Inositol for Polycystic Ovary Syndrome: a systematic review and meta-analysis to inform the 2023 update of the International Evidence-Based PCOS Guidelines.

CONTEXT: Insulin resistance is common in women with Polycystic Ovary Syndrome (PCOS). Inositol may have insulin sensitising effects; however, its efficacy in the management of PCOS remains indeterminate. OBJECTIVE: To inform the 2023 International Evidence-based Guidelines in PCOS, this systematic review and meta-analysis evaluated the efficacy of inositol, alone or in combination with other therapies, in the management of PCOS. DATA SOURCES: Medline, PsycInfo, EMBASE, All EBM, and CINAHL from inception until August 2022. STUDY SELECTION: Thirty trials (n=2230; 1093 intervention, 1137 control), with 19 pooled in meta-analyses were included. DATA EXTRACTION: Data were extracted for hormonal, metabolic, lipids, psychological, anthropometric, reproductive outcomes and adverse effects by one reviewer, independently verified by a second. DATA SYNTHESIS: Thirteen comparisons were assessed, with three in meta-analyses. Evidence suggests benefits for myo-inositol or D-chiro-inositol (DCI) for some metabolic measures and potential benefits from DCI for ovulation but inositol may have no effect on other outcomes. Metformin may improve waist-hip ratio and hirsutism compared to inositol but there is likely no difference for reproductive outcomes, and the evidence is very uncertain for BMI. Myo-inositol likely causes fewer gastrointestinal adverse events compared with metformin; however, these are typically mild and self-limited. CONCLUSIONS: The evidence supporting the use of inositol in the management of PCOS is limited and inconclusive. Clinicians and their patients should consider the uncertainty of the evidence together with individual values and preferences when engaging in shared decision-making regarding the use of inositol for PCOS.

Exploring the relationship between history of infertility and the experience of menopausal symptoms.

OBJECTIVE: The aim of the study is to examine longitudinal associations of history of infertility with menopausal symptoms in midlife. METHODS: Six hundred ninety-five midlife women (≥45 y old or reporting ≥12 mo of amenorrhea at the midlife visit) in Project Viva, a prospective cohort enrolled 1999-2002 during pregnancy and followed for 18 years after enrollment ("midlife visit"). Exposure was history of infertility defined as time to pregnancy ≥12 months (≥6 mo if ≥35 y), use of medical treatment to conceive, or infertility consultation or treatment in the 6-month preceding enrollment. The primary outcome was score below or above the median on the Menopause Rating Scale (MRS). Secondary outcomes included individual symptom score on the MRS and self-reported age of menopause. RESULTS: A total of 36.6% had a history of infertility in their lifetime. At the time of MRS completion, the women with prior infertility were older (53.4 [SD, 3.8] vs 51.2 [SD, 3.7] y) than those without infertility and a larger proportion had reached menopause (62% vs 40%). Women with prior infertility were more likely to score above the median on the MRS (Adjusted Odds Ratio [aOR], 1.45; 95% confidence interval [CI], 1.04-2.01) and had higher odds for reporting any depressive mood (aOR, 1.56; 95% CI, 1.12-2.16) and irritability (aOR, 1.57; 95% CI, 1.13-2.19). There was a trend toward greater severity of sleep problems among women with prior infertility. There was no association of prior infertility with report of other menopausal symptoms or age of menopause. CONCLUSIONS: Our findings suggest that women with prior infertility are more likely to have an MRS score above the median and experience depressive mood, irritability, and sleep problems during midlife than women without infertility. These findings have implications for mental health screening among midlife women.

The impact of cryopreserved sperm on intrauterine insemination outcomes: is frozen as good as fresh?

Introduction: Frozen sperm utilization might negatively impact cycle outcomes in animals, implicating cryopreservation-induced sperm damage. However, in vitro fertilization and intrauterine insemination (IUI) in human studies are inconclusive. Methods: This study is a retrospective review of 5,335 IUI [± ovarian stimulation (OS)] cycles from a large academic fertility center. Cycles were stratified based on the utilization of frozen (FROZEN, n = 1,871) instead of fresh ejaculated sperm (FRESH, n = 3,464). Main outcomes included human chorionic gonadotropin (HCG) positivity, clinical pregnancy (CP), and spontaneous abortion (SAB) rates. Secondary outcome was live birth (LB) rate. Odds ratios (OR) for all outcomes were calculated utilizing logistic regression and adjusted (adjOR) for maternal age, day-3 FSH, and OS regimen. Stratified analysis was performed based on OS subtype [gonadotropins; oral medications (OM): clomiphene citrate and letrozole; and unstimulated/natural]. Time to pregnancy and cumulative pregnancy rates were also calculated. Further subanalyses were performed limited to either the first cycle only or to the partner's sperm only, after excluding female factor infertility, and after stratification by female age (<30, 30-35, and >35 years old). Results: Overall, HCG positivity and CP were lower in the FROZEN compared to the FRESH group (12.2% vs. 15.6%, p < 0.001; 9.4% vs. 13.0%, p < 0.001, respectively), which persisted only among OM cycles after stratification (9.9% vs. 14.2% HCG positivity, p = 0.030; 8.1% vs. 11.8% CP, p = 0.041). Among all cycles, adjOR (95% CI) for HCG positivity and CP were 0.75 (0.56-1.02) and 0.77 (0.57-1.03), respectively, ref: FRESH. In OM cycles, adjOR (95% CI) for HCG positivity [0.55 (0.30-0.99)] and CP [0.49 (0.25-0.95), ref.: FRESH] favored the FRESH group but showed no differences among gonadotropin and natural cycles. SAB odds did not differ between groups among OM and natural cycles but were lower in the FROZEN group among gonadotropin cycles [adjOR (95% CI): 0.13 (0.02-0.98), ref.: FRESH]. There were no differences in CP and SAB in the performed subanalyses (limited to first cycles or partner's sperm only, after excluding female factors, or after stratification according to female age). Nevertheless, time to conception was slightly longer in the FROZEN compared to the FRESH group (3.84 vs. 2.58 cycles, p < 0.001). No significant differences were present in LB and cumulative pregnancy results, other than in the subgroup of natural cycles, where higher LB odds [adjOR (95% CI): 1.08 (1.05-1.12)] and higher cumulative pregnancy rate (34% vs. 15%, p = 0.002) were noted in the FROZEN compared to the FRESH group. Conclusion: Overall, clinical outcomes did not differ significantly between frozen and fresh sperm IUI cycles, although specific subgroups might benefit from fresh sperm utilization.

Ovarian torsion during ovarian stimulation prior to trigger followed by successful oocyte retrieval: A case report.

Objective: To report a case of ovarian torsion during ovarian stimulation prior to trigger followed by laparoscopic detorsion, trigger, and subsequent successful oocyte retrieval, as well as to review outcomes from the cycle. Case Presentation: A 32-year-old woman with a history of recurrent ovarian torsion presented with ovarian torsion during ovarian stimulation for in vitro fertilization prior to trigger injection. She underwent laparoscopic ovarian detorsion followed by trigger and oocyte retrieval.The rate of fertilization and blastocyst conversion of oocytes retrieved from the ovary affected by torsion was lower than from the contralateral ovary. Viable oocytes and an embryo were produced by the affected ovary. Conclusion: Ovarian torsion during ovarian hyperstimulation for in vitro fertilization is a rare occurrence, particularly prior to trigger. Clinicians can consider proceeding with trigger and oocyte retrieval after treating ovarian torsion in appropriately counseled patients.

The impact of anti-Müllerian hormone on endometrial thickness in gonadotropin stimulation/intrauterine insemination cycles: is there an effect on pregnancy outcomes?

PURPOSE: To study the association, if any, between anti-Müllerian hormone (AMH) and pre-ovulatory endometrial thickness (ET) in gonadotropin/intrauterine insemination (IUI) cycles. METHODS: This retrospective cohort study included a total of 964 patients undergoing 1926 gonadotropin/IUI cycles at an academic fertility center. Primary outcome measure was the association between serum AMH and measured ET on the day of and the day before human chorionic gonadotropin hormone (hCG) ovulation trigger. The effect of a model combining AMH and ET on early pregnancy outcomes was a secondary measure. RESULTS: In 52.8% of cycles, ET was last assessed and recorded on the day of hCG administration, while in the remaining 47.2% on the day prior to trigger. In unadjusted regression models, AMH was weakly correlated with ET on hCG trigger day [bAMH (95%CI) = 0.032 (- 0.008, 0.070), p = 0.015]. When adjusting for potential confounders, the positive correlation became significant [0.051 (0.006, 0.102), p = 0.047]. Similar findings were observed when assessing the correlation between AMH and ET on the day prior to hCG trigger. ET was non-significantly associated with the odds of clinical pregnancy, when adjusting for potential confounders, except for when restricting the analysis to couples with idiopathic infertility [OR (95%CI), p-value: 0.787 (0.623, 0.993), 0.044]. CONCLUSION: Our findings support an effect of serum AMH on endometrial development in gonadotropin induced cycles, even when adjusting for the diagnosis of PCOS. ET was not associated with the odds of achieving a clinical pregnancy, except for couples with idiopathic infertility.

Pregnancy attempts among adolescent and young adult cancer survivors.

OBJECTIVE: To examine whether demographic and cancer-related characteristics and factors such as fertility discussion with a medical provider and fertility preservation use are associated with attempting pregnancy after adolescent and young adult cancer. DESIGN: Cross-sectional online survey. SETTING: Not applicable. PATIENT(S): Women with lymphoma, breast cancer, thyroid cancer, or gynecologic cancer diagnosed at 15-39 years from 2004 to 2016 were identified from the North Carolina Cancer Registry and the Kaiser Permanente Northern and Southern California health care systems and responded to an online survey addressing survivorship concerns, including fertility and reproductive outcomes. EXPOSURES: Demographic characteristics, cancer characteristics, fertility discussion with a medical provider or fertility specialist between cancer diagnosis and starting cancer treatment, use of fertility preservation strategies (freezing embryos or oocytes) after cancer diagnosis. MAIN OUTCOME MEASURE(S): Pregnancy attempt after cancer diagnosis, defined by either a pregnancy or 12 months of trying to become pregnant without pregnancy. RESULT(S): Among 801 participants who had not reached their desired family size at diagnosis, 77% had a fertility discussion with any medical provider between cancer diagnosis and treatment initiation, and 8% used fertility preservation after cancer diagnosis. At survey (median =7 years after diagnosis; interquartile range, 4-10), 32% had attempted pregnancy. Neither fertility discussion with any medical provider nor fertility counseling with a fertility specialist was significantly associated with pregnancy attempts. However, the use of fertility preservation was significantly associated with attempting pregnancy (prevalence ratios = 1.74; 95% confidence interval: 1.31-2.32). Other characteristics positively associated with pregnancy attempts included younger age at diagnosis, longer time since diagnosis, having a partner (at diagnosis or at survey), and having a history of infertility before cancer diagnosis. CONCLUSION(S): Use of fertility preservation strategies was uncommon in our cohort but was associated with attempting pregnancy after cancer. Ensuring access to fertility preservation methods may help adolescent and young adult cancer survivors to plan and initiate future fertility.

Patient-Reported Sexual Function Among Young Adult Cancer Survivors.

Purpose: Reproductive health and sexual function are important to survivors of Adolescent and Young adult (AYA) cancers. We evaluated the prevalence of sexual dysfunction and factors associated with dysfunction using the Patient-Reported Outcomes Measurement Information System (PROMIS) sexual function (SexFS) measure in AYAs (15-39 years old at diagnosis) enrolled in a cancer survivorship cohort. Materials and Methods: Using a cross-sectional survey of a tertiary medical center-based cancer survivorship cohort, we determined the mean PROMIS SexFS v1.0 T-scores and prevalence of scores that were indicative of dysfunction (>1/2 standard deviation [SD] below reference population mean). Multivariable generalized linear regression was performed to identify factors associated with lower scores. Results: We identified 284 AYA cancer survivors, most of whom were women (70%). The mean age at survey was 36.0 years (SD = 7.9). Overall, 31% of females and 19% of men had clinically significantly lower scores than the general U.S. population in the domain of interest, and 13% of women and 6% of men had abnormal scores for satisfaction. Twenty-six percent of male AYAs reported erectile dysfunction. The rate of sexual inactivity in the last 30 days was 27%. Low levels of physical activity were associated with lower PROMIS scores for interest in sexual activity in both men and women, and for global satisfaction with sex life in women only. Conclusions: Our results suggest that low interest in sexual activity is common among survivors of AYA cancers. Low levels of physical activity may be associated with lower levels of interest in and satisfaction with sexual activity in this population.

Optimization of assisted reproductive technology outcomes in patients with polycystic ovarian syndrome: updates and unanswered questions.

PURPOSE OF REVIEW: Narrative review of recent literature on optimization of assisted reproduction technology outcomes in patients with polycystic ovarian syndrome (PCOS). RECENT FINDINGS: The key areas of focus include pre cycle treatment with the goal of cohort synchronization, methods of ovulation suppression and trigger medication. There is no definitive evidence that precycle treatment with combined oral contraceptives (COCs) or progestins improve or negatively impact in vitro fertilization outcomes in patients with PCOS. The reviewed evidence supports consideration of progestins as suppression of premature ovulation in patients with PCOS as an alternative to gonadotropin releasing hormone (GnRH) antagonist if a freeze all protocol is planned. There is limited prospective evidence in PCOS populations regarding use of a dual trigger using GnRH agonist and human chorionic gonadotropin (hCG). SUMMARY: This review has implications for clinical practice regarding ovarian stimulation protocols for patients with PCOS. We also identified areas of research need including the further exploration of the value of pre cycle COC or progestin use in a PCOS population, also the use of GnRH agonist in combination with hCG in a well defined PCOS population and using GnRH agonist trigger alone as a control.

The effect of semen collection at home on intrauterine insemination outcomes.

BACKGROUND: The WHO 2010 guidelines recognize at-home semen collection as an acceptable alternative to standard collection at the clinic in "exceptional circumstances." There is lack of sufficient data to determine the need for revisiting these recommendations for treatment purposes. OBJECTIVES: To determine whether at-home semen collection has any effect on intrauterine insemination (IUI) cycle outcomes. MATERIALS AND METHODS: This is a retrospective cohort study of 729 IUI treatment cycles (382 patients) performed at an academic fertility center from September 19, 2019 to December 31, 2020. Semen collected at the "clinic" was used for 343 cycles before the Coronavirus Disease 2019 (COVID-19) pandemic (September 19, 2019 to March 21, 2020), and "at-home" collected specimens were used for 386 cycles following revised protocols with COVID-19-driven changes (May 30, 2020 to December 31, 2020). Logistic regression models were performed to evaluate the effect of "at-home" semen collection on achieving a positive pregnancy test (PPT) and a clinical pregnancy (CP). RESULTS: Male and female partners' age, ovarian reserve biomarkers, and stimulation regimens used were similar in the "clinic" and "at-home" groups. In unadjusted models, "at-home" collection had no significant effect on the odds for a PPT [OR (95%CI): 0.733 (0.503-1.069)] or CP [0.816 (0.543-1.226)]. These results persisted even when adjusting for maternal age and anti-Müllerian hormone: PPT [0.739 (0.505-1.081)] and CP [0.826 (0.547-1.248)]. Of the semen analysis parameters under evaluation, only motility appeared to significantly impact the odds of achieving a PPT [1.014 (1.004-1.025)] and a CP [1.017 (1.006-1.029)]. This effect was slightly attenuated for samples collected "at-home" [1.012 (0.997-1.027) and 1.015 (0.999-1.031), respectively, for PPT and CP]. DISCUSSION: This study adds important information to the limited literature regarding the effect of at-home semen collection on IUI outcomes. Under adequate protocols, at-home semen collection should be considered a safe alternative. Additional research is needed to optimize such protocols. CONCLUSION: Our data suggest that at-home semen collection does not negatively impact IUI pregnancy outcomes.

Contraceptive use and counseling in patients with systemic lupus erythematosus.

OBJECTIVES: (1) Describe contraception use in women with systemic lupus erythematosus (SLE); (2) characterize the types of contraception used by this population; (3) determine factors affecting the documentation of contraception use; (4) identify if contraception counseling was received in this population at risk for adverse pregnancy outcomes. STUDY DESIGN: This cross-sectional study analyzed data from clinic visits from 2016 - 2018 among 453 women of reproductive age who have SLE. Documentation of contraception use, contraception method, contraception counseling, and other medication use were abstracted from the medical record and analyzed with percentage based statistics, chi-squared test, t-test, and logistic regression. RESULTS: Of the 453 women included in the analysis, 71% had a method of contraception documented within 2 years of the study period. Only 37% were using highly effective contraception. 78% had documentation of contraception counseling. Half (50%) were using teratogenic medications; patients on teratogenic medications had higher odds of having a contraceptive method documented (OR 1.56, 95% CI 1.04 - 2.36) however 24% did not have any contraception documented. 28% of patients were using contraception for which they had a possible or absolute contraindication. CONCLUSIONS: Given a substantial proportion of women with SLE did not have any contraception or contraceptive counseling documented, these findings suggest the need to improve universal reproductive health counseling in patients with SLE. IMPLICATIONS: There is room to improve reproductive health care in patients with SLE through provider training to help optimize pregnancy outcomes in this high-risk population.

The effect of semen collection location and time to processing on sperm parameters and early IVF/ICSI outcomes.

PURPOSE: We aimed to assess whether home collection and increased time to semen processing are associated with altered sperm parameters, fertilization rates (FR), day 5 usable quality blastocyst development rates (D5-UQBR), or pregnancy rates (PR) in patients undergoing IVF/ICSI. METHODS: This was a retrospective cohort study of patients undergoing IVF/ICSI before the coronavirus disease 2019 (COVID-19) pandemic ("clinic" collection, n = 119) and after COVID-19 ("home" collection, n = 125) at an academic fertility practice. Home collection occurred within 2 h of semen processing. Patient sperm parameters, FR (#2PN/MII), D5-UQBR (# transferable and freezable quality blastocysts/# 2PN), and PR in fresh transfer cycles were compared between clinic and home groups with t-tests. The association between time to processing on outcomes was assessed with regression modeling, controlling for potential confounders. RESULTS: Mean male age was 37.9 years in the clinic group and 37.2 years in the home group (p = 0.380). On average, men were abstinent for 3.0 days (SD 1.7) in the clinic group and 4.1 days (SD 5.4) in the home group (p = 0.028). Mean time to semen processing was 35.7 min (SD 9.4) in the clinic group and 82.6 min (SD 33.8) in the home group (p < 0.001). There was no association between collection location and increased time to processing on sperm motility, total motile count, FR, D5-UQBR, or PR. CONCLUSIONS: Our data suggest that increased time to processing up to 2 h with home semen collection does not negatively impact sperm parameters or early IVF/ICSI outcomes.

Karyotype is associated with timing of ovarian failure in women with Turner syndrome.

OBJECTIVE: To characterize the age of ovarian failure in Turner Syndrome (TS) patients by karyotype. METHODS: Retrospective cohort study of individuals with TS at an academic university hospital. Subjects were seen in TS Clinic at UNC Hospital between 2014 and 2018. Individuals were analyzed by karyotype category (45X, 45X/46XX mosaicism, miscellaneous) and percentage of 45X cells. Age at follicle-stimulating hormone> 30 was defined as the age at loss of ovarian function. RESULTS: A total of 79 patients were identified after excluding individuals with unknown ovarian function and those with Y chromosome material. Thirty-eight percent were 45X monosomic, 62% were 45X/46XX mosaic or miscellaneous karyotypes. Fifty-five of 79 (70%) patients had evidence of ovarian failure, median age of failure 11 years (IQR: 4,12). Ovarian failure was more prevalent among individuals with 45X karyotype (100%). The median age of ovarian failure for 45X patients (n=30) was 10 years old, which is significantly younger than other karyotypes (n=49), with a median of 15 years, p<0.01. Linear regression analysis found that 1 percentage point increase in 45X cells in the peripheral karyotype is associated with a 0.09 year decrease in age of ovarian failure (p value=0.01). Only 9% of individuals were referred for fertility counseling. CONCLUSIONS: There is a lower prevalence of ovarian failure among individuals with mosaic TS karyotypes, and referral rate for fertility counseling of patients with TS is low. These findings are in line with published literature. The finding that percentage of 45X cells in peripheral karyotype is associated with earlier age of ovarian failure is novel and warrants further investigation in a larger prospective cohort.

Prevalence of positive screening test for cognitive impairment among elderly urogynecologic patients.

BACKGROUND: Impaired cognition has been correlated with adverse postoperative outcomes, such as an increased incidence of delirium, a longer length of hospital stay, and higher 6 month mortality. The incidence of cognitive impairment in the elderly is high. Per the Centers for Disease Control and Prevention, 1 in 8 adults aged 60 years and older deal with memory loss and confusion, and less than 20% inform their health care providers. Most studies in the elderly or cognitively impaired have been conducted at Veterans Administration hospitals, in which the majority of patients are male. As the female patient population ages, it is increasingly important to describe the prevalence of cognitive impairment in this specific population as well as identify and manage risk factors for cognitive decline in the ambulatory and perioperative setting. OBJECTIVE: The objective of the study was to determine the prevalence of positive screening for cognitive impairment in a urogynecology ambulatory population and to establish the feasibility of using standardized, validated screening questionnaires in a tertiary care setting. STUDY DESIGN: After institutional review board approval, all English-speaking patients 65 years old or older presenting to our ambulatory urogynecology clinic were invited to participate. Cognitive impairment was assessed using both the validated Mini-Cog test and the Eight-Item Interview to Differentiate Aging and Dementia screen for mild dementia. A Mini-Cog score <3 suggests cognitive impairment, whereas an Eight-Item Interview to Differentiate Aging and Dementia score of ≥2 discriminates dementia from normal cognition. Because of the association of depression and cognition in the elderly, the Geriatric Depression Scale (short form of 15 items) was administered, with a score >5 suggesting depression. Demographic and medical history were abstracted from the medical record. RESULTS: A total of 371 subjects were asked to participate (39 were excluded and 37 declined); 295 subjects (79.5%) were included in the study. Mean subject age was 74.5 years, and 96.6% were white, with an average of 4.1 chronic medical comorbidities. Cognitive impairment was identified in all age groups per the Mini-Cog as follows: 65-74 years, 5.3%; 75-84 years, 13.7%; and 85 years and older, 30%. There was a significant difference in the positive screen for cognitive impairment between ages 65-74 vs >75 (P ≤ .001). According to the Eight-Item Interview to Differentiate Aging and Dementia, all 3 age groups perceived themselves to have early cognitive changes: 65-74 years, 25.9%; 75-84 years, 31.9%; and 85 years and older, 40% (P = .231). The most commonly identified areas of impairment were having daily problems with thinking and memory (62%), problems with judgment (52%), and trouble learning new tools or gadgets (44%). There was no difference in the number of patients who screened positive for depression across age groups: 65-74 years, 5.9%; 75-84 years, 6.3%; and 85 years and older, 10% (P = .697). CONCLUSION: In our study population positive screening for cognitive impairment, as measured by validated questionnaires, was prevalent among women aged >75 years. Screening for potential cognitive impairment in an ambulatory urogynecology population is feasible and useful in clinical practice. Our subjects were interested in cognitive screening because a third of them self-reported early cognitive changes. These tools are effective in screening for previously unrecognized impaired cognition, a definitive diagnosis, and hence treatment requires additional evaluation. Future studies could evaluate which screening tools for cognitive impairment would be most helpful in assessing patients prior to surgery in an effort to further decrease perioperative morbidity in elderly woman.