IL-6 concentrations. RESULTS: In response to public speaking stress, both groups showed significant but comparable increases in state anxiety, and blood pressure (all p<0.001; time effects). The ACTH and cortisol stress responses were significantly enhanced in PCOS (both p<0.05; interaction effect). In addition, heart rate was significantly higher in PCOS (p<0.05; group effect). PCOS patients displayed a reduced upregulation of IL-6 levels in response to stress (p<0.05; interaction effect). Baseline levels of circulating leukocyte subpopulations, IL-6 and hsCRP concentrations did not differ between BMI-matched controls and PCOS patients. PCOS patients were characterized by markedly increased psychological distress. CONCLUSIONS: PCOS patients showed enhanced HPA-axis and heart rate reactivity as well as a reduced upregulation of IL-6 in response to stress. The altered stress reactivity in PCOS patients may constitute a link between depression, overweight, and the cardiovascular and diabetes risks associated with the diagnosis.

Psychoneuroendocrinology. 2009 Jan 14. Benson S, Arck PC, Tan S, Hahn S, Mann K, Rifaie N, Janssen OE, Schedlowski M, Elsenbruch S. Department of Medical Psychology and Behavioral Immunobiology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.

Acupuncture in Polycystic Ovary Syndrome: Current Experimental and Clinical Evidence

Melissa — Mon, 23 Feb 2009 11:15:23 -0800

Conclusion: Despite the lack of a large body of evidence, we should not ignore the fact that many women with PCOS use acupuncture. This alone is a compelling reason to investigate the method. In the hands of competent egistered health-practitioners, acupuncture is safe (96). Clinical and experimental evidence shows that cupuncture can be a suitable alternative or complement to pharmacological induction of ovulation in women with PCOS and may also relieve other symptoms, without adverse side-effects. Clearly, acupuncture odulates endogenous regulatory systems, including the sympathetic nervous system, the endocrine system and the neuroendocrine system. However, randomised controlled trials are needed to evaluate the effect of acupuncture in women with PCOS.

This review describes the aetiology and pathogenesis of polycystic ovary syndrome (PCOS) and evaluates the use of acupuncture to prevent and reduce symptoms related with PCOS. PCOS is the most common female endocrine disorder and it is strongly associated with hyperandrogenism, ovulatory dysfunction and obesity. PCOS increases the risk for metabolic disturbances such as hyperinsulinaemia and insulin resistance, which can lead to type 2 diabetes, hypertension and an increased likelihood of developing cardiovascular risk factors and impaired mental health later in life. Despite extensive research, little is known about the aetiology of PCOS. The syndrome is associated with peripheral and central factors that influence sympathetic nerve activity. Thus, the sympathetic nervous system may be an important factor in the development and maintenance of PCOS. Many women with PCOS require prolonged treatment. Current pharmacological approaches are effective but have adverse effects. Therefore, nonpharmacological treatment strategies need to be evaluated. Clearly, acupuncture can affect PCOS via modulation of endogenous regulatory systems, including the sympathetic nervous system, the endocrine and the neuroendocrine system. Experimental observations in rat models of steroid-induced polycystic ovaries and clinical data from studies in women with PCOS suggest that acupuncture exert long-lasting beneficial effects on metabolic and endocrine systems and ovulation.

Key words: acupuncture, insulin resistance, metabolic syndrome, obesity, opioids, ovulation, physical exercise, polycystic ovary syndrome, sympathetic nerve activity.

Effects on metabolic pattern
Low-frequency EA with repetitive muscle contractions activate physiological processes similar to those esulting from physical exercise. Daily low-frequency EA treatment induces weight loss and increases insulin ensitivity, reducing blood glucose and lipid levels (71, 72). Repeated low-frequency EA reduces food intake nd body weight, possibly by increasing leptin levels in both rats (71) and humans (72–75). Low-frequency EA also stimulates glucose transport in skeletal muscle independently of insulin and increase the insulin sensitivity of glucose transport in rats (76–78). In female rats with PCOS, induced by continuous prepubertal dministration of DHT (51), we found that both repeated low-frequency EA treatment and 4–5 weeks of voluntary exercise reduced insulin resistance (unpublished data). Exercise also reduced body fat and body eight an increased lean body mass. Thus, repeated low-frequency EA may reduce insulin resistance, a central feature of PCOS.

Journal of Neuroendocrinology

E. Stener-Victorin,* E. Jedel and L. Mannera°s*
*Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, Go¨teborg University, Go¨teborg, Sweden.

Osher Center for Integrative Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Assisted reproductive technology and major structural birth defects in the United States.

Melissa — Tue, 03 Feb 2009 17:35:22 -0800

CONCLUSIONS: These findings suggest that some birth defects occur more often among infants conceived with ART. Although the mechanism is not clear, couples considering ART should be informed of all potential risks and benefits.

Hum Reprod. 2009 Feb;24(2):360-6. Epub 2008 Nov 14.

Reefhuis J, Honein MA, Schieve LA, Correa A, Hobbs CA, Rasmussen SA; National Birth Defects Prevention Study.

National
Center on Birth Defects and Developmental Disabilities, Centers for
Disease Control and Prevention, 1600 Clifton Road N.E., MS E-86,
Atlanta, GA 30033, USA. nzr5 [at] cdc [dot] gov

BACKGROUND:
With >1% of US births occurring following use of assisted
reproductive technology (ART), it is critical to examine whether ART is
associated with birth defects.

METHODS: We analyzed data from the
National Birth Defects Prevention Study, a population-based,
multicenter, case-control study of birth defects. We included mothers
of fetuses or live-born infants with a major birth defect (case
infants) and mothers who had live-born infants who did not have a major
birth defect (control infants), delivered during the period October
1997-December 2003. We compared mothers who reported ART use (IVF or
ICSI) with those who had unassisted conceptions. Multiple logistic
regression was used to adjust for the following confounders: maternal
race/ethnicity, maternal age, smoking and parity; we stratified by
plurality.

RESULTS: ART was reported by 1.1% of all control mothers,
and by 4.5% of control mothers 35 years or older. Among singleton
births, ART was associated with septal heart defects (adjusted odds
ratio [aOR] = 2.1, 95% confidence intervals [CI] 1.1-4.0), cleft lip
with or without cleft palate (aOR = 2.4, 95% CI 1.2-5.1), esophageal
atresia (aOR = 4.5, 95% CI 1.9-10.5) and anorectal atresia (aOR = 3.7,
95% CI 1.5-9.1). Among multiple births, ART was not significantly
associated with any of the birth defects studied.

Contraceptive hormone use and cardiovascular disease.

Melissa — Tue, 03 Feb 2009 15:42:16 -0800

Conclusions: Existing data are mixed with regard to possible protection from OCs for atherosclerosis and cardiovascular events; longer-term cardiovascular follow-up of menopausal women with regard to prior OC use, including subgroup information regarding adequacy of ovulatory cycling, the presence of hyperandrogenic conditions, and the presence of prothrombotic genetic disorders is needed to address this important issue.

J Am Coll Cardiol. 2009 Jan 20;53(3):221-31.

Shufelt CL, Bairey Merz CN.

Women's Heart Center, Division of Cardiology, Department of Medicine, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Contraceptive hormones, most commonly prescribed as oral contraceptives (OCs), are a widely utilized method to prevent ovulation, implantation, and, therefore, pregnancy. The Women's Health Initiative demonstrated cardiovascular risk linked to menopausal hormone therapy among women without pre-existing cardiovascular disease, prompting a review of the safety, efficacy, and side effects of other forms of hormone therapy. A variety of basic science, animal, and human data suggests that contraceptive hormones have antiatheromatous effects; however, relatively less is known regarding the impact on atherosclerosis, thrombosis, vasomotion, and arrhythmogenesis. Newer generation OC formulations in use indicate no increased myocardial infarction risk for current users, but a persistent increased risk of venous thromboembolism. There are no cardiovascular data available for the newest generation contraceptive hormone formulations, including those that contain newer progestins that lower blood pressure, as well as the nonoral routes (transdermal and vaginal). Current guidelines indicate that, as with all medication, contraceptive hormones should be selected and initiated by weighing risks and benefits for the individual patient. Women 35 years and older should be assessed for cardiovascular risk factors including hypertension, smoking, diabetes, nephropathy, and other vascular diseases, including migraines, prior to use.

Implementation of dietary and general lifestyle advice among women with polycystic ovarian syndrome.

Melissa — Tue, 03 Feb 2009 15:25:08 -0800

CONCLUSION: In spite of the fact that weight loss and weight maintenance are absolutely vital in the treatment of PCOS, our study has shown that the support given to PCOS patients to help reduce and control their weight is inadequate and needs to be improved.
Humphreys L, Costarelli V.

Academy of Sport, Physical Activity and Wellbeing, London South Bank University, London SE1 0AA, UK.

AIMS: Central obesity and insulin resistance are strongly implicated in the etiology of polycystic ovarian syndrome (PCOS) and their reduction is therefore a central treatment focus. Weight loss has been consistently successful in reducing insulin resistance and restoring ovulation and fertility in women with PCOS. The purpose of the current study is to investigate the general attitudes towards dieting and exercise in women with PCOS, together with the extent of implementation of the dietary and lifestyle advice that these women are given as part of their treatment. General knowledge of patients about their condition (PCOS) has also been assessed. METHODS: Fifty three pre-menopausal women, over the age of 18 years, with a confirmed diagnosis of PCOS, were recruited from the Endocrinology Department, Middlesex Hospital, London. Subjects were interviewed individually using an interview-guided questionnaire. RESULTS: Sixty four per cent of the subjects were overweight (BMI > 25 kg/m2) and 55% of those were obese (BMI > 30 kg/m2). All subjects identified the importance of weight control in the management of their condition. However, only nine out of the 35 overweight women had actually been referred to a dietician and only 22 reported taking moderate exercise at least once a week in order to improve their health. The main sources of information on weight management were the internet and their consultant endocrinologist, who they normally see only twice a year. CONCLUSION: In spite of the fact that weight loss and weight maintenance are absolutely vital in the treatment of PCOS, our study has shown that the support given to PCOS patients to help reduce and control their weight is inadequate and needs to be improved.

Adult-specific over-expression of the Drosophila genes magu and hebe increases life span and modulates late-age female fecundity

AcuBweb — Mon, 02 Feb 2009 13:21:25 -0800

Conclusion: The data demonstrate that adult-specific over-expression of hebe and magu can increase life span and modulate female fecundity, and provide further evidence against obligatory trade-offs between reproduction and longevity.

Abstract During Drosophila aging mortality rate increases exponentially and progeny production per animal declines dramatically, correlating with decreased number and division of somatic and germ-line stem cells in the gonads. To search for genes that might promote both longevity and fecundity, a P element transposon (PdL), containing an outwardly directed, doxycycline-inducible promoter was used to generate conditional mutations. Mutant females were screened for increased fecundity at late ages in the presence of doxycycline. Two genes were identified, named hebe (CG1623) and magu (CG2264), that when over-expressed in adult flies could increase life span by ~5–30% in both sexes and increase female fecundity at late ages. Transcripts for magu are enriched in the Drosophila stem cell niche region, and magu encodes a protein related to the human SMOC2 regulator of angiogenesis. While moderate over-expression of magu in adult females increased fecundity at late ages, high-level over-expression of magu was maternal-effect lethal. The data demonstrate that adult-specific over-expression of hebe and magu can increase life span and modulate female fecundity, and provide further evidence against obligatory trade-offs between reproduction and longevity.

Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-2910, USA

Full text article: Click here

Study finds packaging chemical may hinder fertility

Melissa — Mon, 02 Feb 2009 09:49:15 -0800

Conclusion: A US study has found that perfluorinated chemicals (PFCs), which are used in areas such as food packaging, pesticides, clothing, carpets and personal care products, may be linked to infertility in women.

By Jane Byrne, 29-Jan-2009

The University of CaliforniaLos Angeles (UCLA) study of 1,240 women has found that those with
higher levels of PFCs in their bloodstreams tend to take longer to
become pregnant than those with lower levels.
The findings were published in the journal Human Reproduction today.
PFCs
are found in grease-resistant packaging such as microwave popcorn bags
and pizza boxes; they are also used in manufacturing processes, for
instance for industrial surfactants and emulsifiers.
Findings
According
to the authors, blood samples were taken at the time of the women's
first antenatal visit so that concentrations of the perfluorinated
chemicals PFOS andPFOA could be measured. >
The
researchers said they also interviewed the women at around the 12th
week of pregnancy to find out whether the pregnancy was planned or not
and how long it took them to become pregnant.
Infertility was defined as a time to pregnancy of longer than 12 months or infertility treatment
to establish the current pregnancy, and the results were adjusted for
potential confounding factors such as age, lifestyle and socio-economic
status, continued the report.
The levels of PFOS in the women's plasma ranged from 6.4 nanograms per
millilitre (ng/ml) to 106.7 ng/ml and from less than 1 ng/ml to 41.5
ng/ml for PFOA, the researchers found.
The
team divided the women's levels of PFOS/PFOA into four quartiles, and
found that, compared with women with the lowest levels of exposure, the
likelihood of infertility increased by 70-134 per cent for women in the
higher three quartiles of PFOS exposure and by 60-154 per cent for
those in the higher three quartiles of PFOA exposure.
Hormone interference
The
researchers said that the biological mechanisms by which exposure to
PFOS and PFOA might reduce fertility are unknown, but PFCs may
interfere with hormones that are involved in reproduction.
"Our
data showed that higher proportions of women reported irregular
menstrual periods in the upper three quartiles of PFOA and PFOS
compared with the lowest, and so this could indicate a possible
pathway," said Dr Chunyuan Fei, from UCLA, one of the study's authors.
Professor
Jørn Olsen, Chair of Department of Epidemiology at UCLA, and the
principle investigator of the study, said that the team is waiting for
further studies to replicate its findings in order to discover whether
PFCs should be added to the list of risk factors for infertility.
EFSA opinion
The
European Food Safety Authority's (EFSA) CONTAM Panel adopted an opinion
on PFOS, PFOA and their salts in February last year, after looking at
several different sources of exposure to the two substances.
With
regard to PFOS, the Panel established a Tolerable Daily Intake (TDI) of
150ng/kg per body weight (bw) per day. The Panel noted that the highest
exposed people within the general population might slightly exceed this
TDI, but considered it unlikely that adverse effects of PFOS were
occurring in the general population.
For
PFOA, the Panel established a TDI of 1.5µg/kg bw per day, which it said
was well above the indicative average and high level human exposure (2
and 6 ng/kg bw respectively). While the Panel considered it unlikely
that adverse effects of PFOA were occurring in the general population,
it did note uncertainties in regards to developmental effects.
And the Panel also recommended that further investigations should be carried out in a number of areas related to PFOS and PFOA.

Changes in serum cortisol and prolactin associated with acupuncture during controlled ovarian hyperstimulation in women undergoi

Melissa — Thu, 29 Jan 2009 15:33:17 -0800

CONCLUSION(S): In this study, there appears to be a beneficial regulation of Cortisol and Prolactin in the Acupuncture group during the medication phase of the IVF treatment with a trend toward more normal fertile cycle dynamics.

Magarelli PC, Cridennda DK, Cohen M. Reproductive Medicine and Fertility Centers, Colorado Springs, Colorado, USA.

OBJECTIVE:
To determine whether changes in serum cortisol (CORT) and PRL are
affected by acupuncture (Ac) in Ac-treated IVF patients. DESIGN:
Prospective cohort clinical study. SETTING: Private practice
reproductive endocrinology and infertility clinic and private practice
acupuncture consortium. PATIENT(S): Sixty-seven reproductive-age
infertile women undergoing IVF. INTERVENTION(S): Blood samples were
obtained from all consenting new infertility patients and serum CORT
and serum PRL were obtained prospectively. Patients were grouped as
controls (IVF with no Ac) and treated (IVF with Ac) according to
acupuncture protocols derived from randomized controlled trials. MAIN
OUTCOME MEASURE(S): Serum levels of CORT and PRL were measured and
synchronized with medication stimulation days of the IVF cycle (e.g.,
day 2 of stimulation, day 3, etc.). Reproductive outcomes were
collected according to Society for Assisted Reproductive Technology
protocols, and results were compared between controls and those
patients treated with Ac.

RESULT(S): CORT levels in Ac group were
significantly higher on IVF medication days 7, 8, 9, 11, 12, and 13
compared with controls. PRL levels in the Ac group were significantly
higher on IVF medication days 5, 6, 7, and 8 compared with controls.

Traditional Chinese medicine and infertility

Lorne Brown — Sun, 06 Jul 2008 18:27:03 -0700

Conclusions: The growing popularity of traditional Chinese medicine used alone or in combination with Western medicine highlights the need to examine the pros and cons of both Western and traditional Chinese medicine approaches. Integrating the principle and knowledge from well characterized approaches and quality control of both traditional Chinese medicine and Western medical approaches should become a trend in existing clinical practice and serve as a better methodology for treating infertility.

Huang ST, Chen AP. Department
of Chinese Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical
Center, Chang Gung Institute of Technology, Taiwan, ROC.
shenteng [at] adm [dot] cgmh [dot] org [dot] tw

PURPOSE OF REVIEW:
The present review gives an overview of the potential use of
traditional Chinese medicine in the treatment of infertility, including
an evidence-based evaluation of its efficacy and tolerance. RECENT
FINDINGS: Recent studies demonstrated that traditional Chinese medicine
could regulate the gonadotropin-releasing hormone to induce ovulation
and improve the uterus blood flow and menstrual changes of endometrium.
In addition, it also has impacts on patients with infertility resulting
from polycystic ovarian syndrome, anxiety, stress and immunological
disorders. Although study design with adequate sample size and
appropriate control for the use of traditional Chinese medicine is not
sufficient, the effective studies have already indicated the necessity
to explore the possible mechanisms, that is, effective dose, side
effect and toxicity of traditional Chinese medicine, in the treatment
of infertility by means of prospective randomized control trial.
SUMMARY: The growing popularity of traditional Chinese medicine used
alone or in combination with Western medicine highlights the need to
examine the pros and cons of both Western and traditional Chinese
medicine approaches. Integrating the principle and knowledge from well
characterized approaches and quality control of both traditional
Chinese medicine and Western medical approaches should become a trend
in existing clinical practice and serve as a better methodology for
treating infertility.

The role of acupuncture in the management of subfertility.

Lorne Brown — Sun, 06 Jul 2008 18:26:15 -0700

CONCLUSION(S): Although acupuncture has gained increasing popularity in the management of subfertility, its effectiveness has remained controversial.

Ng EH, So WS, Gao J, Wong YY, Ho PC. Department of Obstetrics & Gynaecology, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. nghye [at] hkucc [dot] hku [dot] hk Fertil Steril. 2008 Jul;90(1):1-13. Epub 2008 Apr 28 Links

OBJECTIVE: To review systematically the use of acupuncture in the management of subfertility. DESIGN: A computer search was performed via several English and Chinese databases to identify journals relevant to the subject. RESULT(S): The positive effect of acupuncture in the treatment of subfertility may be related to the central sympathetic inhibition by the endorphin system, the change in uterine blood flow and motility, and stress reduction. Acupuncture may help restore ovulation in patients with polycystic ovary syndrome, although there are not enough randomized studies to validate this. There is also no sufficient evidence supporting the role of acupuncture in male subfertility, as most of the studies are uncontrolled case reports or case series in which the sample sizes were small. Despite these deficiencies, acupuncture can be considered as an effective alternative for pain relief during oocyte retrieval in patients who cannot tolerate side effects of conscious sedation. The pregnancy rate of IVF treatment is significantly increased, especially when acupuncture is administered on the day of embryo transfer. CONCLUSION(S): Although acupuncture has gained increasing popularity in the management of subfertility, its effectiveness has remained controversial.

Chinese Herbs increase ATP production and antioxidants

Lorne Brown — Thu, 19 Jun 2008 04:51:08 -0700

Conclusions: Yang tonifying herbs stimulate mitochondrial ATP generation, leading to the enhancement of cellular/mitochondrial antioxidant status, presumably through the intermediacy of ROS. Yin tonifying herbs, which also possess antioxidant properties, are mainly immunomodulatory, thereby boosting weak immune functions and suppressing overreactive or unbalanced immune responses.

Kam Ming Ko¹ and Hoi Yan Leung Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, Chi

Corresponding author. Kam Ming Ko: bcrko [at] ust [dot] hk; Hoi Yan Leung: bclhy [at] ust [dot] hk

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Chinese tonifying herbs such as Herba Cistanche, Ganoderma and Cordyceps,
which possess antioxidant and/or immunomodulatory activities, can be
useful in the prevention and treatment of age-related diseases.
Pharmacological studies on Yang and Yin tonifying herbs suggest that
Yang tonifying herbs stimulate mitochondrial adenosine triphosphate
(ATP) generation, presumably through the intermediacy of reactive
oxidant species, leading to the enhancement of cellular/mitochondrial
antioxidant status. Yin tonifying herbs, however, apart from possessing
antioxidant properties, exert mainly immunomodulatory functions that
may boost a weak immune system and may also suppress overreactive
immune responses. The abilities of Yang and Yin Chinese tonifying herbs
to enhance ATP generation and to exhibit antioxidant and/or
immunomodulatory actions are the pharmacological basis for their
beneficial effects on the retardation of aging.

Background

Aging
is a process of bodily change with time, leading to increased
susceptibility to disease, and ultimately death. Because reactive
oxidant species (ROS) and immune dysfunction are major causes of
age-related diseases [1-3],
the maintenance of antioxidant and immune fitness is a rational
approach to preventive health care. Accumulation of ROS-induced
oxidative damage to DNA, proteins, and other macromolecules has been
regarded as a major endogenous cause of aging [1].
In addition to ROS-mediated cellular damage, aging was found to be
associated with immune senescence, attributable at least partly to the
loss of T lymphocyte functions [2,3].
Such loss increases the prevalence of infectious diseases in the
elderly. With advances in modern medical research techniques, research
on age-related chronic illnesses has become intense, in the quest for
valuable preventive and therapeutic measures. Humans have been making
continuous efforts to fight aging. As Chinese medicine has always
emphasized the prolongation of a healthy lifespan, many Chinese
tonifying herbs have long been used to safeguard health and to delay
the onset of senility.

Under both normal and pathological
conditions, ROS are generated in all cells undergoing aerobic
metabolism, particularly from mitochondria. The cell possesses two
distinct antioxidant defense systems to counteract damaging ROS: (1)
enzymatic antioxidants such as catalase, superoxide dismutase (SOD),
glutathione peroxidase and other related enzymes/molecules, and (2)
non-enzymatic antioxidants such as ascorbic acid (vitamin C),
α-tocopherol (vitamin E) and β-carotene. To achieve optimal antioxidant
fitness, every component of the antioxidant defense system should
function optimally because antioxidants must work together in a
synergistic manner. Chinese tonifying herbs have been shown to possess
both in vitro and in vivo antioxidant activities [4,5].

The
immune system fights against 'foreign invaders' such as bacteria,
viruses, fungi, yeasts and parasites. The humoral and cell-mediated
immune responses show great competence in dealing with intruders.
Moreover, the surveillance function of the immune system tends to
prevent cancers, particularly in old age. However, an overreactive or
imbalanced immune system can cause allergies or autoimmune disorders. A
well-constituted and balanced immune system is thus crucial for
safeguarding health. Chinese tonifying herbs have been shown to
stimulate or suppress the cell-mediated immune response both in vitro and in vivo [6].

The
importance of disease prevention has been recognized by Chinese
medicine through experience accumulated over centuries. Many Chinese
tonifying herbs have long been used for safeguarding health and for
delaying the onset of senility. According to Chinese medicine theories,
tonifying herbs prescribed for various symptoms of ill-health are
generally classified into four categories on the basis of their
health-promoting actions, namely 'Yang-invigorating', the 'Qi-invigorating', the 'Yin-nourishing' and the 'Blood-enriching' herbs [7]. The 'Qi-invigorating'
and 'Blood-enriching' herbs are of Yang and Yin characteristics
respectively. Chinese medicine theories suggest that a balance of Yin
and Yang is essential to sustain optimal body function [8].
From a modern medical perspective, the maintenance of Yin and Yang in
harmony may be described as the attainment of bodily homeostasis. The
long-known antagonistic relationship between parasympathetic and
sympathetic neural activities affords an example of both a phenomenon
well-recognized by Western medicine and the Yin/Yang balance. A recent
psychophysiological investigation in humans revealed an association
between decreased parasympathetic or sympathetic activities with
deficiencies of Yin or Yang respectively [9].

The
theoretical framework of Chinese medicine is based on the Chinese
cultural fabrics and clinical experience, while modern Western medicine
has been established on the basis of laboratory and clinical
investigations [10].
As the two distinct medical systems are complementary, bridging of the
knowledge gap between Chinese and Western medicine is essential for
their integration, in clinical practice, for disease prevention and
treatment. Expounding Chinese medicinal theories in modern scientific
terms to a Western audience facilitates communication between
practitioners of the two systems.

In our earlier studies, we
found that tonifying herbs with Yang or Yin properties were associated
with antioxidant and immunostimulatory activities respectively [4].
Recent studies indicated that only Yang tonifying herbs (not Yin
tonifying herbs) enhanced mitochondrial ATP generation capacity in
mouse hearts [11].
We therefore suggest that Yang tonifying herbs enhance mitochondrial
ATP generation, while Yin tonifying herbs are associated with
immunomodulatory activities. In this mini-review, we summarize the
abilities of Yang and Yin tonifying herbs to enhance ATP generation
capacity, and to potentiate antioxidant and/or immunomodulatory
actions, in an effort to characterize their respective pharmacological
properties.

Enhancement of ATP generation by Yang tonifying herbs

In
Chinese medicinal theories, Yang is a manifestation of body functions
supported by various organs. A 'Yang-invigorating' action therefore
involves the enhancement of bodily functions in general and cellular
activities that consume ATP in particular. The mitochondrion is
responsible for the generation of ATP through oxidative metabolism. To
establish the pharmacological basis of 'Yang-invigorating' action, we
have recently investigated the effect of Yang herbs on ATP generation
capacity in heart homogenates prepared from mice that were pretreated
with methanolic extracts of herbs [11].
Tonifying herbs from other functional categories were examined for
comparison. While Chinese herbs are usually extracted by water for
human oral consumption, water was replaced by methanol in our study for
convenience in the processing and storage of samples. Yang herbs
invariably enhanced myocardial ATP generation, with stimulation ranging
from 20–130%. Herba Cynomorii and Semen Cuscutae were
the most potent herbs examined. By contrast, none of the Yin herbs
enhanced ATP generation; some Yin herbs even suppressed ATP generation
slightly (Table 1).
A preliminary mechanistic study indicated that Yang herbs may speed up
ATP synthesis by increasing mitochondrial electron transport [11].

Table 1

Effect of Yang and Yin tonifying herbs on myocardial ATP generation capacity in mice ex vivo

Correlation between enhancement of ATP generation capacity and antioxidative capacity

Mitochondrial
oxidative phosphorylation generates ROS as byproducts. Highly reactive
chemically, ROS attack cellular structures located near the sites where
ROS are generated. Mitochondrial DNA, proteins, and lipids in the inner
membrane of mitochondria are thus vulnerable to oxidative damage [12], resulting in generalized organelle dysfunction, defective mitochondrial biosynthesis and poor energy metabolism [13].

Under
normal physiological conditions, the mitochondrial antioxidant defense
system adequately handles the potentially detrimental effects of ROS
derived from energy metabolism [14].
When a functional imbalance between ROS levels and antioxidant
concentrations caused by various disease states and/or aging occurs,
age-related disorders such as cancer, cardiovascular diseases, brain
dysfunction, or cataract may occur [15]. Antioxidant supplementation, particularly from herbal extracts, has become a trend in preventive health care.

Using an oxygen radical absorbance capacity assay, Ou et al. recently compared the free radical scavenging (i.e. antioxidant) activities of Yang and Yin herbs [16].
The results indicated that Yin herbs generally possessed higher
antioxidant activities than Yang herbs and that the antioxidant
potencies correlated well with the amounts of total phenolic compounds
in the herbs. The authors suggested an analogy between Yin/Yang balance
and antioxidation/oxidation in energy metabolism. These findings of
higher antioxidant activities in Yin herbs as compared with those in
Yang herbs do not agree with the findings from one of our earlier
studies which showed that most of the Yang herbs possessed a more
potent 1,1-diphenylpicryhydrazyl radical-scavenging action than other
tonifying herbs [4] (Table 2).
Although the use of different herbal extraction methods and distinct
antioxidant assays precludes direct comparison of the two studies, the
discrepancy might be due to the selection of almost completely
different sets of Yin and Yang herbs for testing in the two studies.
Our study focused on herbs used for safeguarding health (i.e. herbs
used for tonifying purposes) (Tables 2, Table 3 of reference [17]). Ou et al.
probably used a selection criterion based on the general Yin and Yang
properties of the herbs instead of their Yin-tonifying and
Yang-tonifying actions [16]. Szeto and Benzie, using the same set of herbs described in Ou et al.
to examine possible protective effects on DNA oxidative damage, found
that the Yang herbs showed an antioxidant effect superior to that of
Yin herbs [5].

Table 2

Antioxidant and immunomodulatory activities of Chinese tonifying herbs

Table 3

Nomenclature and classification of selected Yang and Yin tonifying herbs *

Antioxidant activities of Yang tonifying herbs

Several Yang herbs have been shown to possess antioxidant activities both in vitro and in vivo (Table 4). In vitro free radical-scavenging activities were detected in herbal extracts prepared from Herba Epimedii [4,18], Radix Dipsaci [4,16], Fructus Psoraleae [4], Semen Cuscutae [16], Herba Cistanche [4,16,18], Cortex Eucommiae [19] and Rhizoma Cibotii [4,16]. Aqueous extracts of Rhizoma Drynariae and Cortex Eucommiae were found to inhibit oxidant production from rat osteoblasts [20], and also inhibited biomolecular oxidative damage [21]. Active ingredients (bakuchiol, isobavachin and isobavachalcone) from Fructus Psoraleae inhibited the NADPH-dependent peroxidation of rat microsomal and mitochondrial lipids in vitro [22]. An ethanolic extract of Radix Dipsaci enhanced the antioxidant status of blood and liver in rodents [23] and a Radix Morindae extract increased blood antioxidant enzyme activities in diabetic rats [24]. Phenylethanoids isolated from Herba Cistanche were found to prevent cell damage induced by in vitro and in vivo exposure to carbon tetrachloride in rats [25]. A recent study from our laboratory indicated that pretreatment with the methanolic extract of Herba Cistanche protected against ischemia-reperfusion injury in rat hearts ex vivo and enhanced mitochondrial ATP generation in the rat hearts ex vivo and H9c2 cells in situ.
The ATP-stimulating action was possibly due to enhanced oxidative
phosphorylation caused by increases in the activities of complexes I
and III [26].
As good body function requires a large amount of energy and antioxidant
defense is essential in sustaining mitochondrial ATP production [27],
the antioxidant activities of Yang herbs may safeguard ATP generation,
particularly under conditions of upregulated cellular activities.

Table 4

Antioxidant activities of Yang tonifying herbs

Antioxidant activities of Yin tonifying herbs

Methanolic extracts of both Fructus Ligustri and Herba Ecliptae were found to enhance hepatic glutathione (GSH) regeneration capacity in rats [4,28]. The enhancement of hepatic GSH regeneration capacity by Fructus Ligustri was associated with a hepatoprotective action against carbon tetrachloride toxicity [28]. Activity-directed fractionation of Fructus Ligustri indicated
that the hepatoprotective principle(s) resided mainly in the oleanolic
acid-enriched butanol and chloroform fractions [28].
Moreover, our recent studies showed that both short and long term
pretreatment with oleanolic acid protected against myocardial
ischemia-reperfusion injury in rats [29,30].
It was suggested that the cardioprotection afforded by oleanolic acid
pretreatment was related to the enhancement of mitochondrial
antioxidant mechanism mediated by GSH and α-tocopherol [29].
Both experimental and clinical investigations indicated that the
antioxidant status influenced immunocompetence, particularly under
conditions of stress such as physical exercises or chronic diseases [31]. The antioxidant activities of Yin tonifying herbs may positively influence immunostimulatory activities.

Experimental studies on a 'Yang-invigorating' herbal formula

A 'Yang-invigorating' herbal formula named VI-28 has been shown to produce 'Yang-invigorating' effects [32]
and enhance red cell antioxidant status, particularly Cu-Zn-superoxide
dismutase (SOD) activity, in elderly male human subjects [33]. This herbal formula is comprised of Radix Ginseng, Cornu Cervi, Cordyceps, Semen Allii, Fructus Cnidii, Fructus Evodiae and Rhizoma Laemferiae.
Recently we investigated the effects of long-term VI-28 treatment on
red cell Cu-Zn-SOD activity, mitochondrial functional ability, and
antioxidant levels, in various tissues of rats of both sexes [34].
The results indicated that VI-28 treatment increased red cell Cu-Zn-SOD
activity and mitochondrial ATP generation capacity, increased the
levels of reduced GSH and α-tocopherol, and reduced Mn-SOD activities.
The enhancement of ATP generation by VI-28 increased mitochondrial ROS
production, resulting in the upregulation of mitochondrial antioxidant
mechanism. The VI-28-induced increase in mitochondrial antioxidant
capacity in various tissues was evidenced by a significant reduction in
ROS generation. Given that cellular energy status and mitochondrial ROS
generation are factors critically involved in aging, the dual effect of
'Yang-invigoration' produced by VI-28 may have clinical implications in
the prevention of age-related diseases.

Immunomodulatory activities of Yin tonifying herbs

It
was suggested that the proper functioning of the immune system requires
dynamic interactions between Yang and Yin. And while the
antigen-nonspecific immune response is associated with Yang, the
antigen-specific response is related toYin [35].
One of our earlier studies investigated antioxidant and
immunomodulatory activities in different categories of tonifying herbs.
The results showed that 6 and 7 of a total of 8 Yin herbs tested
potentiated concanavalin A (Con A)-stimulated splenocyte proliferation
(an antigen-specific response) in mice in vitro and ex vivo respectively. By contrast, only 3 of 9 Yang herbs tested showed a similar enhancement of the Con A-stimulated immune response [4] (Table 2).

Among the Yin herbs, the methanolic extract of Fructus Ligustri yielded the most robust immunostimulatory action in mouse splenocytes [4]. Differential extraction of Fructus Ligustri by
solvents of increasing polarity indicated that the immunostimulatory
activity resided mainly in the petroleum ether fraction [36]. Oleanolic acid, an immunomodulatory triterpenoid commonly found in herbs including Fructus ligustri [37,38], was undetectable in this fraction [36]. Currently, activity-directed fractionation of the petroleum ether extract of Fructus Ligustri is
under way in our laboratory. Various immunomodulatory actions of Yin
tonifying herbs, and the active ingredients of the herbs, have been
reported in other studies (Table 5). An aqueous extract of Radix Asparagi was
found to inhibit tissue necrosis factor-α (TNF-α) secretion by
suppressing Interleukin (IL)-2 secretion from astrocytes, implicating
that the extract might exhibit anti-inflammatory activity in the
central nervous system [39]. Both the crude aqueous extract and the two active ingredients (ruscogenin and ophiopogonin D) of Radix Ophiopogonis produced anti-inflammatory effects in rodents [40].
While the aqueous extract inhibited xylene-induced ear swelling and
carrageenan-induced paw edema in mice, it also suppressed
carrageenan-induced pleural leukocyte migration in rats, and the
zymosan-evoked migration of peritoneal total leukocytes and neutrophils
in mice. Treatments with ruscogenin and ophiopogonin D decreased
zymosan-induced peritoneal leukocyte migration in mice and reduced the
phorbol-12-myristate-13 acetate-induced adhesion of HL60 cells to
ECV304 cells [40]. Several sesquiterpenes isolated from Herba Dendrobii were
found to exhibit immunomodulatory activity by exerting comitogenic
effects on Con A and lipopolysaccharide-stimulated mouse splenocytes [41,42]. It has recently been reported that an ethanolic extract of black rice (the fruit of Oryza sativa) showed anti-asthmatic effects in a mouse model [43].
Treatment with the ethanolic extract of black rice reduced the number
of eosinophils in bronchoalveolar lavage fluid, alleviated the airway
hyper-response, and decreased the extent of airway inflammation in
ovalbumin (OVA)-immunized and -aerolized mice challenged with OVA.
Moreover, the ethanolic extract treatment decreased interferon-γ
(INF-γ), IL-4, IL-5 and IL-13 levels in the supernatants of cultured
splenocytes and suppressed the plasma levels of OVA-specific
immunoglobulin (Ig)G, IgG2α, IgG1 and total IgE in OVA-immunized and
-challenged mice [43]. Clinical investigations indicated that intramuscular injection of undiluted Fructus Ligustri extract at a dose of 2–4 ml once or twice daily could prevent leucopenia caused by chemotherapy or radiotherapy. Fructus Ligustri treatment normalized white blood cell counts, thereby increasing tolerance to chemo/radiotherapy [44]. Oral administration of Fructus Ligustri tablets at a daily dose of 50 g equivalence of crude herb was found to ameliorate the symptoms of chronic bronchitis [44]. A herbal formula comprising Fructus Ligustri, Radix Scutellariae, Radix Astragalus and Eupolyphaga et polyphae was found to alleviate symptoms and improve immune function in HIV/AIDS patients [45].

Table 5

Immunomodulatory activities of Yin tonifying herbs

Ganoderma – A 'Fu Zheng' tonifying herb

Ganoderma,
another Yin tonifying herb with immunomodulatory effects, is widely
consumed by the Chinese people who believe that it promotes health and
longevity, lowers the risk of cancer and heart diseases and boosts the
immune system [46]. In Chinese medicine, Ganoderma is regarded as a very potent herb for 'Fu Zheng', a Chinese medicine concept comparable to immunotherapy/immunomodulation in Western medicine. While Ganoderma is
traditionally used to increase the resistance of the body immune system
to pathogens and to restore normal body functions, the herb has now
also been used to decrease the side effects of Western medical
procedures, such as surgery, radiotherapy and chemotherapy which often
weaken the immune system. The anti-cancer/immunomodulatory effects of Ganoderma were associated with triterpenes [47], polysaccharides [48,49] or immunomodulatory proteins [50] through mechanisms involving inhibition of DNA polymerase [51], inhibition of post-translational modification of the Ras oncoprotein [52] or the stimulation of cytokine production [53]. Recent studies on the immunomodulatory activities of Ganoderma indicated that Ganoderma extract
stimulated the proliferation of human peripheral blood mononuclear
cells and raised the levels of mRNAs encoding Th1 and Th2 cytokines in
these cells [54]. Moreover, polysaccharides of Ganoderma activated
mouse splenic B cells and induced these cells to differentiate into
IgM-secreting plasma cells. This process was dependent on the
polysaccharide-mediated induction of Blimp-1, a master regulator
capable of triggering a cascade of gene expression during plasmacytic
differentiation [55]. In human peripheral B lymphocytes, the Ganoderma polysaccharide
fraction enhanced antibody secretion and induced the production of
Blimp-1 mRNA, though it failed to induce lymphocyte differentiation [55].

In addition to immunomodulating activities, Ganoderma possesses in vivo antioxidant potential, another aspect of Yin tonifying action. Treatment with Ganoderma extract was found to enhance the hydroxyl radical scavenging activity of rabbit blood plasma [56,57]. Ganoderma acted by stimulating cellular and mitochondrial SOD activities, thereby enhancing the antioxidant capacity of the body [58]. It was shown that an intraperitoneal injection of Ganoderma extract following a lethal dose of cobalt X-ray radiation caused a marked prolongation of survival time in mice [59]. Pretreatment with Ganoderma extract
also markedly protected against carbon tetrachloride-induced hepatic
damage and the associated impairment in hepatic antioxidant status [60].

Cordyceps – A Yin/Yang tonifying herb

Cordyceps,
a premium Chinese tonifying herb which replenishes the 'kidney' and
soothes the 'lung', is prescribed for the treatment of a host of
disorders, including hyposexualities, hyperglycemia, hyperlipidemia,
asthenia after illness, respiratory diseases, renal disorders, liver
and heart diseases [61]. Cordyceps is
regarded as a tonifying herb with both 'Yin-nourishing' and
'Yang-invigorating' actions. Pharmacological studies have shown that Cordyceps possesses a wide spectrum of biological activities including antioxidation [61-64], immunopotentiation [65-68], anti-tumorigenesis [68-71], anti-inflammation [72] and stimulation of testosterone biosynthesis [73]. We have recently investigated the effects of wild and cultured Cordyceps on Con A-stimulated splenocytes (an in vitro bioassay for Yin tonifying action) and myocardial ATP generation capacity (an ex vivo bioassay for Yang tonifying action) [74]. The results indicated that methanolic extracts of wild and cultured Cordyceps enhanced both the Con A-stimulated splenocyte proliferation in vitro and myocardial mitochondrial ATP generation ex vivo in mice, with no significant difference in potencies when the two types of Cordyceps were
compared. While the immunopotentiating effect was associated with an
increase in IL2 production, the stimulation of myocardial ATP
generation was paralleled by an enhancement in mitochondrial electron
transport. When compared with typical Yin and Yang tonifying herbs (Fructus Ligustri and Herba Cynomorii respectively), Cordyceps was
found to possess both Yin and Yang tonifying actions, with a lower
potency in both modes of action. The observation of both
immunopotentiating and ATP-enhancing activities in Cordyceps extracts further supports the pharmacological basis of Yin and Yang tonifying herbs in Chinese medicine.

Conclusion

Yang
tonifying herbs stimulate mitochondrial ATP generation, leading to the
enhancement of cellular/mitochondrial antioxidant status, presumably
through the intermediacy of ROS. Yin tonifying herbs, which also
possess antioxidant properties, are mainly immunomodulatory, thereby
boosting weak immune functions and suppressing overreactive or
unbalanced immune responses. Cordyceps, highly regarded as a
tonifying herb with a dual action of Yin and Yang, stimulates
mitochondrial ATP generation and enhances cellular immune responses.
Given that impairment in mitochondrial functional ability and
antioxidant status, and a decline in immunocompetence, are believed to
be critically involved in the development of age-related diseases and
the aging process, the abilities of Yang and Yin tonifying herbs to
enhance ATP generation capacity and to produce antioxidant and
immunomodulatory actions are beneficial for safeguarding health and
delaying the onset of senility (Figure 1).
While animal models may be used for testing working hypotheses on Yang
and Yin tonifying actions, clinical studies, using Yang and Yin
tonifying herbs and/or defined chemicals isolated from the herbs or
synthesized in the laboratory, on age-related variations in antioxidant
and immune function, would be of considerable value.

British Medical Journal Meta-Analysis: Acupuncture & IVF

AcuBweb — Mon, 02 Jun 2008 07:43:37 -0700

Conclusion: Canadian Medical Association sent out the following summary to Physicians; Bottom line, Acupuncture administered immediately before and after transfer can increase the rate of clinical pregnancy in women receiving in vitro fertilization. For every 10 woman who received acupuncture, 1 additional pregnancy occurred (number needed to treat = 10).

Manheimer E, Zhang G, Udoff L, et al. Effects of acupuncture on rates of pregnancy and live birth among women undergoing in vitro fertilisation: systematic review and meta-analysis. BMJ 2008;336(7643):545-549.

Study design: Meta-analysis (randomized controlled trials)

Synopsis

To perform this meta-analysis, the researchers searched 4 databases, including the Cochrane Library and the Chinese Biomedical Database, to find randomized controlled trials that compared acupuncture with sham acupuncture or no adjuvant treatment. They also scanned conference proceedings and reference lists of identified research articles (3 studies included in this review were published only in abstract form, although additional information was obtained from the researchers). The authors identified 7 studies evaluating the role of acupuncture on achieving pregnancy following in vitro fertilization in 1366 women (740 whop received acupuncture). Five of these studies also reported the rates of ongoing pregnancy beyond 12 weeks and 4 studies reported live births. Two authors independently selected articles and extracted the data. Their analysis was by intention to treat; that is, the authors included results from women who began the in vitro fertilization process but did not have embryo transfer. The quality of the individual studies was high. There was no evidence of publication bias. All included studies evaluated acupuncture treatment that was administered within a day of embryo transfer and within 3 days following transfer, although all but 1 study performed acupuncture immediately before and immediately after transfer. All but 1 of the studies used the same acupuncture points. The rate of pregnancy in the control groups varied by country; countries vary in the number of embryos that can be transferred and whether high-quality embryos can be selected. Achievement of pregnancy, ongoing pregnancy beyond 12 weeks, and live births were all increased in the acupuncture group. The rate of clinical pregnancy was 32% in the acupuncture group and 27% in the control group (odds ratio = 1.91; 95% CI, 1.39 - 2.64). Using pooled data, 1 additional clinical pregnancy occurred for every 10 women (95% CI, 7 - 17) who received acupuncture rather than sham acupuncture or other control treatment.

Chinese Herbal Medicine for Primary Dysmenorrhea

Lorne Brown — Mon, 26 May 2008 14:34:26 -0700

CONCLUSIONS: The review found promising evidence supporting the use of Chinese herbal medicine for primary dysmenorrhoea

Zhu X, Proctor M, Bensoussan A, Wu E, Smith C.

BACKGROUND: Conventional treatment for primary dysmenorrhoea has a failure rate of 20% to 25% and may be contraindicated or not tolerated by some women. Chinese herbal medicine may be a suitable alternative. OBJECTIVES: To determine the efficacy and safety of Chinese herbal medicine for primary dysmenorrhoea when compared with placebo, no treatment, and other treatment. SEARCH STRATEGY: The Cochrane Menstrual Disorders and Subfertility Group Trials Register (to 2006), MEDLINE (1950 to January 2007), EMBASE (1980 to January 2007), CINAHL (1982 to January 2007), AMED (1985 to January 2007), CENTRAL (The Cochrane Library issue 4, 2006), China National Knowledge Infrastructure (CNKI, 1990 to January 2007), Traditional Chinese Medicine Database System (TCMDS, 1990 to December 2006), and the Chinese BioMedicine Database (CBM, 1990 to December 2006) were searched. Citation lists of included trials were also reviewed. SELECTION CRITERIA: Any randomised controlled trials involving Chinese herbal medicine versus placebo, no treatment, conventional therapy, heat compression, another type of Chinese herbal medicine, acupuncture or massage. Exclusion criteria were identifiable pelvic pathology and dysmenorrhoea resulting from the use of an intra-uterine contraceptive device. DATA COLLECTION AND ANALYSIS: Quality assessment, data extraction and data translation were performed independently by two review authors. Attempts were made to contact study authors for additional information and data. Data were combined for meta-analysis using either Peto odds ratios or relative risk (RR) for dichotomous data or weighted mean difference for continuous data. A fixed-effect statistical model was used, where suitable. If data were not suitable for meta-analysis, any available data from the trial were extracted and presented as descriptive data. MAIN RESULTS: Thirty-nine randomised controlled trials involving a total of 3475 women were included in the review. A number of the trials were of small sample size and poor methodological quality. Results for Chinese herbal medicine compared to placebo were unclear as data could not be combined (3 RCTs). Chinese herbal medicine resulted in significant improvements in pain relief (14 RCTs; RR 1.99, 95% CI 1.52 to 2.60), overall symptoms (6 RCTs; RR 2.17, 95% CI 1.73 to 2.73) and use of additional medication (2 RCTs; RR 1.58, 95% CI 1.30 to 1.93) when compared to use of pharmaceutical drugs. Self-designed Chinese herbal formulae resulted in significant improvements in pain relief (18 RCTs; RR 2.06, 95% CI 1.80 to 2.36), overall symptoms (14 RCTs; RR 1.99, 95% CI 1.65 to 2.40) and use of additional medication (5 RCTs; RR 1.58, 95% CI 1.34 to 1.87) after up to three months of follow-up when compared to commonly used Chinese herbal health products. Chinese herbal medicine also resulted in better pain relief than acupuncture (2 RCTs; RR 1.75, 95% CI 1.09 to 2.82) and heat compression (1 RCT; RR 2.08, 95% CI 2.06 to 499.18). AUTHORS' CONCLUSIONS: The review found promising evidence supporting the use of Chinese herbal medicine for primary dysmenorrhoea; however, results are limited by the poor methodological quality of the included trials.

Cochrane Database Syst Rev. 2008 Apr 16;(2):CD005288.

Source PubMed

Smoking destroys oocytes (egg quality)

Lorne Brown — Fri, 23 May 2008 11:16:07 -0700

Conclusions: The study suggest that smoking and environmental pollution destroys oocytes, turning them into mutants! The research shows how this can lead to early menopause, as the primordial follicles disappear.

Martin M. Matzuk Departments
of Pathology, Molecular and Cellular Biology, and Molecular and Human
Genetics, Baylor College of Medicine, Houston, Texas 77030, USA [dot] mmatzuk [at] bcm [dot] tmc [dot] edu

Polycyclic aromatic hydrocarbons (PAH), found in cigarette smoke and air pollution, interact with the aryl hydrocarbon receptor (Ahr) to cause reproductive defects. Mice lacking either Ahr or the pro-apoptotic protein Bax have an increased number of primordial follicles, and these mutant oocytes are resistant to PAH toxicity. A new study shows that the Bax promoter contains two core Ahr response elements, which are required for PAH stimulation of Bax promoter activity in oocytes. Thus, the toxic effects of PAH in oocytes are mediated directly by Ahr induction of the Bax pathway.
Twenty years ago, Mattison1 showed that PAH xenobiotics, including 2, 3, 7, 8-tetrachlorodibenzo-p-dioxins (TCDD) and benzo(a)pyrene (a potent carcinogen and mutagen in cigarettes), cause oocyte loss. PAH exert their effects through the aryl hydrocarbon receptor (Ahr), a ligand-activated member of the Per-ARNT-Sim (PAS) transcription factor family that also contains a basic helix-loop-helix DNA-binding domain2. Upon ligand binding to its PAS domain, cytoplasmic Ahr translocates to the nucleus, where it dimerizes with the Ahr nuclear translocator and directly activates gene expression. Mice lacking Ahr are viable and can produce offspring, but have smaller livers and many hepatic pathologies3. In addition, they do not respond to TCDD by induction of the cytochrome P450, 1a1, and show only a 25% induction of the cytochrome P450, 1a2, compared with wildtype controls. Thus, induction of these cytochromes by TCDD requires Ahr.

Life and death in the balance. Anti-apoptotic factors (for example, Bclx) support oocyte survival, whereas pro-apoptotic factors (for example, Bax) mediate oocyte destruction. The mouse and human Bax promoters contain consensus DNA binding elements for the aryl hydrocarbon receptor (Ahr). Polycyclic aromatic hydrocarbons (PAH), which are environmental toxins, would shift the life/death oocyte balance by binding to the Ahr, induce Bax expression in oocytes, and lead to oocyte death.
Bob Crimi
Members of the Bcl2 family regulate apoptosis and are found in species as divergent as nematodes (for example, Caenorhabditis elegans) and humans. The Bcl2 and Bclx subgroup is anti-apoptotic, whereas the Bax subgroup is pro-apoptotic. Bcl2-/- mice have kidney, lymphocyte, and hair abnormalities, and half die by six weeks of age4. Bax-/- mice have B- and T-cell hyperplasia, and a block in spermatogenesis leading to male infertility5. On page 355 of this issue, Tiina Matikainen and colleagues6 show a direct link between Ahr and Bax in the regulation of oocyte survival.

Bax and Bclx in ovarian physiology
Between embryonic day 8.5 (E8.5) and E11.5 in the mouse, primordial germ cells migrate over a tortuous route from the allantois along the hindgut and to the genital ridge7. Their number rapidly increases8 from 100 (E8.5) to 3,000 (E11.5) to 22,000 (E13.5). At E13.5, many of the germ cells of the female embryo enter prophase I of meiosis, at which time a significant number undergo apoptosis9. The second major period of germ cell apoptosis in the ovary occurs between postnatal day 7 (P7) and P14 (ref. 9). A similarly dramatic attrition of oocytes occurs between birth and puberty in humans. Only recently have we begun to understand the genetic pathways and molecular mechanisms regulating germ cell apoptosis and survival.

Bax is a pro-apoptotic protein expressed in granulosa cells and oocytes of several mammalian species10. In mice lacking Bax11, there are similar numbers of non-atretic primordial (dormant) or primary (early growing) follicles in the ovaries compared with wildtype controls at P4. In contrast, the numbers of non-atretic primordial and primary follicles are increased significantly at six weeks of age. As a result, Bax-/-mice have a prolonged ovarian lifespan such that 1.5−1.75-year-old females continue to have primordial, primary, and more mature follicles, some of which can be fertilized in vitro and develop into embryos.

Bclx is an anti-apoptotic protein expressed ubiquitously during development. Hennighausen and colleagues12 showed that E12.5−E15.5 Bclx-/- embryos have a decreased number of germ cells due to increased apoptosis—indicating that decreased expression of a critical anti-apoptotic factor (Bclx) shifts the balance in favor of pro-apoptotic factors. Germ cells at E12.5 and E13.5 express Bax, suggesting that it is the putative pro-apoptotic protein. The relationship between Bclx and Bax was proven when Bax-/-Bclx-/- mice were found to have a significantly increased number of follicles at P1, compared with Bclx hypomorphic or wildtype females. Bax-/-Bclx-/- females are also fertile, in contrast with Bclx hypomorphs. Thus, during embryogenesis or postnatal life, anything that alters the balance towards pro-apoptotic Bax—including 'reproductive toxins'—would cause increased oocyte loss.

A link between Ahr and Bax
Ahr protein is present in granulosa cells and oocytes at all follicle stages13, suggesting that signaling through the receptor may have a role in ovarian follicle development. Ovaries of Ahr-/- mice13, 14 have a twofold increase in the number of primordial follicles at P2−P4. Interestingly, the number of antral follicles at eight weeks is decreased. These findings indicate that, like Bax ablation, Ahr deficiency helps to maintain oocytes.

Matikainen and colleagues6 demonstrate why the Bax-/- and Ahr-/- ovarian phenotypes are similar. Analysis of the 5' region of the mouse Bax promoter reveals two consensus Ahr response elements2 (GCGTC) in close proximity to one another. Four core response elements are also present in the human BAX promoter. When the nucleotide three bases downstream of the response element is an adenine residue, dioxin (an environmental toxin) is able to activate the gene. In the mouse, the nucleotides three bases downstream of the two response elements are guanine and cytosine, suggesting that dioxin cannot activate Bax. Indeed, mouse oocytes are normally insensitive to dioxin, and oocyte microinjection experiments with a construct containing the wildtype Bax promoter confirm that dioxin is ineffective at induction. Furthermore, mutation of these critical downstream nucleotides to adenine renders the promoter responsive to dioxin. Thus, two nucleotides in the Bax promoter would seem to be the sole 'protection' against damage mediated by dioxin.

Matikainen et al.6 further show the effects of the PAH 9,10-dimethylbenz(a)antracene (DMBA) on oocytes and on Bax levels (see figure). Intraperitoneal delivery of DMBA causes a 72% increase in Bax mRNA levels after 24 hours, and a concomitant increase in Bax protein in oocytes. Treatment with DMBA or a DMBA metabolite also leads to a decrease in the number of non-apoptotic oocytes in cultured wildtype mouse ovaries. However, treatment of AhR- or Bax-deficient ovaries with the potent DMBA metabolite has no effect on the number of non-apoptotic oocytes of primordial follicles, confirming that the Ahr-Bax pathway is required for PAH-induced cell death. Finally, DMBA has a similar effect on human ovarian cortical tissue that is grafted subcutaneously into immunodeficient mice.

As the world's population increases, the consumption of fossil fuels and the production of air pollution will also rise. Aside from the risk of global warming, the generation of PAH and other environmental toxins will continue to cause more health problems. Likewise, there is an increased risk of PAH-related reproductive and developmental defects due to the rising incidence of smoking in young women15. We now know that these toxic PAH compounds signal through a Ahr/Bax-regulated pathway to cause their destructive effects on oocytes. It will be important to identify the endogenous ligand that binds to the Ahr. This would provide a potential means to prevent oocyte loss and also to prolong the reproductive lifespan of human females.

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REFERENCES

PCOS insulin and weight reduction

Lorne Brown — Sun, 18 May 2008 05:59:45 -0700

Conclusions: stating that weight reduction is the most effective way of addressing the underlying metabolic issueassociated with PCOS

http://www.bmj.com/cgi/content/full/317/7154/329 This is from a BMJ article

Good evidence supports the hypothesis that decreased peripheral insulin sensitivity and consequent hyperinsulinaemia are pivotal in the pathogenesis of polycystic ovarian syndrome.5 Peripheral insulin resistance is most evident in overweight patients: obesity and polycystic ovarian syndrome each seem to have a separate and synergistic relation with insulin resistance.5 The exact mechanism(s) for insulin resistance is uncertain, but a post-receptor defect in adipose tissue has been identified.5 Despite insulin resistance in adipose and skeletal muscle, the ovary remains relatively sensitive to insulin, and both insulin and insulin-like growth factor 1 have stimulatory effects on thecal androgen production.9 In fact, some lean women with polycystic ovarian syndrome, who may not have insulin resistance and therefore hyperinsulinaemia, may show enhanced ovarian sensitivity to insulin. Figure 1 shows how the relative excess of insulin or enhanced ovarian sensitivity to insulin, in combination with an elevated luteinising hormone concentration, brings about thecal hyperplasia, increased androgen secretion, arrest of follicular development, and therefore anovulation along with menstrual disturbance.

Insulin also acts on the liver to inhibit the production of sex hormone binding globulin and insulin-like growth factor 1 binding protein. A reduction in sex hormone binding globulin leads to an increase in the biologically available free testosterone. Thus, insulin resistance not only increases secretion of ovarian androgens but also promotes an increase in the proportion of free (active) hormone. Similarly, inhibition of production of insulin-like growth factor 1 binding protein results in an increased concentration of circulating free insulin-like growth factor 1, further enhancing ovarian androgen production.10
Current consensus suggests that the ovary is the principal site of excess androgen production, but some women with polycystic ovarian syndrome may have an adrenal contribution to the increased androgen production. The mechanisms for this remain obscure and are almost certainly multifactorial.

Insulin resistance
As the principal underlying defect in polycystic ovarian syndrome seems to be insulin resistance, the most appropriate treatment for all clinical presentations may be one that specifically addresses this problem.
Weight reduction has multiple benefits for obese women with polycystic ovarian syndrome.24 The resultant reduction in insulin resistance corrects the hormonal imbalance, promotes ovulation and regular menses, and improves the metabolic consequences of the disorder. Weight loss should therefore be encouraged, but it seems to be hard to achieve for this group of patients.

Insulin sensitising agents ---Recent trials have investigated the effect of such agents on polycystic ovarian syndrome. 16 17 24-33 Metformin, a biguanide often used in non-insulin dependent diabetes, has been the most commonly used. Troglitazone, a thiazolidinedione that improves muscle insulin sensitivity, has also been studied 17 27 but has recently been removed from the market because of adverse effects on hepatic function. Trials to date have included only small numbers of subjects, but results have been promising, with most showing reductions in concentrations of fasting serum insulin, androgen, and luteinising hormone. 16 17 26 28 29 31-33 In addition, circulating concentrations of sex hormone binding globulin increased, resulting in less bioactively available testosterone. Preliminary evidence indicates that treatment of obese women with polycystic ovarian syndrome with metformin restores regular menstrual cycles and ovulation. 26 30-32 Whether insulin sensitising agents can modify the vascular risk factors associated with the syndrome remains to be seen, but reductions in Lp (a) lipoprotein and plasminogen activator inhibitor 1 have been observed. 16 17 Additionally, some studies have reported that treated subjects have shown some weight loss despite continuation of their normal diet and lifestyle, 16 26 and others have demonstrated a reduction in central obesity. 26 29 33

Thus, treatments targeting the key factor in the disorder may not only resolve the gynaecological problems with which the syndrome presents, but also reduce the risk of vascular disease in later life. There is now an urgent need for randomised, placebo controlled trials to assess the potential benefits of these treatments for women's health.

linking severe genital herpes leading to infertility, recurrent pregnancy loss and IVF failures

Lorne Brown — Sat, 17 May 2008 08:48:32 -0700

Conclusions: very high levels of inflammatory markers in cervix and serum during severe genital herpes confirm an important role of HSV in genital inflammation, cervical and endometrial pathology, and allow to consider genital herpes as an inflammatory process.

a research study linking severe genital herpes (more than 7 outbreaks a
year) may be the reason of infertility, recurrent pregnancy loss and
IVF failures. How Chinese medicine can help reverse this trend.

Author(s):

Shurshalina A.V., Marchenko L.A., Sukhikh G.T.

Publisher:

European Society of clinical microbiology and infectious diseases

Date Published:

April 2-5, 2005

Research:

Objectives:

Severe genital herpes may be the reason of infertility, recurrent pregnancy loss and IVF failures.

Methods:

103
women (mean age 30.8 ± 0.82) with severe genital herpes (mean
recurrence per year 7.5 ± 0.6) were included in study. We tested
cervical samples for cytokines (IL-6, IL-10, TNF-alfa, IFN-gamma) and
serum samples for CD69+, CD25+ and HLA-DR+ during recurrence, remission
and after 8-month Valaciclovir treatment in the dose of 500 mg per day.
Control group was ten healthy women without genital herpes and HSV
antibodies G and M in serum.

Results:

During herpes
recurrence, the local levels of TNF-alfa increased twice and 8 times as
much as compared to remission and the controls, IFN-gamma – 1.5 and 2.3
times, CD69+ – 1.4 and 3.3 times, CD25+ – 1.4 and 2.5 times, HLA-DR+ –
1.6 .and 2.5 times (p < 0.05). IL-10 decreased 4 and 3.3 times as
less. After Valaciclovir treatment, the cervical levels of TNF-alfa
decreased by 60%, CD69+ – 26%, HLA-DR+ – 23.6% (p < 0.05).

Conclusion:

very
high levels of inflammatory markers in cervix and serum during severe
genital herpes confirm an important role of HSV in genital
inflammation, cervical and endometrial pathology, and allow to consider
genital herpes as an inflammatory process.

Study on Treatment of polycystic ovarian syndrome with Infertility by combined therapy of Chinese herbal medicine and compound c

Lorne Brown — Fri, 16 May 2008 14:39:21 -0700

Conclusion: Using combined therapy of TCM and composite CPA followed by ovulation promoting agents of TCM and WM to treat patients of non-obesity PCOS could relieve the clinical symptoms, improve the abnormal blood level of sex hormones and significantly elevate the pregnancy rate.

Objective: To evaluate the effect of combined therapy of Chinese herbal medicine and compound cyproterone acetate (CPA) in treating non-obesity polycystic ovarian syndrome (PCOS) and to explore its mechanism in improving withdrawal ovulation.Methods: Eighty-six patients of non-obesity PCOS, typed as Shen-deficiency with blood stasis Syndrome or Shen-deficiency with Phlegm-Dampness Syndrome by Syndrome Differentiation in traditional Chines medicine, were randomly divided into three groups: (1) The TCM group (n=26) was treated with Chinese drugs for 6 menstrual cycles; (2) The western medicine (WM) group (n=30) was treated with 1 tablet of CPA for 21 days, with the treatment beginning from the 5th day of menstruation. The treatment was given for 3 menstrual cycles by repetitious medication, which stopped and restarted on the 5th day of withdrawal bleeding. Then the ovulation promoting therapy was applied by using clomifene citrate and human chorionic gonadotropin (CC/hCG) for 3 menstrual cycles; (3) The TCM-WM group (n=30) was treated with the medications used for the above two groups. The menstrual cycle, the volume and duration of the menstruation, as well as the improvement of acne and pilosis [Ferrinian-Gallway (F-G) scoring] were observed after 3 cycles ended. Moreover, condition of ovulation was monitored by B-ultrasonography at the 4th-6th cycle and status of pregnancy was observed.

Results: Compared with before treatment, the blood level of luteinizing hormone (LH) and testosterone (T) in all 3 groups after treatment significantly decreased (P<0.05), with its ratio to follicle-stimulating hormone (LH/FSH) recovered to normal, but without markedly change in levels of FSH, estradiol (E2) and prolactin (PRL). The menstrual cycle in most patients got regular and acne significantly alleviated (P<0.05), and the improvement of infrequent menstruation and acne was better in the WM group and the TCM-WM group than that in the TCM group, but pilosis showed no significant improvement in all three groups. The periodical ovulation rate in the TCM-WM group (73.1%) and the WM group (68.3%) was significantly higher than that in the TCM group (40%). The pregnancy rate in the TCM-WM group (53.8%) was significantly higher than that in the other two groups (26.1% and 25% respectively, all P<0.05).

Protective effect of zuogui pill on ovarian autoimmune injury

Lorne Brown — Fri, 21 Mar 2008 13:18:03 -0700

CONCLUSION: ZGP (Chinese herbal formula) can improve immune inflammatory injury of ovary, and shows therapeutic effect on POF.

Zhu L, Luo SP, Xu LM. Department of TCM, Southern Medical University, Guangzhou. zhuling20012001 [at] yahoo [dot] com

OBJECTIVE:
To probe the effect of Zuogui pill (ZGP), a Chinese compound recipe for
tonifying Shen, on ovarian function in mice with premature ovarian
failure (POF). METHODS: BALB/C female mice model of POF was established
by multiple sites subcutaneous injection of ovarian antigen elicited
with ovarian tissue of SD female rats, and treated with ZGP at
different time points in the modeling, with prednisone as positive
control. The levels of follicle-stimulating hormone (FSH) and estradiol
(E2) in peripheral blood were measured with radioimmunoassay, and
ovarian antibody (AoAb) was determined by enzyme linked immunosorbent
assay. The mRNA expression of ovarian growth and differentiation
factor-9 was detected with in situ hybridization. RESULTS: POF model
mice manifested such abnormalities as increased FSH, decreased E2, and
positive AoAb in peripheral blood, with lymphocytes infiltration in
ovarian mesanchyma, reduction of GDF-9 mRNA positive oocytes, and
decrease of growing and mature follicles. ZGP could reduce the increase
of FSH, increase the level of E2, inhibit the production of AoAb, raise
the GDF-9 mRNA positive cells of oocytes, increase the number of
growing and mature follicles. The clinical efficacy was more
significant in early stage than in advanced stage. CONCLUSION: ZGP can
improve immune inflammatory injury of ovary, and shows therapeutic
effect on POF.