Acupuncture is used to induce ovulation in some women with polycystic ovary syndrome, without supporting clinical evidence.
To assess whether active acupuncture, either alone or combined with ...clomiphene, increases the likelihood of live births among women with polycystic ovary syndrome.
A double-blind (clomiphene vs placebo), single-blind (active vs control acupuncture) factorial trial was conducted at 21 sites (27 hospitals) in mainland China between July 6, 2012, and November 18, 2014, with 10 months of pregnancy follow-up until October 7, 2015. Chinese women with polycystic ovary syndrome were randomized in a 1:1:1:1 ratio to 4 groups.
Active or control acupuncture administered twice a week for 30 minutes per treatment and clomiphene or placebo administered for 5 days per cycle, for up to 4 cycles. The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation; the control acupuncture group received superficial needle insertion, no manual stimulation, and mock electricity.
The primary outcome was live birth. Secondary outcomes included adverse events.
Among the 1000 randomized women (mean SD age, 27.9 3.3 years; mean SD body mass index, 24.2 4.3), 250 were randomized to each group; a total of 926 women (92.6%) completed the trial. Live births occurred in 69 of 235 women (29.4%) in the active acupuncture plus clomiphene group, 66 of 236 (28.0%) in the control acupuncture plus clomiphene group, 31 of 223 (13.9%) in the active acupuncture plus placebo group, and 39 of 232 (16.8%) in the control acupuncture plus placebo group. There was no significant interaction between active acupuncture and clomiphene (P = .39), so main effects were evaluated. The live birth rate was significantly higher in the women treated with clomiphene than with placebo (135 of 471 28.7% vs 70 of 455 15.4%, respectively; difference, 13.3%; 95% CI, 8.0% to 18.5%) and not significantly different between women treated with active vs control acupuncture (100 of 458 21.8% vs 105 of 468 22.4%, respectively; difference, -0.6%; 95% CI, -5.9% to 4.7%). Diarrhea and bruising were more common in patients receiving active acupuncture than control acupuncture (diarrhea: 25 of 500 5.0% vs 8 of 500 1.6%, respectively; difference, 3.4%; 95% CI, 1.2% to 5.6%; bruising: 37 of 500 7.4% vs 9 of 500 1.8%, respectively; difference, 5.6%; 95% CI, 3.0% to 8.2%).
Among Chinese women with polycystic ovary syndrome, the use of acupuncture with or without clomiphene, compared with control acupuncture and placebo, did not increase live births. This finding does not support acupuncture as an infertility treatment in such women.
clinicaltrials.gov Identifier: NCT01573858.
Despite 30 years of advocacy, the prevalence of non-therapeutic female genital alteration (FGA) in minors is stable in many countries. Educational efforts have minimally changed the prevalence of ...this procedure in regions where it has been widely practiced. In order to better protect female children from the serious and long-term harms of some types of non-therapeutic FGA, we must adopt a more nuanced position that acknowledges a wide spectrum of procedures that alter female genitalia. We offer a revised categorisation for non-therapeutic FGA that groups procedures by effect and not by process. Acceptance of de minimis procedures that generally do not carry long-term medical risks is culturally sensitive, does not discriminate on the basis of gender, and does not violate human rights. More morbid procedures should not be performed. However, accepting de minimis non-therapeutic f FGA procedures enhances the effort of compassionate practitioners searching for a compromise position that respects cultural differences but protects the health of their patients.
Perivascular epithelioid cell tumor (PEComa) belongs to a family of tumors characterized by coexpression of melanocytic and muscle markers. Recent studies have shown that sporadic and tuberous ...sclerosis complex-associated PEComa may respond to mTOR inhibitors underscoring the importance of recognizing this tumor. However, its occurrence in the gynecologic tract continues to be disputed owing to its common misclassification as other types of uterine sarcoma and its controversial relationship with epithelioid smooth muscle tumors. To more fully characterize PEComa of the female genital tract, 16 cases of gynecologic PEComa were identified (1990 to 2012) and formed the basis of this study. Each case was analyzed for conventional morphologic and immunohistochemical characteristics established for PEComa of extrauterine sites; clinical outcome data were obtained for all cases. The 16 patients were aged 28 to 60 (mean 49; median 50) years, and 1 had a history of tuberous sclerosis complex. Thirteen cases were primary of the uterus, 2 of the adnexa, and 1 of the vagina. Tumor size ranged from 0.3 to 25.0 (mean 8.7) cm. Three patients died of disease, 6 were alive with disease, and 7 were alive without evidence of disease at last follow-up (1 mo to 13 y follow-up; mean 26 mo). All patients with an adverse outcome met established criteria for malignancy as proposed for extrauterine sites (ie, 2 or more features present: size ≥5 cm, high-grade nuclear features, infiltration, necrosis, lymphovascular invasion, or a mitotic rate ≥1/50 high-power fields). Of the melanocytic markers, HMB45 was most commonly expressed (16/16 positive, 100%), followed by microphthalmia transcription factor (11/12 positive, 92%), MelanA (14/16 positive, 88%), and S100 protein (2/10 positive, 20%). Of the smooth muscle markers, desmin was most commonly expressed (15/15 cases, 100%), followed by SMA (14/15 cases, 93%) and h-caldesmon (11/12 cases, 92%). TFE3 immunopositivity was identified in 5 of 13 cases; however, 3 tested cases were negative for a TFE3 rearrangement by fluorescence in situ hybridization. Current criteria for malignancy appear to be valid in the female genital tract, although modified criteria, as described herein, may be more specific. Awareness of the characteristic features of PEComa is important to help distinguish it from epithelioid smooth muscle tumors and other mimics as PEComa may respond to unique chemotherapeutic regimens.
Background
Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It affects about 5% to 20% of women worldwide and ...often leads to anovulatory infertility. Aromatase inhibitors (AIs) are a class of drugs that were introduced for ovulation induction in 2001. Since about 2001 clinical trials have reached differing conclusions as to whether the AI, letrozole, is at least as effective as the first‐line treatment clomiphene citrate (CC), a selective oestrogen receptor modulator (SERM).
Objectives
To evaluate the effectiveness and safety of AIs (letrozole) (with or without adjuncts) compared to SERMs (with or without adjuncts) for infertile women with anovulatory PCOS for ovulation induction followed by timed intercourse or intrauterine insemination.
Search methods
We searched the following sources, from their inception to 4 November 2021, to identify relevant randomised controlled trials (RCTs): the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase and PsycINFO. We also checked reference lists of relevant trials, searched the trial registers and contacted experts in the field for any additional trials. We did not restrict the searches by language or publication status.
Selection criteria
We included all RCTs of AIs used alone or with other medical therapies for ovulation induction in women of reproductive age with anovulatory PCOS.
Data collection and analysis
Two review authors independently selected trials, extracted the data and assessed risks of bias using RoB 1. We pooled trials where appropriate using a fixed‐effect model to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for most outcomes, and risk differences (RDs) for ovarian hyperstimulation syndrome (OHSS). The primary outcomes were live birth rate and OHSS rate. Secondary outcomes were clinical pregnancy, miscarriage and multiple pregnancy rates. We assessed the certainty of the evidence for each comparison using GRADE methods.
Main results
This is a substantive update of a previous review; of six previously included trials, we excluded four from this update and moved two to 'awaiting classification' due to concerns about validity of trial data. We included five additional trials for this update that now includes a total of 41 RCTs (6522 women). The AI, letrozole, was used in all trials.
Letrozole compared to SERMs with or without adjuncts followed by timed intercourse
Live birth rates were higher with letrozole (with or without adjuncts) compared to SERMs followed by timed intercourse (OR 1.72, 95% CI 1.40 to 2.11; I2 = 0%; number needed to treat for an additional beneficial outcome (NNTB) = 10; 11 trials, 2060 participants; high‐certainty evidence). This suggests that in women with a 20% chance of live birth using SERMs, the live birth rate in women using letrozole with or without adjuncts would be 27% to 35%. There is high‐certainty evidence that OHSS rates are similar with letrozole or SERMs (0.5% in both arms: risk difference (RD) −0.00, 95% CI −0.01 to 0.01; I2 = 0%; 10 trials, 1848 participants; high‐certainty evidence). There is evidence for a higher pregnancy rate in favour of letrozole (OR 1.69, 95% CI 1.45 to 1.98; I2 = 0%; NNTB = 10; 23 trials, 3321 participants; high‐certainty evidence). This suggests that in women with a 24% chance of clinical pregnancy using SERMs, the clinical pregnancy rate in women using letrozole with or without adjuncts would be 32% to 39%. There is little or no difference between treatment groups in the rate of miscarriage per pregnancy (25% with SERMs versus 24% with letrozole: OR 0.94, 95% CI 0.66 to 1.32; I2 = 0%; 15 trials, 736 participants; high‐certainty evidence) and multiple pregnancy rate (2.2% with SERMs versus 1.6% with letrozole: OR 0.74, 95% CI 0.42 to 1.32; I2 = 0%; 14 trials, 2247 participants; high‐certainty evidence). However, a funnel plot showed mild asymmetry, indicating that some trials in favour of SERMs might be missing.
Letrozole compared to laparoscopic ovarian drilling (LOD)
One trial reported very low‐certainty evidence that live birth rates may be higher with letrozole compared to LOD (OR 2.07, 95% CI 0.99 to 4.32; 1 trial, 141 participants; very low‐certainty evidence). This suggests that in women with a 22% chance of live birth using LOD with or without adjuncts, the live birth rate in women using letrozole with or without adjuncts would be 24% to 47%. No trial reported OHSS rates. Due to the low‐certainty evidence we are uncertain if letrozole improves pregnancy rates compared to LOD (OR 1.47, 95% CI 0.95 to 2.28; I² = 0%; 3 trials, 367 participants; low‐certainty evidence). This suggests that in women with a 29% chance of clinical pregnancy using LOD with or without adjuncts, the clinical pregnancy rate in women using letrozole with or without adjuncts would be 28% to 45%. There seems to be no evidence of a difference in miscarriage rates per pregnancy comparing letrozole to LOD (OR 0.65, 95% CI 0.22 to 1.92; I² = 0%; 3 trials, 122 participants; low‐certainty evidence). This also applies to multiple pregnancies (OR 3.00, 95% CI 0.12 to 74.90; 1 trial, 141 participants; very low‐certainty evidence).
Authors' conclusions
Letrozole appears to improve live birth rates and pregnancy rates in infertile women with anovulatory PCOS, compared to SERMs, when used for ovulation induction, followed by intercourse. There is high‐certainty evidence that OHSS rates are similar with letrozole or SERMs. There was high‐certainty evidence of no difference in miscarriage rate and multiple pregnancy rate. We are uncertain if letrozole increases live birth rates compared to LOD. In this update, we added good quality trials and removed trials with concerns over data validity, thereby upgrading the certainty of the evidence base.
Offending Womenis an eye-opening journey into the lived reality of prison for women in the United States today. Lynne Haney looks at incarcerated mothers, housed together with their children, who are ...serving terms in alternative, community-based prisons-a type of facility that is becoming increasingly widespread. Incorporating vivid, sometimes shocking observations of daily life, she probes the dynamics of power over women's minds and bodies that play out in two such institutions in California. She finds that these "alternative" prisons, contrary to their aims, often end up disempowering women, transforming their social vulnerabilities into personal pathologies, and pushing them into a state of disentitlement. Uncovering the complex gendered underpinning of methods of control and intervention used in the criminal justice system today,Offending Womenlinks that system to broader discussions on contemporary government and state power, asks why these strategies have arisen at this particular moment in time, and considers what forms of citizenship they have given rise to.
Background:
Identifying the risk factors associated with a bone stress injury (BSI), including stress reactions and stress fractures, may aid in targeting those at increased risk and in formulating ...prevention guidelines for exercising girls and women.
Purpose:
To evaluate the effect of single or combined risk factors as defined by the female athlete triad—a syndrome involving 3 interrelated spectrums consisting of energy availability, menstrual function, and bone mass—with the incidence of BSIs in a multicenter prospective sample of 4 cohorts of physically active girls and women.
Study Design:
Cohort study; Level of evidence, 3.
Methods:
At baseline, participants’ (N = 259; mean age, 18.1 ± 0.3 years) anthropometric characteristics, eating attitudes and behaviors, menstrual function, sports participation or exercise activity, and pathological weight control behaviors were assessed. Dual-energy x-ray absorptiometry (DXA) measured the bone mass of the whole body, total hip, femoral neck, lumbar spine, and body composition. Participants were followed prospectively for the occurrence of injuries; those injuries confirmed by a physician were recorded.
Results:
Twenty-eight participants (10.8%) incurred a BSI. Forty-six percent of those who had ≥12 h/wk of purposeful exercise, a bone mineral density (BMD) Z score <–1.0, and who exhibited 3 to 4 of the following: BMI <21.0 kg/m2, oligo- or amenorrhea, elevated dietary restraint, and/or participation in a leanness sport exercise/activity at baseline, incurred a BSI during the prospective study period. Single factors significantly (P < .05) associated with the development of a BSI included ≥12 h/wk of purposeful exercise (14.7%), BMI <21.0 kg/m2 (15.3%), and low bone mass (BMD Z score <–1.0; 21.0%). The strongest 2- and 3-variable combined risk factors were low BMD (Z score <–1.0) + ≥12 h/wk of exercise, with 29.7% incurring a BSI (odds ratio OR, 5.1; 95% CI, 2.2-12.1), and ≥12 h/wk of exercise + leanness sport/activity + dietary restraint, with 46.2% incurring a BSI (OR, 8.7; 95% CI, 2.7-28.3).
Conclusion:
In the sample, which included female adolescents and young adults participating in competitive or recreational exercise activities, the risk of BSIs increased from approximately 15% to 20% for significant single risk factors to 30% to 50% for significant combined female athlete triad–related risk factor variables. These data support the notion that the cumulative risk for BSIs increases as the number of Triad-related risk factors accumulates.
Oocyte maturation arrest and early embryonic arrest are important reproductive phenotypes resulting in female infertility and cause the recurrent failure of assisted reproductive technology (ART). ...However, the genetic etiologies of these female infertility-related phenotypes are poorly understood. Previous studies have mainly focused on inherited mutations based on large pedigrees or consanguineous patients. However, the role of de novo mutations (DNMs) in these phenotypes remains to be elucidated.
To decipher the role of DNMs in ART failure and female infertility with oocyte and embryo defects, we explore the landscape of DNMs in 473 infertile parent-child trios and identify a set of 481 confident DNMs distributed in 474 genes. Gene ontology analysis reveals that the identified genes with DNMs are enriched in signaling pathways associated with female reproductive processes such as meiosis, embryonic development, and reproductive structure development. We perform functional assays on the effects of DNMs in a representative gene Tubulin Alpha 4a (TUBA4A), which shows the most significant enrichment of DNMs in the infertile parent-child trios. DNMs in TUBA4A disrupt the normal assembly of the microtubule network in HeLa cells, and microinjection of DNM TUBA4A cRNAs causes abnormalities in mouse oocyte maturation or embryo development, suggesting the pathogenic role of these DNMs in TUBA4A.
Our findings suggest novel genetic insights that DNMs contribute to female infertility with oocyte and embryo defects. This study also provides potential genetic markers and facilitates the genetic diagnosis of recurrent ART failure and female infertility.
The Division of Cancer Prevention and the Division of Cancer Biology at the National Cancer Institute and the Gynecologic Health and Disease Branch in the National Institute of Child Health and Human ...Development organized a workshop in April 2019 to explore current insights into the progression of gynecologic cancers from benign conditions. Working groups were formed based on 3 gynecologic disease types: (1) Endometriosis or Endometrial Cancer and Endometrial-Associated Ovarian Cancer, (2) Uterine Fibroids (Leiomyoma) or Leiomyosarcoma, and (3) Adenomyosis or Adenocarcinoma. In this report, we highlight the key questions and current challenges that emerged from the working group discussions and present potential research opportunities that may advance our understanding of the progression of gynecologic benign conditions to cancer.
Context:
Experimental evidence supports a relevance of vitamin D (VitD) for reproduction; however, data in humans are sparse and inconsistent.
Objective:
To assess the relationship of VitD status ...with ovulation induction (OI) outcomes in women with polycystic ovary syndrome (PCOS).
Design:
A retrospective cohort.
Setting:
Secondary analysis of randomized controlled trial data.
Participants:
Participants in the Pregnancy in PCOS I (PPCOS I) randomized controlled trial (n = 540) met the National Institutes of Health diagnostic criteria for PCOS.
Interventions:
Serum 25OHD levels were measured in stored sera.
Main Outcome Measures:
Primary, live birth (LB); secondary, ovulation and pregnancy loss after OI.
Results:
Likelihood for LB was reduced by 44% for women if the 25OHD level was < 30 ng/mL (<75 nmol/L; odds ratio OR, 0.58 0.35–0.92). Progressive improvement in the odds for LB was noted at thresholds of ≥38 ng/mL (≥95 nmol/L; OR, 1.42 1.08–1.8), ≥40 ng/mL (≥100 nmol/L; OR, 1.51 1.05–2.17), and ≥45 ng/mL (≥112.5 nmol/L; OR, 4.46 1.27–15.72). On adjusted analyses, VitD status was an independent predictor of LB and ovulation after OI.
Conclusions:
In women with PCOS, serum 25OHD was an independent predictor of measures of reproductive success after OI. Our data identify reproductive thresholds for serum 25OHD that are higher than recommended for the nonpregnant population.
Stored sera from a RCT (Pregnancy in Polycystic Ovary Syndrome I) were assayed for 25OHD; vitamin D status was identified as an independent predictor of live birth following ovulation induction in women with PCOS.
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