Trophectoderm grade as a predictor of beta human-chorionic gonadotropin rise in early pregnancy.

PURPOSE: To evaluate the association, if any, between the grade of the trophectoderm (TE) and the rate at which ß-human-chorionic gonadotropin (ß-HCG) rises in early pregnancy. METHODS: This is a retrospective cohort study including 1116 singleton clinical pregnancies resulting from in vitro fertilization with single day 5 blastocyst transfer at an academic fertility center. TE quality was assessed by trained embryologists employing standard criteria. Three groups were formed based on the TE grade: grade A (n = 358), grade B (n = 628), and grade C (n = 130). Main outcome measure was the rise (%) in serum levels of ß-HCG (days 12 to 14 post embryo transfer), using the following formula [(ß-HCG D14 - ß-HCG D12) * 100/ß-HCG D12]. RESULTS: Fresh embryo transfers accounted for 64.1% of the population. Overall, in adjusted models there were no significant differences in the ß-HCG% rise when comparing the TE grade C group to TE grade A [adjß (95%CI): 10.09 (- 0.05, 20.22)] or when comparing TE grade Β group to TE grade A [4.46 (- 2.97, 11.88)]. When the analysis was restricted to fresh embryo transfers, significant differences were observed in the % rise of ß-HCG when comparing the TE grade C group to TE grade A [adjß (95%CI): 21.71 (5.67, 37.74)], but not when comparing the TE grade B group to TE grade A [2.68 (- 5.59, 10.95)]. In frozen transfers, there were no significant differences. CONCLUSION: TE grade appears to impact early pregnancy serum ß-HCG levels in the setting of a fresh day 5 embryo transfer, even after adjusting for potential confounders.

Prevalence and correlates of diagnosed and probable polycystic ovary syndrome (PCOS) in a cohort of parous women.

OBJECTIVES: To assess correlates of diagnosed and probable polycystic ovary syndrome (PCOS) among parous women. METHODS: This study includes 557 women recruited from multi-specialty clinics in eastern Massachusetts. We categorized women as "diagnosed PCOS" based on medical records and self-reported clinician-diagnoses. Next, we constructed a category of "probable PCOS" for women without a diagnosis but with ≥2 of the following: ovulatory dysfunction (cycle length<21 or ≥35 days), hyperandrogenism (free testosterone>75th percentile), or elevated anti-Müllerian hormone (>75th percentile). We classified the remaining as "no PCOS," and compared characteristics across groups. RESULTS: 9.7% had diagnosed and 9.2% had probable PCOS. The frequency of irregular cycles was similar for diagnosed and probable PCOS. Free testosterone and AMH were higher for probable than diagnosed PCOS. Frequency of irregular cycles and both hormones were higher for the two PCOS groups vs. the no PCOS group. Obesity prevalence for diagnosed PCOS was twice that of probable PCOS (43.9% vs. 19.6%), yet the two groups had similar HbA1c and adiponectin. CONCLUSIONS: Women with probable PCOS are leaner but have comparable glycemic traits to those with a formal diagnosis, highlighting the importance of assessing biochemical profiles among women with irregular cycles, even in the absence of overweight/obesity.

Associations of anti-Müllerian hormone levels among women in their mid-30s with menopausal symptoms ~14 years later.

OBJECTIVE: The aim of this study was to examine associations of anti-Müllerian hormone (AMH) levels in gravid women in their mid-30s with menopausal symptoms ~14 years later and age at natural menopause. METHODS: In this prospective analysis, 474 participants in Project Viva, a longitudinal cohort, were enrolled during pregnancy between 1999 and 2002. AMH levels were determined using plasma samples collected 3 years postpartum. Participants completed the Menopause Rating Scale (MRS) and self-reported age at and reason for menopause at the 17 years postpartum visit (Mid-Life Visit). Primary outcomes were individual MRS item responses and total MRS score. To examine associations between AMH levels and menopausal outcomes, we performed linear and logistic regressions, and survival analyses, adjusting for confounding variables. RESULTS: Mean (SD) AMH level was 2.80 (2.74) ng/mL, measured at 38.2 (3.9) years. At the Mid-Life Visit, mean (SD) age was 52.3 (3.9) years and total MRS score was 8.0 (5.7). During follow-up, 50% had experienced natural menopause, and self-reported mean (SD) age at natural menopause was 50.4 (3.6) years. AMH in the lowest tertile (mean [SD]: 0.47 [0.32] ng/mL) was associated with higher odds of moderate to severe vaginal dryness (adjusted odds ratio: 2.58; 95% CI: 1.16 to 5.73), a lower MRS psychological subscale (adjusted ß: -0.71; 95% CI: -1.35 to -0.07), and earlier attainment of natural menopause (adjusted hazards ratio: 7.1; 95% CI: 4.6 to 11.0) compared with AMH in the highest tertile (mean [SD]: 6.01 [2.37] ng/mL). CONCLUSIONS: Lower AMH in the mid-30s was associated with earlier menopause and increased odds of vaginal dryness but fewer psychological symptoms ~14 years later.

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.

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.

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.

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.

Universal convergence of the specific volume changes of globular proteins upon unfolding.

Both pressure and temperature are important environmental variables, and to obtain a complete understanding of the mechanisms of protein folding, it is necessary to determine how protein stability is dependent on these fundamental thermodynamic parameters. Although the temperature dependence of protein stability has been widely explored, the dependence of protein stability on pressure is not as well studied. In this paper, we report the results of the direct thermodynamic determination of the change in specific volume (DeltaV/V) upon protein unfolding, which defines the pressure dependence of protein stability, for five model proteins (ubiquitin, eglin c, ribonuclease A, lysozyme, and cytochrome c). We have shown that the specific volumetric changes upon unfolding for four of the proteins (ubiquitin, eglin c, ribonuclease A, and lysozyme) appear to converge to a common value at high temperatures. Analysis of various contributions to the change in volume upon protein unfolding allowed us to put forth the hypothesis that the change in volume due to hydration is very close to zero at this temperature, such that DeltaV/V is defined largely by the total volume of cavities and voids within a protein, and that this is a universal property of all small globular proteins without prosthetic groups. To test this hypothesis, additional experiments were performed with variants of eglin c that had site-directed substitutions at two buried positions, to create an additional cavity in the protein core. The results of these experiments, coupled with the structural analysis of cytochrome c showing a lower packing density compared to those of the other four proteins, provided further support for the hypothesis. Finally, we have shown that the deviation of the high-temperature DeltaV value of a given protein from the convergence value can be used to determine the size of the excess cavities in globular proteins.