Folate intake and ovarian reserve among women attending a fertility center.

OBJECTIVE: To examine the association between dietary folate intake and antral follicle count (AFC) among women seeing treatment for infertility. DESIGN: Cohort study. SETTING: Academic fertility center. PATIENTS: A total of 552 women attending the Massachusetts General Hospital Fertility Center (2007-2019) who participated in the Environment and Reproductive Health Study. INTERVENTIONS: None. Folate intake was measured with a validated food frequency questionnaire at study entry. Multivariable Poisson regression models with robust standard errors were used to estimate the association of folate intake with AFC adjusting for calorie intake, age, body mass index, physical activity, education, smoking status, year of AFC, and intakes of vitamin B12, iron, and vitamin D. Nonlinearity was assessed with restricted cubic splines. MAIN OUTCOME MEASURE: AFC as measured by transvaginal ultrasonography as part of routine care. RESULTS: Among the 552 women (median age, 35.0 years; median folate intake, 1,005 µg/d), total and supplemental folate intake had a significant nonlinear relationship with AFC. There was a positive linear association with AFC up to approximately 1,200 µg/d for total folate intake and up to 800 µg/d for supplemental folate intake; however, there was no additional benefit of higher folate intakes. The magnitude of the association was modest; for example, the predicted adjusted difference in AFC between a woman consuming 400 vs. 800 µg/d of supplemental folate was approximately 1.5 follicles. CONCLUSION: Higher intake of folate, particularly from supplements, was associated with modestly higher ovarian reserve as measured by AFC among women attending a fertility center. CLINICAL TRIAL REGISTRATION NUMBER: This trial was registered at clinicaltrials.gov as NCT00011713.

Decline in anti-Müllerian hormone concentrations following radioactive iodine treatment in women with differentiated thyroid cancer: A systematic review and meta-analysis.

AIM: Radioactive iodine (RAI) is frequently used as adjuvant therapy in patients with differentiated thyroid cancer (DTC). However, its effect on ovarian reserve has not been fully elucidated, with studies yielding inconsistent results. The aim of this study was to systematically review and meta-analyze the best available evidence regarding the effect of RAI on ovarian reserve in premenopausal women with DTC. METHODS: A comprehensive literature search was conducted in PubMed, Cochrane and Scopus, through to December 6th, 2020. Data were expressed as weighted mean difference (WMD) with a 95% confidence interval (CI). The I2 index was used to assess heterogeneity. RESULTS: Four prospective studies were included in the qualitative and quantitative analysis. Anti-Müllerian hormone (AMH) concentrations decreased at three (WMD -1.66 ng/ml, 95% CI -2.42 to -0.91, p<0.0001; I2 0%), six (WMD -1.58, 95% CI -2.63 to -0.52, p=0.003; I2 54.7%) and 12 months (WMD -1.62 ng/ml, 95% CI -2.02 to -1.22, p<0.0001; I2 15.5%) following a single RAI dose compared with baseline (three studies; n=104). With respect to follicle-stimulating hormone (FSH) concentrations, no difference was observed at six (WMD +3.29 IU/l, 95% CI -1.12 to 7.70, p=0.14; I2 96.8%) and 12 months (WMD +0.13 IU/l, 95% CI -1.06 to 1.32, p=0.83; I2 55.2%) post-RAI compared with baseline (two studies; n=83). No data were available for antral follicle count. CONCLUSIONS: AMH concentrations are decreased at three months and remain low at 6 and 12 months following RAI treatment in women with DTC. No difference in FSH concentrations post-RAI is observed.

Addressing the role of 11ß-hydroxysteroid dehydrogenase type 1 in the development of polycystic ovary syndrome and the putative therapeutic effects of its selective inhibition in a preclinical model.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common metabolic and endocrine disorder among reproductive-age women, and the leading cause of anovulatory infertility. 11ß-hydroxysteroid dehydrogenases-1 (11ß-HSD1) catalysing the conversion of inactive cortisone to active cortisol plays a crucial role in various metabolic diseases. However, whether 11ß-HSD1 is associated with the pathogenesis of PCOS and whether 11ß-HSD1 can be a treating target of PCOS remain unknown. METHODS: This study was first designed to explore the role of 11ß-HSD1 in PCOS development and the effect of selective 11ß-HSD1 inhibitor administration on PCOS treatment. Follicular fluid and granulosa cells (GCs) were collected from 32 non-PCOS patients and 37 patients with PCOS to measure cortisol and 11ß-HSDs levels. Female Sprague-Dawley rats (3-week-old) were injected with dehydroepiandrosterone (DHEA) to induce PCOS and their ovaries were collected to measure the abundance of corticosterone (CORT) and 11ß-HSDs. To determine the role of 11ß-HSD1 in PCOS development, we overexpressed 11ß-HSD1 in the ovaries of female rats (5-week-old) or knocked down the expression of 11ß-HSD1 in the ovaries from PCOS rats via lentivirus injection. After lentivirus infection, the body weights, ovarian weights, estrous cycles, reproductive hormones and morphology of the ovary were analysed in rats from different experimental groups. Then to figure out the translational potential of the selective 11ß-HSD1 inhibitor in treating PCOS, PCOS rats were treated with BVT.2733, a selective 11ß-HSD1 inhibitor and a cluster of PCOS-like traits were analysed, including insulin sensitivity, ovulatory function and fertility of rats from the Control, PCOS and PCOS+BVT groups. Rat ovarian explants and human GCs were used to explore the effect of CORT or cortisol on ovarian extracellular matrix remodelling. RESULTS: The elevated expression of 11ß-HSD1 contributed to the increased cortisol and corticosterone (CORT) concentrations observed in the ovaries of PCOS patients and PCOS rats respectively. Our results showed that ovarian overexpression of 11ß-HSD1 induced a cluster of PCOS phenotypes in rats including irregular estrous cycles, reproductive hormone dysfunction and polycystic ovaries. While knockdown of ovarian 11ß-HSD1 of PCOS rats reversed these PCOS-like changes. Additionally, the selective 11ß-HSD1 inhibitor BVT.2733 alleviated PCOS symptoms such as insulin resistance (IR), irregular estrous cycles, reproductive hormone dysfunction, polycystic ovaries, ovulatory dysfunction and subfertility. Moreover, we showed that cortisol target ovarian insulin signalling pathway and ovarian extracellular matrix (ECM) remodelling in vivo, in ovarian explants and in GCs. CONCLUSION: Elevated 11ß-HSD1 abundance in ovarian is involved in the pathogenesis of PCOS by impairing insulin signalling pathway and ECM remodelling. Selective inhibition of 11ß-HSD1 ameliorates a cluster of PCOS phenotypes. Our study demonstrates the selective 11ß-HSD1 inhibitor as a novel and promising strategy for the treatment of PCOS.

Does coenzyme Q10 supplementation improve fertility outcomes in women undergoing assisted reproductive technology procedures? A systematic review and meta-analysis of randomized-controlled trials.

OBJECTIVE: Increased oxidative stress has been identified as a pathogenetic mechanism in female infertility. However, the effect of specific antioxidants, such as coenzyme Q10 (CoQ10), on the outcomes after assisted reproductive technologies (ART) has not been clarified. The aim of this study was to systematically review and meta-analyze the best available evidence regarding the effect of CoQ10 supplementation on clinical pregnancy (CPR), live birth (LBR), and miscarriage rates (MR) compared with placebo or no-treatment in women with infertility undergoing ART. METHODS: A comprehensive literature search was conducted in PubMed (MEDLINE), Cochrane, and Scopus, from inception to March 2020. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). The I2 index was employed for heterogeneity. RESULTS: Five randomized-controlled trials fulfilled eligibility criteria (449 infertile women; 215 in CoQ10 group and 234 in placebo/no treatment group). Oral supplementation of CoQ10 resulted in an increase of CPR when compared with placebo or no-treatment (28.8% vs. 14.1%, respectively; OR 2.44, 95% CI 1.30-4.59, p = 0.006; I2 32%). This effect remained significant when women with poor ovarian response and polycystic ovarian syndrome were analyzed separately. No difference between groups was observed regarding LBR (OR 1.67, 95% CI 0.66-4.25, p = 0.28; I2 34%) and MR (OR 0.61, 95% CI 0.13-2.81, p = 0.52; I2 0%). CONCLUSIONS: Oral supplementation of CoQ10 may increase CPR when compared with placebo or no-treatment, in women with infertility undergoing ART procedures, without an effect on LBR or MR.

Ulmus minor bark hydro-alcoholic extract ameliorates histological parameters and testosterone level in an experimental model of PCOS rats.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common and multifactorial disease associated with female factor infertility. Ulmus minor bark (UMB) is one of the medicinal plants used in Persian folklore as a fertility enhancer. In the current study, we aimed to elucidate the effect of UMB hydro-alcoholic extract on histological parameters and testosterone condition in an experimental model of PCOS rats. METHODS: Thirty female rats were randomly divided into five groups: (1) control, (2) vehicle, (3) PCOS/50 mg [6 mg/kg dehydroepiandrosterone (DHEA) + 50 mg/kg UMB hydro-alcoholic extract], (4) PCOS/150 mg (6 mg/kg DHEA + 150 mg/kg UMB hydro-alcoholic extract), and (5) PCOS (6 mg/kg DHEA). All interventions were performed for 21 days. Afterwards, stereological analysis was done for determination of ovarian volume and follicle number. The serum level of testosterone was measured by ELISA kit. RESULTS: UMB hydro-alcoholic extract improved the total number of the corpus luteum in the treatment groups when compared to the PCOS group (p<0.05). PCOS/150 mg and PCOS/50 mg groups showed significantly lower total number of the primordial, primary, and secondary follicles as well as testosterone level compared to the PCOS group (p<0.05). The total number of antral follicles and volume of ovary did not differ significantly between groups. CONCLUSION: UMB extract may be an effective and good alternative in improving PCOS histo-logical and testosterone disturbances although further studies are warranted to confirm the safety of UMB plant in human.

Can Panax Ginseng protect against fertility disorders in hypothyroid female albino rats?

Hypothyroidism is an endocrine disorder due to decreased thyroid hormone production. This endocrine disorder significantly affects the menstrual cycle and fertility. The aim of this present study was to assess the efficacy of Panax ginseng, one of traditional Chinese medicine, in ameliorating the gonadal hormonal dysfunction and lowering oxidative stress accompanied with hypothyroidism in adult female albino rats. After confirming regularity of the oestrus cycle in the female rats in this study, hypothyroidism was induced by using daily 5.0 mg kg-1 oral dose of Neo-mercazole. The hypothyroid rats were randomly grouped into two groups; hypothyroid group (H): did not received any treatment, group II (H+G) was treated with Panax ginseng extract for one months after hypothyroidism induction. Another two groups were included in the study, a negative control group (Euthyroid group) and a positive control group; received Panax ginseng extract only. Hypothyroidism resulted in irregularity of oestrus cycle accompanied with decrease in luteinizing hormone (LH), follicular stimulating hormone (FSH) and estradiol (E2), while prolactin (PRL), progesterone (P) and testosterone (T) hormone were significantly elevated. Hypothyroidism elevated capsae-3 and 8OH-deoxy guanosine expression and increased secretion of corticosterone and ERK1/2. This study showed that Panax ginseng improved hypothyroid-induced deterioration in trophic and gonadal hormones through free radicals' scavenger.

Therapeutic Role of Green Tea Polyphenols in Improving Fertility: A Review.

Sperm cells are highly sensitive to reactive oxygen species (ROS), which are produced during cellular oxidation. In normal cell biology, ROS levels increase with a decreasing antioxidant response, resulting in oxidative stress which threatens sperm biology. Oxidative stress has numerous effects, including increased apoptosis, reduced motion parameters, and reduced sperm integrity. In this regard, green tea polyphenols (GrTPs) have been reported to possess properties that may increase the quality of male and female gametes, mostly via the capability of catechins to reduce ROS production. GrTPs have antioxidant properties that improve major semen parameters, such as sperm concentration, motility, morphology, DNA damage, fertility rate, and gamete quality. These unique properties of green tea catechins could improve reproductive health and represent an important study area. This exploratory review discusses the therapeutic effects of GrTPs against infertility, their possible mechanisms of action, and recommended supportive therapy for improving fertility in humans and in animals.

Protective effect of alpha-lipoic acid in methotrexate-induced ovarian oxidative injury and decreased ovarian reserve in rats.

To determine whether the possible oxidative effect of methotrexate (Mtx) on ovary and to evaluate the effectiveness of alpha lipoic acid (ALA), which may be useful in many oxidative stress models. Thirty-two female Wistar-albino rats were randomly divided into four groups; control group, alpha lipoic acid group (ALA 100 mg/kg, 10 days), multiple dose Mtx group (Mtx 1 mg/kg 1, 3, 5, 7 days) and Mtx and ALA group (Mtx 1 mg/kg 1, 3, 5, 7 days and ALA 100 mg/kg, 10 days). Serum total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI), tumor necrosis factor-alpha (TNF-α), tissue malondialdehyde (MDA) and activities of glutathione peroxidase (GSH-Px) and catalase (CAT) and anti-Mullerian hormone (AMH) and total ovarian follicle count were evaluated. Mtx administration caused a significant decrease in TAS, a significant increase in TOS and OSI, a significant increase in MDA levels and a decrease in GSH-Px and CAT activity. Moreover the proinflammatory cytokine (TNF-α) was increased in the Mtx group. And AMH values and total follicle count were significantly decreased in Mtx group. However, ALA treatment reversed biochemical results and AMH levels and total follicle count. Alpha lipoic acid ameliorates methotrexate induced oxidative damage of ovarian in rats.

The effect of FT500 Plus(®) on ovarian stimulation in PCOS women.

Both oxidative stress and polycystic ovary syndrome have been involved in several aspects of female reproduction. In this retrospective observational study, the outcome of controlled ovarian stimulation and follicular microenvironment of twenty-five women affected by PCOS (Group A) have been explored, evaluating the effects of myo-inositol in association with antioxidant activities (FT500 Plus(®)). Twenty-five untreated-PCOS women (Group B) with similar characteristics served as control group. Although there was no difference in ovarian volume at time zero, this parameter was significantly smaller at the 5-month follow-up in the Group A (11.1±0.9 versus 13.5±1; P=0.0001). Group A showed a significant increase in the number of MII oocytes (6.3±2.5 versus 4.5±2; P=0.03) and glutathione peroxidase activity in follicular fluid (15.4±6.2 versus 11±2.2; P=0.04). FT500 Plus(®) may be considered in PCOS patient for improving oocyte quality.

Prevalence & factors associated with chronic obstetric morbidities in Nashik district, Maharashtra.

BACKGROUND & OBJECTIVES: In India, community based data on chronic obstetric morbidities (COM) are scanty and largely derived from hospital records. The main aim of the study was to assess the community based prevalence and the factors associated with the defined COM--obstetric fistula, genital prolapse, chronic pelvic inflammatory disease (PID) and secondary infertility among women in Nashik district of Maharashtra State, India. METHODS: The study was cross-sectional with self-reports followed by clinical and gynaecological examination. Six primary health centre areas in Nashik district were selected by systematic random sampling. Six months were spent on rapport development with the community following which household interviews were conducted among 1560 women and they were mobilized to attend health facility for clinical examination. RESULTS: Of the 1560 women interviewed at household level, 1167 women volunteered to undergo clinical examination giving a response rate of 75 per cent. The prevalence of defined COM among 1167 women was genital prolapse (7.1%), chronic PID (2.5%), secondary infertility (1.7%) and fistula (0.08%). Advancing age, illiteracy, high parity, conduction of deliveries by traditional birth attendants (TBAs) and obesity were significantly associated with the occurrence of genital prolapse. History of at least one abortion was significantly associated with secondary infertility. Chronic PID had no significant association with any of the socio-demographic or obstetric factors. INTERPRETATION & CONCLUSIONS: The study findings provided an insight in the magnitude of community-based prevalence of COM and the factors associated with it. The results showed that COM were prevalent among women which could be addressed by interventions at personal, social and health services delivery level.

Changes in receptivity epithelial cell markers of endometrium after ovarian stimulation treatments: its role during implantation window.

BACKGROUND: To compare the expression of receptivity markers in epithelial and stromal cells in the endometrium of ovulatory women and infertile with hypothalamic pituitary dysfunction (HPD), untreated or treated with clomiphene citrate (CC), or with recombinant follicle stimulating hormone (rFSH). METHODS: Twelve control ovulatory and 32 anovulatory women, 22 of whom received ovulation induction with CC (n = 12) or rFSH (n = 10). Endometrial biopsies were obtained during the mid-secretory phase. Hormonal secretion was measured by chemiluminescence immunoassay, endometrial dating and cellular expression and distribution of receptivity proteins were evaluated by quantitative immunohistochemistry. RESULTS: CC or rFSH treatments, modified the expression of epithelial receptivity markers, such as Glycodelin A, beta-catenin, CD166/ALCAM and IGF-1R, but not in stromal markers. Also, a change in their cell distribution was observed. CONCLUSIONS: Treatment of infertile women with HPD modified the expression and distribution of receptivity markers in the mid-secretory phase of the endometrium in epithelial but not stromal cells, which can help to explain changes in the receptivity of the endometrium during treatments and suggest an important role of these cells in the receptivity window.

Knockdown of hypothalamic RFRP3 prevents chronic stress-induced infertility and embryo resorption.

Whereas it is well established that chronic stress induces female reproductive dysfunction, whether stress negatively impacts fertility and fecundity when applied prior to mating and pregnancy has not been explored. In this study, we show that stress that concludes 4 days prior to mating results in persistent and marked reproductive dysfunction, with fewer successful copulation events, fewer pregnancies in those that successfully mated, and increased embryo resorption. Chronic stress exposure led to elevated expression of the hypothalamic inhibitory peptide, RFamide-related peptide-3 (RFRP3), in regularly cycling females. Remarkably, genetic silencing of RFRP3 during stress using an inducible-targeted shRNA completely alleviates stress-induced infertility in female rats, resulting in mating and pregnancy success rates indistinguishable from non-stress controls. We show that chronic stress has long-term effects on pregnancy success, even post-stressor, that are mediated by RFRP3. This points to RFRP3 as a potential clinically relevant single target for stress-induced infertility.

Clinical observations of sequential therapy with Chinese medicine and hysteroscopic mechanical stimulation of the endometrium in infertile patients with repeated implantation failure undergoing frozen-thawed embryo transfer.

OBJECTIVES: To investigate the clinical effect of sequential therapeutic intervention Yupei Qisun [compensating for weakness by invigorating Kidney (Shen) and Spleen (Pi) in advance] in Chinese medicine (CM) and hysteroscopic endometrial mechanical stimulation on the treatment of infertile patients with repeated implantation failure (RIF); and to study the differences in patients' endometrial thickness and type on the day of embryo transfer, serum hormone levels on embryo transfer day and clinical pregnancy outcomes. METHODS: In the clinical study, 168 frozen-thawed embryo transfer (FET) cycles for couples with RIF conforming to the research protocol were randomly divided into three groups: a CM group with 56 cycles (CM combined with FET), a hysteroscopy group with 55 cycles (hysteroscopic endometrial mechanical stimulation), and a control group with 57 cycles (conventional FET). Differences in endometrial thickness on the embryo transfer day, levels of serum estradiol (E2) and progesterone (P) on the embryo transfer day, the E2/P ratio on the embryo transfer day, biochemical and clinical pregnancy rates, implantation rate, abnormal pregnancy rate and other indices were compared among the three groups. RESULTS: Endometrial thickness, E2 and P levels, and the E2/P ratio on embryo transfer day and other factors had no significant differences among groups. The biochemical pregnancy, clinical pregnancy, and implantation rates of the CM and hysteroscopy groups were significantly higher than the control group (P<0.05), and there were no significant differences between these two groups. The abnormal pregnancy rate had no significant difference among the three groups. CONCLUSIONS: Sequential therapy of Yupei Qisun could significantly improve the clinical outcomes of rif-fet cycles, being equivalent to hysteroscopic endometrial mechanical stimulation, and provided a reliable method to treat such infertile couples.

Effect of inter-cycle interval on oocyte production in humans in the presence of the weak androgen DHEA and follicle stimulating hormone: a case-control study.

BACKGROUND: In various animal models androgens have been demonstrated to enhance follicle stimulating hormone (FSH) activity on granulosa cells during small growing follicle stages. To assess whether similar synergism may also exist in humans we investigated women on androgen (dehydroepiandrosterone, DHEA) supplementation with varying concomitant FSH exposure. METHODS: In a case controlled cohort study we determine if time interval between IVF cycles of IVF treatment with FSH had an effect on ovarian response to ovulation induction in women supplemented with DHEA. Among 85 women with known low functional ovarian reserve (LFOR), supplemented with DHEA, and undergoing at least 3 consecutive IVF cycles, 68 demonstrated short (<120 days) intervals between repeated cycles (Group 1) and were, therefore, considered to have consistent FSH exposure. In contrast 17 women (Group 2) demonstrated long (>=120 days) intervals between repeated cycles and, therefore, were considered to demonstrate inconsistent FSH exposure. Trends in oocyte yields were compared between these groups, utilizing mixed model repeated measures ANOVA, adjusted for initial age and FSH dose. RESULTS: Only women in Group I demonstrated a linear increase in oocyte yields across their three cycles of treatments (F=7.92; df 1, 68.6; p=0.017). Moreover, the analysis revealed a significant interaction between the two patient groups and cycle number for retrieved oocytes (F=6.32, df=2, 85.9, p=0.003). CONCLUSIONS: This study offers preliminary confirmatory evidence that repeated short interval exposure to androgens in combination with FSH improves human FOR. A higher level of evidence will require prospectively randomized studies.

Office diagnostic and operative hysteroscopy using local anesthesia only: an analysis of patient reported pain and other procedural outcomes.

STUDY OBJECTIVE: To evaluate the effectiveness of a multimodality local anesthetic protocol for office diagnostic and operative hysteroscopy. DESIGN: Retrospective cohort study (Canadian Task Force classification II-3). SETTING: Academic community-based institution. PATIENTS: Five hundred sixty-nine women undergoing 639 office-based diagnostic or operative hysteroscopic procedures. INTERVENTIONS: Multimodality local anesthetic protocol addressing vagina, cervix, paracervical region, and endometrial cavity. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were numeric pain scores and rate of premature termination because of pain. Secondary outcomes included procedure pain and parity, delivery route, menopausal status, procedure type, and cost effect on procedure delivery. The overall mean (SD) pain score across 535 evaluable procedures was 3.7 (2.5). Patients undergoing operative hysteroscopy had a higher mean maximum pain score than did those who underwent diagnostic hysteroscopy only (4.1 vs 3.2; p < .001). There was no difference among women in different age groups; however, those with both cesarean section and vaginal delivery had scores higher than the mean (4.7 [0.4]; p < .001). The estimated cost savings was almost $2 million. CONCLUSION: Using a multimodality approach to local anesthesia, a broad spectrum of diagnostic and operative procedures can be performed successfully, comfortably, and inexpensively in the context of an office procedure room, without the need for procedural sedation.

Is there a role for DHEA supplementation in women with diminished ovarian reserve?

PURPOSE: Poor ovarian reserve and poor ovarian response presents a challenge to IVF centers. Dehydroepiandrosterone (DHEA) supplementation is increasingly being used by many IVF centers around the world in poor responders despite the lack of convincing data. We therefore examined the rationale for the use of DHEA in poor responders, address the relevant studies, present new data, and address its potential mechanisms of action. METHODS: All published articles on the role of DHEA in infertile women from 1990 to April 2013 were reviewed. RESULTS: Several studies have suggested an improvement in pregnancy rates with the use of DHEA. Potential mechanisms include improved follicular steroidogenesis, increased IGF-1, acting as a pre-hormone for follicular testosterone, reducing aneuploidy, and increasing AMH and antral follicle count. While the role of DHEA is intriguing, evidence-based recommendations are lacking. CONCLUSIONS: While nearly 25 % of IVF programs use DHEA currently, large randomized prospective trials are sorely needed. Until (and if) such trials are conducted, DHEA may be of benefit in suitable, well informed, and consented women with diminished ovarian reserve.

Combined manual therapy techniques for the treatment of women with infertility: a case series.

Current management options for infertility, including hormone therapy, intrauterine insemination, and in vitro fertilization, tend to be expensive, are not necessarily covered by insurance, and carry different levels of short-term and long-term health risks. Many of the issues that contribute to infertility can be traced to scar tissue, fascial restriction, and lymphatic congestion in the pelvic region. Manual therapy techniques exist to release fascial restrictions, to mobilize tight ligaments, and to drain congested lymphatics, all of which can be applied to the reproductive system. In this case series, 10 infertile women were treated with 1 to 6 sessions of manual therapy applied to the pelvic region. Techniques included muscle energy, lymphatic drainage, and visceral manipulation. Six of the 10 women conceived within 3 months of the last treatment session, and all 6 of those women delivered at full term.

Dehydroepiandrosterone supplementation increases baseline follicular phase progesterone levels.

The use of dehydroepiandrosterone (DHEA) supplementation in infertile patients with diminished ovarian reserve (DOR) has become increasingly popular. It has been our observation that serum progesterone levels during the follicular phase are often increased during controlled ovarian stimulation when DHEA is coadministered. Our aim was to compare progesterone levels during the follicular phase before and during DHEA supplementation in women with DOR undergoing in vitro fertilization (IVF). In a case-control study, we compared progesterone levels during the follicular phase in IVF cycles before and during DHEA supplementation in 15 women with DOR who received 75 mg of DHEA daily. Progesterone levels on stimulation day 5 (0.5 ± 0.29 ng/ml vs. 1.54 ± 0.49 ng/ml; p < 0.0001) and on the day of human chorionic gonadotropin administration (0.75 ± 0.31 ng/ml vs. 1.87 ± 0.49 ng/ml; p < 0.0001) were significantly higher during DHEA treatment. The number of retrieved and fertilized oocytes was similar in both the groups. DHEA administration during IVF cycles in women with DOR causes a significant elevation of progesterone levels without an apparent deleterious effect on cycle outcome.

Miscarriage rates after dehydroepiandrosterone (DHEA) supplementation in women with diminished ovarian reserve: a case control study.

BACKGROUND: Dehydroepinadrosterone (DHEA) supplementation improves pregnancy chances in women with diminished ovarian reserve (DOR), by possibly reducing aneuploidy. Since a large majority of spontaneous miscarriages are associated with aneuploidy, one can speculate that DHEA supplementation may also reduce miscarriage rates. METHODS: We retroactively compared, utilizing two independent statistical models, miscarriage rates in 73 DHEA supplemented pregnancies at two independent North American infertility centers, age-stratified, to miscarriages reported in a national U.S. in vitro fertilization (IVF) data base. RESULTS: After DHEA supplementation the miscarriage rate at both centers was 15.1% (15.0% and 15.2%, respectively). For DHEA supplementation Mantel-Hänszel common odds ratio (and 95% confidence interval), stratified by age, was significantly lower, relative to odds of miscarriage in the general IVF control population [0.49 (0.25-0.94; p = 0.04)]. Miscarriage rates after DHEA were significantly lower at all ages but most pronounced above age 35 years. DISCUSSION: Since DOR patients in the literature are reported to experience significantly higher miscarriage rates than average IVF patients, the here observed reduction in miscarriages after DHEA supplementation exceeds, however, all expectations. Miscarriage rates after DHEA not only were lower than in an average national IVF population but were comparable to rates reported in normally fertile populations. Low miscarriage rates, comparable to those of normal fertile women, are statistically impossible to achieve in DOR patients without assumption of a DHEA effect on embryo ploidy. Beyond further investigations in infertile populations, these data, therefore, also suggest the investigations of pre-conception DHEA supplementation in normal fertile populations above age 35 years.

Treating primary infertility due to pituitary atrophy with Chinese herbs: a case report.

In the report a patient who suffered from secondary amenorrhea for 6 years and primary infertility for 2 years due to pituitary atrophy was successfully cured with Chinese herbs. After orally administered Chinese herbs for 1 month, the patient menstruated once and became pregnant later.