Observation on efficacy and underlying mechanism of cheek acupuncture on ovulation induction for infertile women with PCOS: Case series.

RATIONALE: Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder among women of childbearing age and is the primary cause of anovulatory infertility, accounting for 70% to 80% of cases. Ovulation induction is the main treatment approach for infertile patients with PCOS. Commonly utilized medications for this purpose are clomiphene citrate (CC) and letrozole (LE). Clomiphene citrate administration results in an ovulation rate ranging from 60% to 85%, while the pregnancy rate is limited to 35% to 40%, and a further reduction is observed in live birth rates. Letrozole demonstrates a slightly higher pregnancy rate and live birth rate compared to clomiphene citrate, although challenges persist in terms of longer stimulation cycles, multiple pregnancies, and the risk of ovarian hyperstimulation syndrome (OHSS). Clinical reports indicate that acupuncture therapy shows promising efficacy in treating patients with PCOS-related infertility, despite a partially unclear understanding of its underlying mechanisms. PATIENT CONCERNS: In this study, one patient did not achieve pregnancy despite more than a year of ovulation induction using clomiphene citrate and letrozole. However, after 3 months of receiving cheek acupuncture therapy, she successfully conceived and gave birth to a liveborn baby. Another patient achieved natural conception and live birth after 2 months of exclusive cheek acupuncture therapy. DIAGNOSIS: PCOS. INTERVENTIONS: Cheek acupuncture therapy. OUTCOMES: Both of them successfully conceived and gave birth to a liveborn baby. LESSONS: These findings suggest that cheek acupuncture therapy can effectively stimulate follicle development and ovulation, potentially improving endometrial receptivity. According to holographic theory, there is a biologically holographic model within the cheek region that shares a homology with the human body structure. This model provides an explanation for the regulatory effects of cheek acupuncture point stimulation on the Hypothalamic-Pituitary-Ovarian axis (HPO), which subsequently influences follicle development and ovulation in patients. Consequently, when cheek acupuncture therapy is applied alone or in combination with ovulation induction medication, patients have the ability to achieve successful pregnancy and experience a smooth delivery.

Ovulation induction with letrozole and dexamethasone in infertile patients with letrozole-resistant polycystic ovary syndrome.

PURPOSE: To assess efficacy of adjuvant dexamethasone during letrozole cycles for ovulation induction (OI) in women with letrozole-resistant polycystic ovary syndrome (PCOS). METHODS: We retrospectively evaluated 42 cycles of OI from 28 infertile women with letrozole-resistant PCOS between September 2019 and November 2022. Letrozole was initiated on cycle day 3 for 5 days and increased via a stair-step approach to 7.5 mg as indicated. Patients were deemed letrozole-resistant if no dominant follicle was identified on transvaginal ultrasound following this dose. Resistant patients then received 5 additional days of letrozole 7.5 mg with low-dose dexamethasone 0.5 mg for 7 days and had a repeat ultrasound. The primary outcome was ovulation rate determined by the presence of a dominant follicle on ultrasound. Secondary outcomes included endometrial thickness, number of measurable follicles, and pregnancy outcomes among responders. RESULTS: Twenty-two of 28 (79%) letrozole-resistant PCOS patients had evidence of ovulation after the addition of dexamethasone in 35 out of 42 (83%) cycles. Clinical pregnancy occurred in 20% of ovulatory cycles with a cumulative rate of 32%. All clinical pregnancies resulted in a live birth. Patients who responded to adjuvant dexamethasone were more likely to have a shorter duration of infertility; however, there were no differences in other demographics, serum androgens including DHEA-S, or pretreatment glycemic status. CONCLUSION: Adding dexamethasone to letrozole increased ovulation rates in letrozole-resistant PCOS patients undergoing OI with similar pregnancy outcomes to prior studies. The addition of dexamethasone is an effective, inexpensive, and safe option for PCOS patients otherwise at risk for cycle cancelation.

Clinical efficacy of Wenjing decoction in the treatment of ovulatory disorder infertility: A systematic review and meta-analysis.

OBJECTIVES: Wenjing decoction (WJD) was widely used in the treatment for ovulatory disorder infertility (ODI) in China, while its efficacy was not clearly known. In this study, we evaluated the clinical efficacy of WJD by meta-analysis. METHODS: Eight electronic databases including Cochrane Library, PubMed, Embase, Web of Science, China National Knowledge Infrastructure, WanFang Data, VIP Database, and China Biology Medicine were searched for randomized controlled trials (RCTs) published from the inception of each database to July 1, 2021, of which the interventions involve WJD and clomiphene. Outcomes included clinical efficacy rate, pregnancy rate, ovulation rate, dominant follicle diameter, endometrial thickness, estradiol, follicle-stimulating hormone, and luteinizing hormone. Meta-analysis and risk of bias were performed by RevMan 5.3 software. RESULTS: Eleven RCTs including 915 patients, of which 476 in the intervention group and 439 in the control group. Meta-analysis showed that WJD was better than clomiphene for patients with ODI in terms of clinical effective rate (odds ratio [OR] = 1.22, 95% confidence interval [CI]: 1.08-1.34), pregnancy rate (OR = 1.54, 95% CI: 1.15-2.07), ovulation rate (OR = 1.34, 95% CI: 1.07-1.67), endometrial thickness (mean difference [MD] = 1.50, 95% CI: 0.90-2.10), and dominant follicle diameter (MD = 1.85, 95% CI: 0.68-3.02). The estradiol level (MD = 91.0, 95% CI: 80.3-101.88) in patients taking WJD was significantly higher than those taking clomiphene, while the follicle-stimulating hormone level (MD = -0.93, 95% CI: -1.13 to -0.72) and the luteinizing hormone level (MD = -4.41, 95% CI: -4.80 to -4.03) in patients taking WJD was significantly lower than those taking clomiphene. Our results also indicated that WJD combined with clomiphene was better than clomiphene alone for patients with ODI in terms of pregnancy rate (OR = 1.79, 95% CI: 1.37-2.35). CONCLUSIONS: WJD may be effective in the treatment of patients with ODI. Due to the quality and quantity of literature, RCT with large sample size and high quality need to be performed to verify our conclusion.

Evaluation of an alternative heterotopic transplantation model for ovarian tissue to test pharmaceuticals improvements for fertility restoration.

BACKGROUND: Ovarian tissue cryopreservation and transplantation (OTCTP) is currently the main option available to preserve fertility in prepubertal patients undergoing aggressive cancer therapy treatments. However, a major limitation of OTCTP is follicle loss after transplantation. The mouse is a model of choice for studying ovarian function and follicle development after ovarian tissue grafting in vivo. In these mouse models, ovarian tissue or ovaries can be transplanted to different sites. Our aim was to evaluate a new alternative to heterotopic transplantation models that could be useful to test pharmaceutical improvement for ovarian grafts after OTCTP. METHODS: Slow frozen murine whole ovaries were transplanted into the mouse ears (between the external ear skin layer and the cartilage). Ovarian transplants were recovered after 3, 14 or 21 days. Grafts were analyzed by immunohistochemistry and follicle density analyses were performed. RESULTS: An increase of ovarian vascularization (CD31 and Dextran-FITC positive staining), as well as cellular proliferation (Ki67 staining) were observed 3 weeks after transplantation in comparison to 3 days. Fibrosis density, evaluated after Van Gieson staining, decreased 3 weeks after transplantation. Furthermore, transplantation of cryopreserved ovaries into ovariectomized mice favored follicle activation compared to transplantation into non-ovariectomized mice. CONCLUSION: The present study indicates that surgical tissue insertion in the highly vascularized murine ear is an effective model for ovarian grafting. This model could be helpful in research to test pharmaceutical strategies to improve the function and survival of cryopreserved and transplanted ovarian tissue.

Male vitamin D status and male factor infertility.

OBJECTIVE: To determine the association between vitamin D levels in the male partner and fertility outcomes in couples with mild male factor infertility. DESIGN: Secondary analysis of a randomized, controlled trial. SETTING: Nine fertility centers in the United States. PATIENT(S): Men (n = 154) with sperm concentration between 5 and 15 million/mL, motility ≤40%, or normal morphology ≤4% were eligible. Female partners were ovulatory, ≤40 years old, and had documented tubal patency. INTERVENTION(S): Men provided semen and blood at baseline for semen analysis and 25-hydroxyvitamin D (25(OH)D) levels. They were randomly assigned to receive a vitamin formulation including vitamin D 2,000 IU daily or placebo for up to 6 months. Couples attempted to conceive naturally during the first 3 months and with clomiphene citrate with intrauterine insemination of the female partner in months 4 through 6. MAIN OUTCOME MEASURE(S): Primary: sperm concentration, motility, morphology, and DNA fragmentation at baseline. Secondary: cumulative pregnancy, miscarriage, and live birth rates. RESULT(S): Semen parameters and sperm DNA fragmentation were not statistically significantly different between men with vitamin D deficiency and men with 25(OH)D levels ≥20 ng/mL. In addition, clinical pregnancy and live birth rates were similar. Male 25(OH)D level <20 ng/mL was associated with a higher rate of pregnancy loss (adjusted odds ratio 9.0; 95% confidence interval 1.3 to 61.3). CONCLUSION(S): Vitamin D deficiency in the male partner did not significantly impact semen parameters or treatment outcomes. Further study is warranted to better characterize the rate of miscarriage in couples with male vitamin D deficiency.

Chinese herbal medicine for subfertile women with polycystic ovarian syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is characterised by both metabolic and reproductive disorders, and affects 5% to 15% of women of reproductive age. Different western medicines have been proposed for PCOS-related subfertility, such as oral contraceptives, insulin sensitisers and laparoscopic ovarian drilling (LOD). Chinese herbal medicines (CHM) have also been used for subfertility caused by PCOS for decades, and are expected to become an alternative treatment for subfertile women with PCOS. OBJECTIVES: To assess the efficacy and safety of Chinese herbal medicine (CHM) for subfertile women with polycystic ovarian syndrome (PCOS). SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase and six other databases, from inception to 2 June 2020. In addition, we searched three trials registries, the reference lists of included trials and contacted experts in the field to locate trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing CHM versus placebo, no treatment or conventional (western) therapies for the treatment of subfertile women with PCOS. DATA COLLECTION AND ANALYSIS: Two review authors independently screened trials for inclusion, assessed the risk of bias in included studies and extracted data. We contacted primary study authors for additional information. We conducted meta-analyses. We used the odds ratios (ORs) to report dichotomous data, with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. MAIN RESULTS: We included eight RCTs with 609 participants. The comparisons in the included trials were as follows: CHM versus clomiphene, CHM plus clomiphene versus clomiphene (with or without ethinyloestradiol cyproterone acetate (EE/CPA)), CHM plus follicle aspiration plus ovulation induction versus follicle aspiration plus ovulation induction alone, and CHM plus laparoscopic ovarian drilling (LOD) versus LOD alone. The overall certainty of the evidence for most comparisons was very low. None of the included studies reported the primary outcome, live birth rate. Most studies reported the secondary outcomes, and only one study reported data on adverse events. In trials that compared CHM to clomiphene (with or without LOD in both study arms), we are uncertain of the effect of CHM on pregnancy rates (odds ratio (OR) 1.41, 95% confidence interval (CI) 0.63 to 3.19; I2 = 28%; 3 studies, 140 participants; very low certainty evidence). Results suggest that if the chance of pregnancy following clomiphene is assumed to be 21.5%, the chance following CHM would vary between 14.7% and 46.7%. No study reported data on adverse events. When CHM plus clomiphene was compared to clomiphene (with or without EE/CPA), there was low certainty evidence of a higher pregnancy rate in the CHM plus clomiphene group (OR 3.06, 95% CI 2.05 to 4.55; I2 = 10%; 6 studies, 470 participants; low certainty evidence). Results suggest that if the chance of pregnancy following clomiphene is assumed to be 31.5%, the chance following CHM plus clomiphene would vary between 48.5% and 67.7%. No data were reported on adverse events. In trials that compared CHM plus follicle aspiration and ovulation induction to follicle aspiration and ovulation induction alone, we are uncertain of the effect of CHM on pregnancy rates (OR 1.62, 95% CI 0.46 to 5.68; 1 study, 44 women; very low certainty evidence). Results suggest that if the chance of pregnancy following follicle aspiration and ovulation induction is assumed to be 29.2%, the chance following CHM with follicle aspiration and ovulation induction would vary between 15.9% and 70%. Reported adverse events included severe luteinised unruptured follicle syndrome (LUFS) (Peto OR 0.60, 95% CI 0.06 to 6.14; 1 study, 44 women; very low certainty evidence), ovarian hyperstimulation syndrome (OHSS) (Peto OR 0.16, 95% CI 0.00 to 8.19; 1 study, 44 women; very low certainty evidence) or multiple pregnancy (Peto OR 0.60, 95% CI 0.06 to 6.14; 1 study, 44 women; very low certainty evidence). These results suggest that if the chances of LUFS, OHSS, and multiple pregnancy following follicle aspiration and ovulation induction are assumed to be 8.3%, 4.2%, and 8.3% respectively, the chances following CHM with follicle aspiration and ovulation induction would be 0.5% to 35.8%, 0% to 26.3% and 0.5% to 35.8% respectively.  In trials that compared CHM plus LOD to LOD alone, we are uncertain if CHM improves pregnancy rates (OR 3.50, 95% CI 0.72 to 17.09; 1 study, 30 women; very low certainty evidence). Results suggest that if the chance of pregnancy following LOD is assumed to be 40%, the chance following CHM with LOD would vary between 32.4% and 91.9%. No data were reported on adverse events. We are uncertain of the results in the comparison groups for all outcomes. The certainty of the evidence for all other comparisons and outcomes was very low. The main limitations in the evidence were failure to report live birth or adverse events, failure to describe study methods in adequate detail and imprecision due to very low event rates and wide CIs. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the use of CHM for subfertile women with PCOS. No data are available on live birth. We are uncertain of the effect of CHM on pregnancy rates for there is no consistent evidence to indicate that CHM influences fertility outcomes. However, we find that the addition of CHM to clomiphene may improve pregnancy rates, but there is very limited, low certainty evidence for this outcome. Furthermore, there is insufficient evidence on adverse effects to indicate whether CHM is safe. In the future, well-designed, carefully conducted RCTs are needed, with a particular focus on the live birth rate and other safety indexes.

Efficacy of clomifene citrate combined Bushen Culuan Decoction for the treatment of infertility caused by polycystic ovary syndrome: A protocol of systematic review.

BACKGROUND: The aim of this study is to assess the efficacy and safety of clomifene citrate combined Bushen Culuan Decoction (CCBCD) in treating infertility caused by polycystic ovary syndrome (PCOS). METHODS: We will carry out this study to identify eligible randomized controlled trials (RCTs) in Cochrane Library, PUBMED, EMBASE, Web of Science, CINAHL, and China National Knowledge Infrastructure from inception to the present. There are no limitations to the language and publication time. We will perform study selection, data extraction, and study quality assessment. If possible, a meta-analysis will be developed to judge the comparative efficacy and safety of CCBCD with other treatments. RESULTS: The results of this study will summarize current high quality RCTs to provide direct evidence of CCBCD in treating infertility in patients with PCOS. CONCLUSION: This study may provide evidence to determine whether CCBCD is effective and safe or not for the treatment of infertility caused by PCOS. STUDY REGISTRATION: INPLASY202050090.

The efficacy of vitamin D combined with clomiphene citrate in ovulation induction in overweight women with polycystic ovary syndrome: a double blind, randomized clinical trial.

PURPOSE: The aim of this study was to assess the effect of vitamin D supplementation on ovulation rate in overweight subfertile women with PCOS undergoing ovulation induction. METHODS: This was a single center, parallel-groups, double-blind, and placebo-controlled randomized trial involving 186 eligible women undergoing induction of ovulation with clomiphene citrate (Clomid®, Aventis) 50 mg tablet twice daily starting from the third day of menstrual cycle and for 5 days combined with either oral Vitamin D (ossofortin®, EVA PHARMA) 10,000 IU twice weekly and calcium (calciprex®, Marcyrl Pharmaceutical Industries) 1250 mg twice daily or to receive a placebo with calcium for three successive induction cycles. The vitamin D or placebo supplementation started 1 month before induction cycles (total four cycles). Cycles were monitored with ultrasound follicle tracking and mid-luteal serum progesterone measurement. The primary outcome was the ovulation rate after three induction cycles. RESULTS: The study was performed during the period between January 2018 and September 2018, Eighty six (92.5%) women in the treatment group and 73 (78.5%) in the control group had successful ovulation (p = 0.007). The absolute and relative risk reduction was 14% and 65% respectively. Biochemical and clinical pregnancy occurred in 61.3 and 50.5% in the treatment group, and in 49.5 and 39.8% in the control group (p = 0.105 and 0.141 respectively). CONCLUSION: In subfertile women with PCOS undergoing induction of ovulation, vitamin D supplementation significantly improved the ovulation rate; however, there was no effect on clinical or biochemical pregnancy.

Effect of a short-term vitamin E supplementation on oxidative stress in infertile PCOS women under ovulation induction: a retrospective cohort study.

BACKGROUND: Vitamin E, which is critically important in the whole process of reproduction, can antagonize the oxidative stress caused by the oxygen free radicals and antioxidant imbalance and regulate normal physiological function of the reproductive system. The effect of short-term supplementation of vitamin E on outcomes of infertile women with polycystic ovary syndrome (PCOS) when they underwent ovulation induction with clomiphene citrate (CC) and human menopausal gonadotropin (HMG) remains unknown. METHODS: This was a retrospective cohort clinical trial from October 2015 to April 2017. A total of 321 PCOS cases underwent ovulation induction with CC and HMG. Patients in group A (n = 110) did not receive vitamin E while patients in group B (n = 105) and group C (n = 106) received oral treatment of vitamin E at 100 mg/day during follicular phase and luteal phase, respectively. RESULTS: It was observed no significant differences of ovulation rate, clinical pregnancy rate, and ongoing pregnancy rate among the three groups. It was interesting that dosage of HMG were significant lower in group B compared with those in group A and group C (P<0.05). CONCLUSIONS: A short-term supplementation of vitamin E can improve oxidative stress, and reduce exogenous HMG dosage to lower the economic cost with a similar pregnancy rate in the ovulation induction cycle. However, the supplementation does not alter the pregnancy rate in the ovulation induction cycle. TRIAL REGISTRATION: ChiCTR-OOC-14005389, 2014.

Acupuncture and clomiphene citrate for anovulatory infertility: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the comparative effectiveness of acupuncture or acupuncture combined with clomiphene citrate (CC) versus CC alone on the outcomes of anovulatory infertility. METHODS: A literature search in eight databases yielded nine randomised controlled trials (RCTs) that evaluated the comparative effectiveness of acupuncture and CC in anovulatory infertility. Subsequently, data were extracted and the studies were assessed for the quality of their methodological designs and risk of bias. Meta-analyses of the RCT data were conducted. RESULTS: Nine trials including 1441 women were included in the meta-analysis. There were no significant differences in the rates of pregnancy (odds ratio (OR) 1.18, 95% CI 0.83 to 1.69), ovulation (OR 2.57, 95% CI 0.59 to 11.29) or pregnancy loss (OR 0.98, 95% CI 0.59 to 1.63) when acupuncture was used as an adjuvant therapy alongside CC. Although acupuncture alone did not increase the ovulation rate (OR 0.41, 95% CI 0.11 to 1.49), our review demonstrated superior effects in patients who received acupuncture as a separate treatment modality with respect to both the pregnancy rate (OR 2.34, 95% CI 1.76 to 3.10) and the maximum follicular diameter (mean difference 0.50 mm, 95% CI 0.44 to 0.56 mm) when compared with CC alone. Statistical analysis also showed a reduction in the rate of pregnancy loss when acupuncture was used as a separate treatment compared with CC alone (OR 0.19, 95% CI 0.08 to 0.45). CONCLUSIONS: Based on the above pooled results of the studies, the use of acupuncture as a monotherapy significantly improved the rate of pregnancy among the study participants compared with the use of CC alone. However, any results drawn from these studies should be interpreted with caution when considering the context of clinical practice.

Effects of hyperhomocysteinaemia and metabolic syndrome on reproduction in women with polycystic ovary syndrome: a secondary analysis.

RESEARCH QUESTION: What is the association between hyperhomocysteinaemia (HHCY), metabolic syndrome, and reproductive outcomes among women with polycystic ovary syndrome (PCOS). DESIGN: A secondary analysis of PCOSAct with 21 sites in China. A total of 1000 women with PCOS were enrolled; 936 women with baseline homocysteine (HCY) were analysed. RESULTS: Higher HCY was associated with higher body mass index, free testosterone and lower FSH, fasting glucose (P < 0.001; P < 0.001; P = 0.005; P < 0.001) and ovulation rate among all participants (OR 0.59, 95% CI 0.41 to 0.86; OR 0.57, 95% CI 0.39 to 0.83 tertiles 2 and 3 versus tertile 1, respectively). The HHCY group had lower oestradiol and higher free testosterone (P = 0.04; P < 0.001) than the controls. In the metabolic syndrome group, LH, LH-FSH ratio and sex hormone-binding globulin were lowest in the metabolic syndrome group (all P < 0.001). In the HHCY group, ovulation rate decreased and the second or third trimester pregnancy loss rate increased compared with controls (OR 1.678, 95% CI 1.04 to 2.70; OR 0.03, 95% CI 0.00 to 0.42) with treatment adjustment. Compared with the controls, ovulation, conception, pregnancy, second or third trimester pregnancy loss and live birth rates were statistically lower in the metabolic syndrome group after adjusting treatment (OR 1.76, 95% CI 1.15 to 2.70; OR 1.75, 95% CI 1.15 to 2.65; OR 2.09, 95% CI 1.27 to 3.44; OR 0.02, 95% CI 0.00 to 0.33; OR 2.42 95% CI 1.42 to 4.10), and pregnancy, pregnancy loss and live birth rates remained significantly different after adjusting for treatment and sex-hormone factors (OR 1.77, 95% CI 1.05 to 2.99; OR 0.14, 95% CI 0.02 to 0.82; OR 2.02, 95% CI 1.16 to 3.50). CONCLUSIONS: In women with PCOS, HHCY contributes to increased pregnancy loss and reduced ovulation, and metabolic syndrome was related to defects in ovulation, conception, pregnancy, pregnancy loss and live birth, indicating that the two conditions lead to defects at various reproductive stages.

Action mechanisms of n-3 polyunsaturated fatty acids on the oocyte maturation and developmental competence: Potential advantages and disadvantages.

Infertility is a growing problem worldwide. Currently, in vitro fertilization (IVF) is widely performed to treat infertility. However, a high percentage of IVF cycles fails, due to the poor developmental potential of the retrieved oocyte to generate viable embryos. Fatty acid content of the follicular microenvironment can affect oocyte maturation and the subsequent developmental competence. Saturated and monounsaturated fatty acids are mainly used by follicle components as primary energy sources whereas polyunsaturated fatty acids (PUFAs) play a wide range of roles. A large body of evidence supports the beneficial effects of n-3 PUFAs in prevention, treatment, and amelioration of some pathophysiological conditions including heart diseases, cancer, diabetes, and psychological disorders. Nevertheless, current findings regarding the effects of n-3 PUFAs on reproductive outcomes in general and on oocyte quality more specifically are inconsistent. This review attempts to provide a comprehensive overview of potential molecular mechanisms by which n-3 PUFAs affect oocyte maturation and developmental competence, particularly in the setting of IVF and thereby aims to elucidate the reasons behind current discrepancies around this topic.

Inositol for subfertile women with polycystic ovary syndrome.

BACKGROUND: Subfertile women are highly motivated to try different adjunctive therapies to have a baby, and the widespread perception is that dietary supplements such as myo-inositol (MI) and D-chiro-insoitol (DCI) are associated with only benefit, and not with harm. Many fertility clinicians currently prescribe MI for subfertile women with polycystic ovary syndrome (PCOS) as pre-treatment to in vitro fertilisation (IVF) or for ovulation induction; however no high-quality evidence is available to support this practice. This review assessed the evidence for the effectiveness of inositol in subfertile women with a diagnosis of PCOS. OBJECTIVES: To evaluate the effectiveness and safety of oral supplementation of inositol for reproductive outcomes among subfertile women with PCOS who are trying to conceive. SEARCH METHODS: We searched the following databases (to July 2018): Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and AMED. We also checked reference lists and searched the clinical trials registries. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared any type, dose, or combination of oral inositol versus placebo, no treatment/standard treatment, or treatment with another antioxidant, or with a fertility agent, or with another type of inositol, among subfertile women with PCOS. DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible studies, extracted data, and assessed risk of bias. The primary outcomes were live birth and adverse effects; secondary outcomes included clinical pregnancy rates and ovulation rates. We pooled studies using a fixed-effect model, and we calculated odds ratios (ORs) with 95% confidence intervals (CIs). We assessed the overall quality of the evidence by applying GRADE criteria. MAIN RESULTS: We included 13 trials involving 1472 subfertile women with PCOS who were receiving myo-inositol as pre-treatment to IVF (11 trials), or during ovulation induction (two trials). These studies compared MI versus placebo, no treatment/standard, melatonin, metformin, clomiphene citrate, or DCI. The evidence was of 'low' to 'very low' quality. The main limitations were serious risk of bias due to poor reporting of methods, inconsistency, and lack of reporting of clinically relevant outcomes such as live birth and adverse events.We are uncertain whether MI improves live birth rates when compared to standard treatment among women undergoing IVF (OR 2.42, 95% CI 0.75 to 7.83; P = 0.14; 2 RCTs; 84 women; I² = 0%). Very low-quality evidence suggests that for subfertile women with PCOS undergoing pre-treatment to IVF who have an expected live birth rate of 12%, the rate among women using MI would be between 9% and 51%.We are uncertain whether MI may be associated with a decrease in miscarriage rate when compared to standard treatment (OR 0.40, 95% CI 0.19 to 0.86; P = 0.02; 4 RCTs; 535 women; I² = 66%; very low-quality evidence). This suggests that among subfertile women with PCOS with an expected miscarriage rate of 9% who are undergoing pre-treatment to IVF, the rate among women using MI would be between 2% and 8%; however this meta-analysis is based primarily on one study, which reported an unusually high miscarriage rate in the control group, and this has resulted in very high heterogeneity. When we removed this trial from the sensitivity analysis, we no longer saw the effect, and we noted no conclusive differences between MI and standard treatment.Low-quality evidence suggests that MI may be associated with little or no difference in multiple pregnancy rates when compared with standard treatment (OR 1.04, 95% CI 0.63 to 1.71; P = 0.89; 2 RCTs; 425 women). This suggests that among subfertile women with PCOS who are undergoing pre-treatment to IVF, with an expected multiple pregnancy rate of 18%, the rate among women using inositol would be between 12% and 27%.We are uncertain whether MI may be associated with an increased clinical pregnancy rate when compared to standard treatment (OR 1.27, 95% CI 0.87 to 1.85; P = 0.22; 4 RCTs; 535 women; I² = 0%; very low-quality evidence). This suggests that among subfertile women with PCOS who are undergoing pre-treatment to IVF, with an expected clinical pregnancy rate of 26%, the rate among women using MI would be between 24% and 40%. Ovulation rates were not reported for this comparison.Other comparisons included only one trial in each, so for the comparisons MI versus antioxidant, MI versus an insulin-sensitising agent, MI versus an ovulation induction agent, and MI versus another DCI, meta-analysis was not possible.No pooled evidence was available for women with PCOS undergoing ovulation induction, as only single trials performed comparison of the insulin-sensitising agent and the ovulation induction agent. AUTHORS' CONCLUSIONS: In light of available evidence of very low quality, we are uncertain whether MI improves live birth rate or clinical pregnancy rate in subfertile women with PCOS undergoing IVF pre-treatment taking MI compared to standard treatment. We are also uncertain whether MI decreases miscarriage rates or multiple pregnancy rates for these same women taking MI compared to standard treatment. No pooled evidence is available for use of MI versus placebo, another antioxidant, insulin-sensitising agents, ovulation induction agents, or another type of inositol for women with PCOS undergoing pre-treatment to IVF. No pooled evidence is available for use of MI in women undergoing ovulation induction.

Ovulation induction in polycystic ovary syndrome.

The objective of this narrative review was to suggest a rational order of treatment choices in anovulatory women with polycystic ovary syndrome (PCOS), for whom a multitude of treatment options exist. In obese/overweight women with PCOS the importance of weight reduction should be stressed. Inositol, a dietary supplement with a documented effect on ovulation and without adverse effects in the doses recommended, may be suggested. Additional first-line medical alternatives include insulin sensitizers, selective estrogen receptor modulators, and aromatase inhibitors. Of these, the aromatase inhibitor letrozole and the combination of clomiphene citrate and metformin have the highest rates of ovulation and live birth. Second-line treatments are ovarian electrocautery and low-dose follicle-stimulating hormone stimulation. Controlled ovarian stimulation with in vitro fertilization, should be considered the last option as it carries a significant risk of ovarian hyperstimulation syndrome in patients with PCOS.

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.

[Herb-partitioned moxibustion on navel for anovulatory infertility:a randomized controlled trial].

OBJECTIVE: To observe the efficacy differences between herb-partitioned moxibustion on navel and clomiphene for anovulatory infertility. METHODS: With double-blind double-dummy randomized control method, a total of 40 patients with anovulatory infertility were randomly divided into a moxibustion group and a clomiphene group, 20 cases in each one. Blinding was conducted on both patients and doctors. The patients in the moxibustion group were treated with herb-partitioned moxibustion on navel and oral administration of clomiphene placebo, while the patients in the clomiphene group were treated with placebo-partitioned moxibustion on navel and oral administration of clomiphene. The herb-partitioned moxibustion and placebo-partitioned moxibustion were given at the end of menstruation, 1.5 hours per treatment, once a week, and no treatment was given during menstruation. The oral administration of clomiphene and clomiphene placebo were given from 5 days into menstruation, 50 mg, once a day, for consecutive 5 days. One menstrual cycle was taken as one treatment course, and 3 treatment courses were conducted. After 3 treatment courses, the endometrial thickness (ET), maximum follicular diameter (MFD), ovulation rate (OR) and effective rate (ER) were evaluated between the two groups. RESULTS: (1) Compared before treatment, ET was significantly increased after treatment in the two groups (both P<0.05); after treatment, the ET in the moxibustion group was higher than that in the clomiphene group (P<0.05). (2) After treatment, MFD was significantly increased in the moxibustion group (P<0.05) and insignificantly increased in the clomiphene group (P>0.05); the MFD in the moxibustion group was higher than that in the clomiphene group (P<0.05). (3) The OR was 75.0% (15/20) and 65.0% (13/20) in the two groups respectively, which were not significantly different (P>0.05). (4) The total ER in the moxibustion group was 95.0% (19/20), which was superior to 70.0% (14/20) in the clomiphene group (P<0.05). CONCLUSIONS: The clinical efficacy of herb-partitioned moxibustion at navel on anovulatory infertility was superior to that of clomiphene, but their effects on OR was similar.

Ovarian Stimulation in Poor Responders: Have We Made Progress?

BACKGROUND: Poor ovarian responders (POR) pose a challenge to a physicians' ability to choose a stimulation protocol that maximizes the number of oocytes harvested and their chances of conception with multiple protocols aimed at improving pregnancy rates in this poor prognosis population. The Bologna criteria standardized the diagnosis of POR and allows for a more homogenous patient population in clinical trials. METHODS: A structured review of the literature, which encompasses research on Bologna-defined POR, identified several proposed protocols to optimize pregnancy rates in poor responders. In addition, we reviewed the utility of utilizing oocyte quality enhancers such as luteal pre-treatment, coenzyme Q10 (CoQ10), dihydroepiandrosterone (DHEA), and growth hormone (GH). CONCLUSION: Controlled ovarian stimulation strategies with adjuvant aromatase inhibitors and clomiphene citrate have shown similar pregnancy outcomes to higher dose gonadotropin in GnRH antagonist protocols. While the standardization of Bologna defined POR has allowed for more comparable patient populations to study the effectiveness of different protocols for ovarian stimulation, there is currently no convincing data that has determined the ideal protocol for controlled ovarian stimulation in this patient population. Further research is needed to identify optimal treatment strategies.

Could myo-inositol soft gel capsules outperform clomiphene in inducing ovulation? Results of a pilot study.

OBJECTIVE: Insulin resistance is known to worsen polycystic ovarian syndrome (PCOS). The management of insulin resistance is crucial in the treatment of PCOS and insulin-sensitizing molecule as myo-inositol (MYO) seems to have promising effects. The aim of our pilot study was to study whether supplementation with MYO can improve patients' sensitivity to clomiphene citrate (CC) in terms of ovulation and pregnancy rates. PATIENTS AND METHODS: This study included 26 patients with PCOS, eligible to ovulation induction with CC. All of them received MYO in combination with CC and folic acid, following the usual protocol. Results concerning ovulation and pregnancy rates were compared to those from our historical cohort of PCOS patients treated with CC alone. RESULTS: Ovulation rate was significantly higher with MYO+CC than with CC alone (65.5% vs. 42%, p=0.0001). The number of patients sensitive to 50 mg/d was 54% with MYO vs. 40% in our reference cohort (NS). The total resistance rate was 19% vs. 27% in the reference cohort (NS). Cumulative pregnancy rate with MYO+CC was 53.8% vs. 42.2% with CC alone (NS). Pregnancy rates per initiated cycle were 16.1% with MYO vs. 12.6% in the historical cohort (NS). DISCUSSION: Although the differences were not significant for most outcomes, probably due to the small number of patients, our pilot study seemed to show a benefit of supplementation with MYO during ovulation induction with CC in PCOS patients. CONCLUSIONS: This study proves the great interest of a RCT and re-opens the possibilities of insulin-sensitizing agents in the treatment of anovulatory patients with PCOS, such as natural products like MYO.