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To determine the ongoing pregnancy rate among patients with infertility with a low antimüllerian (AMH) level compared with those with a normal AMH level after oral and injectable ovulation induction (OI)/intrauterine insemination (IUI).Retrospective cohort.Academic center.Patients completing ≥1 medicated OI/IUI cycle at our center between 2015 and 2019 were included. The AMH levels were measured within 12 months of treatment initiation. The cohort was stratified into low AMH (AMH level,1.0 ng/mL) and normal AMH (AMH level, ≥1.0 ng/mL) groups. All subsequent medicated OI/IUI cycles occurring within 1 year of initial cycle start date were included up to the third completed cycle or until an ongoing pregnancy was recorded. Patients were stratified by age (35, 35-40, and40 years), and the relationship between the low and normal AMH groups and each binary endpoint were quantified as risk ratios using the age-adjusted Poisson models.None.Ongoing pregnancy.A total of 3,122 patients completed 5,539 oral antiestrogen cycles, and 1,060 completed 1,630 injectable gonadotropin cycles. For oral antiestrogen treatment, pregnancy outcomes, including ongoing pregnancy rate per cycle, for patients with a low AMH level were comparable with those for patients with a normal AMH level (35 years, 15.4% vs. 14.9%; 35-40 years, 10.0% vs. 11.0%; and40 years, 2.8% vs. 3.3%). For injectable gonadotropin treatment, the ongoing pregnancy rate was lower in the low AMH group than in the normal AMH group for the ages of35 (12.1% vs. 23.5%; relative risk [RR], 0.52 [95% confidence interval {CI}, 0.28-0.97]) and 35-40 (12.5% vs. 18.5%; RR, 0.70 [95% CI, 0.49-0.99]) years but comparable with that for patients aged40 years (3.0% vs. 4.0%; RR, 0.86 [95% CI, 0.31-2.35]). The proportion of multifetal gestations was similar between the low and normal AMH groups treated with oral antiestrogens (13.1% vs. 10.8%); however, for injectable gonadotropin treatment, patients with a normal AMH level had a higher proportion of multifetal gestations (18.6% vs. 31.1%).Compared with normal ovarian reserve, treatment with oral antiestrogens for OI/IUI for patients with low ovarian reserve results in comparable follicular development and ongoing pregnancy rates for all age groups. When patients with low ovarian reserve are treated with gonadotropins for OI/IUI, multifollicular recruitment is less likely resulting in a significantly decreased ongoing pregnancy rate for patients aged35 and 35-40 years but also a decrease in multifetal gestations. Overall, the ongoing pregnancy rates of 8.7% per oral antiestrogen cycle and 8.1% per injectable gonadotropin cycle in patients with low ovarian reserve are comparable with the expected rates in the general infertility population.

Objective To determine if increasing paternal age has an adverse effect on pregnancy outcomes in paired donor egg recipients who received oocytes from the same donor in the same stimulation cycle. Design Retrospective cohort study. Setting Reproductive Medicine Center. Patient(s) The study included 154 recipients who received oocytes from a split donor oocyte cycle and received sperm from men in discrepant age groups (group A: Intervention(s) None. Main Outcome Measure(s) Implantation rate, pregnancy loss rate, pregnancy rate, and live birth rate. Result(s) The median paternal age was 41 years old for group A and 48 years old for group B. The pregnancy rate was 81% in group A compared with 69% in group B. The live birth rate was 65% in group A compared with 53% in group B. The rate of pregnancy loss was 19% in group A and 23% in group B. The implantation rate was 69% in group A compared with 66% in group B. The adjusted odds of pregnancy were found to be 65% lower for patients in the older partner age group (95% confidence interval [CI], 0.13, 0.95). The adjusted odds of live birth rate (odds ratio [OR], 0.45; 95% CI, 0.20, 1.00), implantation rate (OR, 0.91; 95% CI, 0.43, 1.92), and rate of pregnancy loss (OR, 1.5; 95% CI, 0.5, 4.5) favored the younger partner age group; however, these results were not statistically significant. Conclusion(s) In this model that controlled for oocyte quality to the greatest degree possible by using paired recipients from the same donor from the same stimulation cycle, we found that increased paternal age had a negative effect on pregnancy rates.

Objective To determine if the time from oocyte retrieval to frozen embryo transfer (FET) in the natural cycle affects reproductive or neonatal outcomes. Design Retrospective cohort. Setting Not applicable. Patient(s) Five hundred and seventy-six consecutive freeze-all cycles from January 2011 to December 2018 followed by natural cycle FET of a single blastocyst. Intervention(s) None. Main Outcome Measure(s) Primary outcome of live birth; secondary outcomes of preterm delivery (24–37 weeks) and small for gestational age (SGA) with a multivariable logistic regression performed with adjustment for age, infertility diagnosis, ovulatory trigger type, and preimplantation genetic testing (PGT). Result(s) Before adjustment for confounding, we found a statistically significantly different live-birth rate (57.7% vs. 48.6%) for natural cycle FET occurring in the first versus second menstrual cycle, respectively. In a multivariate analysis, performing a natural cycle FET of a single blastocyst in the second compared with the first menstrual cycle did not statistically significantly impact the odds of live-birth rate. After adjustment for age, diagnosis, and ovulatory trigger type, only PGT was associated with statistically significantly increased odds of live birth compared with no PGT. There were no differences in the incidence of SGA (male, 6.6% vs. 2.3%; female, 9.8% vs. 11.1%) or preterm delivery (1.6% vs. 5.6%) between both groups. Conclusion(s) Performing a natural cycle FET of a single blastocyst in the second compared with the first menstrual cycle after ovarian stimulation did not statistically significantly impact the odds of live birth or neonatal outcomes.

What is the impact of low body mass index (BMI) on live birth rates and obstetric outcomes in infertile women treated with IVF and fresh embryo transfer?This was a retrospective cohort study of infertile patients in an academic hospital setting who underwent their first oocyte retrieval with planned autologous fresh embryo transfer between 1 January 2012 and 31 December 2018. The primary study outcome was live birth rate. Secondary outcomes were IVF treatment and delivery outcomes. Underweight patients were stratified into a significantly underweight group (body mass index [BMI]17.5 kg/mA total of 5229 patients were included (significantly underweight, 76; mildly underweight, 231; normal weight, 4922), resulting in 4798 embryo transfers. After oocyte retrieval, there were no significant differences between groups for total oocytes, mature oocyte yield and number of supernumerary blastocysts cryopreserved. Among women who had an embryo transfer, there were no significant differences in the live birth rates in significantly (31.0%, odds ratio [OR] 0.67, confidence interval [0.95, CI] 0.40-1.13) and mildly (37.7%, OR 0.95, CI 0.73-1.33) underweight patients compared with normal-weight patients (35.9%). Additionally, there were no statistically significant increased risks of preterm delivery, Caesarean delivery or a low birthweight (2500 g) neonate.Mildly and significantly underweight infertile women have similar pregnancy and live birth rates to normal-weight patients after IVF treatment. In addition, underweight patients do not have an increased risk of preterm delivery (37 weeks), Caesarean delivery or a low birthweight neonate.

To assess the association between anti-müllerian hormone (AMH) and embryo ploidy rates in two cohorts of patients undergoing in vitro fertilization (IVF) with trophectoderm biopsy for preimplantation genetic testing for aneuploidy (PGT-A): (1) the general population of women pursuing IVF with PGT-A (Infertile cohort) and (2) women pursuing IVF with preimplantation genetic testing for monogenic disorders (PGT-M) due to risk for hereditary monogenic diseases (Non-infertile cohort).Retrospective cohort study.Academic center.Patients undergoing their first cycle of IVF with trophectoderm biopsy and PGT-A or PGT-A and PGT-M in our center between 03/2012 and 06/2020. Patients of advanced maternal age according to Bologna criteria (age ≥40) and patients who underwent fresh embryo transfers were excluded.None.Proportion of euploid, mosaic, and aneuploid embryos per cycle."Infertile" (n= 926) and "Non-infertile" (n= 214) patients were stratified based on AMH levels, with low AMH defined as1.1 ng/ml in accordance with the Bologna criteria. Age-adjusted regression models showed no relationship between AMH classification and proportion of euploid, mosaic, and aneuploid embryos in the Infertile or Non-infertile cohorts. In the Infertile cohort, no association between AMH classification and embryo ploidy rates was identified in a subgroup analysis of patients less than 35 years, patients 35-37, and patients 38-39 years old. These findings persisted in a sensitivity analysis of Infertile patients stratified into AMH (ng/ml) quartile categories.AMH is not associated with proportion of euploid, mosaic, or aneuploid embryos in two large cohorts of patients undergoing IVF with PGT-A (Infertile patients) or PGT-A and PGT-M (Non-infertile patients), suggesting that a quantitative depletion of ovarian reserve does not predict the ploidy status of the embryo cohort.

PURPOSE: This study sought to identify the initiation of placental hormonal production as defined by the production of endogenous estradiol (E2) and progesterone (P4) in a cohort of patients undergoing programmed endometrial preparation cycles with single embryo transfers resulting in live-born singletons. METHODS: In this retrospective cohort study, patients undergoing either programmed frozen-thawed embryo transfer (FET) with autologous oocytes or donor egg recipient (DER) cycles with fresh embryos were screened for inclusion. Only patients who underwent a single embryo transfer, had a single gestational sac, and a resultant live-born singleton were included. All patients were treated with E2 patches and intramuscular progesterone injections. Main outcome measures were serial E2 and P4, with median values calculated for cycle days 28 (baseline), or 4w0d gestational age (GA), through 60, or 8w4d GA. The baseline cycle day (CD) 28 median value was compared to each daily median cycle day value using the Wilcoxon signed rank test. RESULTS: A total of 696 patients, 569 using autologous oocytes in programmed FET cycles and 127 using fresh donor oocytes, from 4/2013 to 4/2019 met inclusion criteria. Serum E2 and P4 levels stayed consistent initially and then began to increase daily. Compared to baseline CD 28 E2 (415 pg/mL), the serum E2 was significantly elevated at 542 pg/mL (P

The summary presented herein represents Part II of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part II outlines the appropriate management of the male in an infertile couple. Medical therapies, surgical techniques, as well as use of intrauterine insemination (IUI)/in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) are covered to allow for optimal patient management. Please refer to Part I for discussion on evaluation of the infertile male and discussion of relevant health conditions that are associated with male infertility.The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January 2000 through May 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology.This Guideline provides updated, evidence-based recommendations regarding management of male infertility. Such recommendations are summarized in the associated algorithm (figure[Figure: see text]).Male contributions to infertility are prevalent, and specific treatment as well as assisted reproductive techniques are effective at managing male infertility. This document will undergo additional literature reviews and updating as the knowledge regarding current treatments and future treatment options continues to expand.

OBJECTIVE: Assess the effect of class III (body mass index [BMI, kg/m(2)] 40–49.9) and class IV obesity (≥ 50) on clinical pregnancy and live birth outcomes after first oocyte retrieval and fresh embryo transfer cycle. DESIGN: Cohort study SETTING: Academic center PATIENTS: Patients undergoing their first oocyte retrieval with planned fresh embryo transfer in our clinic between 01/01/2012 and 12/31/2018. Patients were stratified by BMI: 18.5–24.9 (n = 4913), 25–29.9 (n = 1566) 30–34.9 (n = 559), 35–39.9 (n = 218), and ≥ 40 (n = 114). INTERVENTION: None MAIN OUTCOME MEASURE: Live birth rate RESULTS: Following embryo transfer, there were no differences in pregnancy rates across all BMI groups (p value, linear trend = 0.86). However among pregnant patients, as BMI increased, a significant trend of a decreased live birth rate was observed (p value, test for linear trend = 0.004). Additionally, as BMI increased, a significant trend of an increased miscarriage rate was observed (p value, linear trend = < 0.001). Compared to the normal-weight cohort, women with a BMI ≥ 40 had a significantly higher rate of cancelled fresh transfers after retrieval (18.4% vs. 8.2%, OR 2.51; 95%CI 1.55–4.08). Among singleton deliveries, a significant trend of an increased c-section rate was identified as the BMI increased (p value, linear trend = 40 have worse IVF treatment outcomes compared to normal-weight patients. After embryo transfer, their pregnancy rate is comparable to normal-weight women; however, their miscarriage rate is higher, leading to a lower live birth rate for pregnant women in this population. Patients with a BMI > 40 have a c-section rate that is 50% higher than normal-weight patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-020-02011-1.

Ectopic pregnancy represents a potentially life-threatening diagnosis. The risk factors for recurrent ectopic pregnancy have been enumerated but are not yet clearly defined. Understanding which risk factors are perhaps more common may allow providers to counsel and manage patients with a higher level of scrutiny.

Objective To determine whether a higher body mass index (BMI) adversely affects endometrial receptivity. Design Retrospective cohort study. Setting Academic medical center. Patient(s) All donor egg recipients (DERs) who received fresh sibling-oocytes (oocytes from a donor that were retrieved from a single controlled ovarian hyperstimulation [COH] cycle and split between two recipients) at our center over a 7-year period were included. Intervention(s) COH of a donor with fresh embryo transfer to recipients of differing BMI. The two recipients of the sibling-oocytes were paired and categorized based on BMI: group A (normal weight, BMI 18.5−24.9 kg/m2) and group B (overweight/obese, BMI >25.0 kg/m2). Main Outcome Measure(s) The primary outcome was implantation rate. Secondary outcomes were positive pregnancy rate and live birth rate. Result(s) A total of 408 patients had received oocytes from a split donor oocyte cycle. There were 71 pairs of patients (142 recipients) that had discrepant BMI categories and were analyzed. Implantation rates were similar for the two groups (54.5%±5.3% vs. 56.3%±4.8% for group A and B, respectively, P=0.72). The positive pregnancy rate (77.5% vs. 80.3%, P=0.28) and live birth rate (54.9% vs. 60.6%, P=0.33) for groups A and B were also found to be similar. Conclusion(s) In this idealized model that controls to the greatest degree possible for factors that would impact implantation, we found that a higher BMI did not reduce implantation, positive pregnancy, or delivery rates. These findings suggest that a higher BMI does not adversely affect uterine receptivity.

Is household income or IVF insurance coverage associated with live birth outcomes in infertile women undertaking IVF?Retrospective cohort study in an academic hospital, including patients residing in New York State undergoing a frozen single embryo transfer at the study IVF centre between 1 January 2017 and 31 December 2018. Only the first embryo transfer per patient was included. Patients were stratified by tertiles of estimated income using home zip code census data:$85,888 (n = 348), $85,888-122,628 (n = 348) and$122,628 (n = 350). A second analysis stratified patients by IVF insurance coverage or no coverage. The primary outcome was live birth. Modified Poisson regression with robust error variance adjusted a priori for age, preimplantation genetic testing and previous fresh embryo transfer estimated the relative risk of outcomes with a 95% confidence interval.A total of 1046 patients were included. Live birth rate was similar among all three income tertiles. Secondarily, the pregnancy rate and pregnancy loss rate were also similar among all three tertiles. In the IVF insurance coverage analysis, live birth rate was similar between patients with and without IVF insurance coverage. Secondarily, the pregnancy rate and pregnancy loss rate were also similar among these two groups.Overall, neither median household income nor IVF insurance coverage of patients undergoing single frozen embryo transfer was associated with pregnancy, pregnancy loss or live birth outcomes. Lower income, relative to the patient cohort, and lack of insurance coverage are well-described barriers to accessing infertility evaluation and treatment. However, once treatment is initiated, the current results suggest that these variables do not influence pregnancy and live birth outcomes in infertile patients.

PURPOSE: To identify biomarkers that prospectively predict IVF cycle cancellation. METHODS: In this prospective study, sera were obtained prior to any intervention, from women about to undergo an IVF cycle. The sera were assayed by ELISA for levels of insulin-like growth factor (IGF)-1, IGF-2, IGF binding protein (BP)-1, and soluble fms-like tyrosine kinase (sFLT-1). The cancellation or progression of the IVF cycle was subsequently obtained by chart review. Associations between serum components and outcome were analyzed by the Mann-Whitney test. Receiver operator curves were constructed to evaluate the strength of the correlations between biomarkers and cycle cancellation, as assessed from the area under the curve (AUC). RESULTS: A total of 205 women were included. Twenty-seven (13.2%) cycle cancellations due to poor response were recorded. Women with a cancelled cycle had reduced anti-Mullerian hormone (AMH) values (p < 0.001) and antral follicle count (p = 0.003). There were no significant differences between the two groups with regard to age and BMI. Median concentrations of IGF-1 and sFLT-1 were elevated in sera from women whose IVF cycles were cancelled as compared to those with ongoing cycles (p = 0.015 and p < 0.001, respectively); AUC for IGF-1 and sFLT-1 were 0.67 and 0.75, respectively. Concentrations of sFLT-1 remained significantly higher in patients with cancelled cycles even after controlling for AMH levels. There were no differences in IGF-2 and IGFBP-1 levels between the two groups. CONCLUSIONS: Measurement of circulating IGF-1 and sFLT-1 levels prior to initiation of an IVF cycle has the potential to identify women whose cycles have an increased likelihood to be subsequently cancelled.

Objective To assess right–left differences in ultrasonographic markers of ovarian morphology and determine the impact on the diagnosis of polycystic ovarian morphology (PCOM). Design A cross-sectional study of data collected from 2006 to 2018. Setting Academic clinical research centers. Patient(s) Women with polycystic ovary syndrome (PCOS; n = 87) and controls (n = 67). Intervention(s) None. Main Outcomes Measure(s) Follicle number per ovary (FNPO), follicle number per cross-section (FNPS), and ovarian volume (OV) were assessed in both ovaries using transvaginal ultrasonography. PCOM was identified based on recent international consensus guidelines or proposed diagnostic thresholds. Result(s) Overall, mean right–left differences were two follicles for FNPO, one follicle for FNPS, and 2 mL for OV. FNPO showed the strongest correlation between ovaries. Its assessment in a single ovary did not impact the diagnosis of PCOM in women with PCOS. However, there were differences in the probability of unilateral versus bilateral PCOM based on FNPS and OV in both groups. Conclusion(s) FNPO is the most reliable unilateral marker of PCOM in light of right–left differences in ovarian morphology. Use of FNPS or OV to define PCOM is discouraged when only one ovary is visualized.

Research question Do IVF-ICSI cycles using fresh and frozen ejaculated sperm result in similar pregnancy outcomes in couples with non-male factor infertility? Design In a retrospective cohort study, patients undergoing donor egg recipient cycles in which oocytes from a single controlled ovarian hyperstimulation were split between two recipients were reviewed. Two recipients of the single donor oocyte were paired and categorized based on the type of ejaculated sperm (fresh/frozen). Outcomes included live birth rate (LBR), implantation, pregnancy, pregnancy loss and fertilization rates. Results 408 patients received oocytes from a split donor oocyte cycle. 45 pairs of patients used discrepant types of ejaculated sperm. Fertilization rate was 74.8% in the fresh and 68.6% in the frozen sperm group (p=0.13). Pregnancy rate was 76% in the fresh and 67% in the frozen group. LBR was 69% in the fresh and 44% in the frozen group. Implantation rate was significantly higher at 64% in the fresh and 36% in the frozen group (p=0.04). Rate of pregnancy loss was significantly higher at 5.9% in the fresh and 33% in the frozen group (p = 0.013). Adjusted odds of LBR was 67% lower for patients in the frozen group (95% CI: 0.12, 0.89). Adjusted odds of pregnancy (OR 0.67, 95% CI: 0.20, 2.27) and implantation rates (OR 0.5, 95% CI: 0.12, 2.12) favored the fresh group. Conclusion In this model that controls for oocyte quality by using paired recipients from the same donor, we found that frozen ejaculated sperm resulted in lower live birth rates than those using fresh sperm.

Gestational surrogacy in the United States has quadrupled since 1999, but to date, only a few states explicitly permit compensated gestational surrogacy. Current legal prohibitions are often influenced by outdated and stereotyped understandings of surrogacy. It is increasingly important to understand the current literature about the medical and mental health impacts of surrogacy and how state legislatures have addressed compensated gestational surrogacy in recent years. Based on this review, we found no evidence of substantial adverse medical or psychological outcomes among women who are gestational carriers or among the children they give birth to. The literature suggests that gestational surrogacy is a safe and increasingly popular option for families as long as rigorous screening and medical, psychological, and social supports are equitably provided. As states move to responsibly legalize and regulate gestational surrogacy, there is a continued need for further longitudinal studies on the health and psychological outcomes of gestational surrogacy.

Purpose The summary presented herein represents Part I of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part I outlines the appropriate evaluation of the male in an infertile couple. Recommendations proceed from obtaining an appropriate history and physical exam ( Appendix I ), as well as diagnostic testing, where indicated. Materials/Methods The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January, 2000 through May, 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. ( Table 1 ) This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. Results This Guideline provides updated, evidence-based recommendations regarding evaluation of male infertility as well as the association of male infertility with other important health conditions. The detection of male infertility increases the risk of subsequent development of health problems for men. In addition, specific medical conditions are associated with some causes for male infertility. Evaluation and treatment recommendations are summarized in the associated algorithm. ( Figure 1 ) Conclusion The presence of male infertility is crucial to the health of patients and its effects must be considered for the welfare of society. This document will undergo updating as the knowledge regarding current treatments and future treatment options continues to expand.

Objective To assess the association between body mass index (BMI) and embryo aneuploidy and mosaicism in a cohort of patients undergoing in vitro fertilization (IVF) with trophectoderm biopsy for preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing technology. Design Retrospective cohort study. Setting Academic center. Patients Patients undergoing their first IVF cycle with trophectoderm biopsy and PGT-A at our center between January 1, 2017, and August 31, 2020. Patients classified as underweight on the basis of BMI (BMI Intervention None. Main Outcome Measures Number and proportion of aneuploid, mosaic, and euploid embryos. Results The patients were stratified according to the World Health Organization’s BMI classification: normal weight (18.5–24.9 kg/m2, n = 1,254), overweight (25–29.9 kg/m2, n = 351), and obese (≥30 kg/m2, n = 145). Age-adjusted regression models showed no relationship between BMI classification and the number or proportion of aneuploid embryos. There were no statistically significant associations between BMI classifications and the number or proportion of mosaic or euploid embryos. A subgroup analysis of patients classified into age groups of 40 years similarly showed no relationships between BMI and embryo ploidy outcomes. Conclusion Body mass index was not associated with the number or proportion of aneuploid, mosaic, or euploid embryos in this large cohort of patients undergoing IVF with PGT-A, suggesting that the negative effect of excess weight on reproductive outcomes was independent of the ploidy status of the embryo cohort.

The relationship between diet quality and ovarian morphology has biological plausibility yet remains unclear and was therefore evaluated. In a multicenter cross-sectional analysis, four dietary patterns were scored for 111 consecutive reproductive-aged women (18&ndash, 45 years) using (1) Healthy Eating Index (HEI-2015), (2) alternative HEI-2010, (3) alternate Mediterranean Diet (aMED), (4) and Dietary Approaches to Stop Hypertension (DASH) indices. Ovarian volume (OV) and follicle number per ovary (FNPO) were evaluated on transvaginal ultrasonography. Relationships between dietary and ovarian morphology indices were evaluated by linear regression and mediation analyses. Associations between aMED and DASH scores and OV/FNPO were completely mediated by obesity, insulin resistance, and hyperandrogenism (All: p &lt, 0.05), unlike direct associations (All: p &ge, 0.89). Namely, a 1-standard deviation [SD] increase in aMED score was associated with decreases in OV (0.09 SD, 0.4 mL) through reducing waist circumference. Likewise, a 1 SD increase in aMED and DASH score was associated with decreases in OV (0.07 SD, 0.3 mL) by reducing glucose response to a 75 g glucose tolerance test. A 1 SD increase in DASH score was associated with decreased FNPO (0.07 SD, 2 follicles) by reducing free androgen index (All: p &lt, 0.05). Adherence to aMED and DASH eating plans was indirectly associated with significant improvements in ovarian form, providing novel mechanistic insights for future interventions about contributions of diet quality on ovarian function.

Osteosarcopenia is defined by the loss of skeletal muscle and bone mass and/or function usually associated with aging. Osteosarcopenia shares common risk factors and pathophysiological mechanisms with polycystic ovary syndrome (PCOS), including obesity and endocrine aberrations. Relationship between osteosarcopenia and PCOS has biological plausibility yet remains unclear. We hypothesized (1) reproductive-aged women with PCOS would exhibit early signs of osteosarcopenia evidenced by decreased appendicular skeletal muscle index (appendicular skeletal muscle mass/weight (kg) × 100 = SMI%), and bone mineral density (BMD); and (2) SMI% and BMD are aggravated by endocrine disruptions in PCOS. The SMI% and BMD of 203 women (18 – 48 y) were compared across 4 groups: (1) PCOS (hyperandrogenism and oligoamenorrhea), (2) hyperandrogenism and eumenorrhea (HA), (3) normoandrogenic oligoamenorrhea (OA), and (4) Controls. Associations between endocrine measures and SMI% and BMD were evaluated by partial correlations and all comparisons were adjusted for age and obesity. Women with PCOS exhibited reduced total SMI% (mean [95% confidence interval]; 26.2% [25.1 – 27.3] vs. 28.8% [27.7 – 29.8]), lower-extremity SMI% (LESMI%; 57.6% [56.7 – 60.0] vs. 62.5% [60.3 – 64.6]), and total BMD (1.11 [1.08 – 1.14] vs. 1.17 [1.14 – 1.20] g/cm2) compared to Controls. Women with PCOS also had decreased upper (0.72 [0.70 – 0.74] vs. 0.73 [0.71 – 0.76] g/cm2) and lower (1.13 [1.10 – 1.16] vs. 1.15 [1.12–1.18] g/cm2) limb BMD compared to the HA group. Insulin sensitivity evidenced by Matsuda index was declined in PCOS group compared to Controls, yet was positively associated with SMI% in all groups (All: P ≤ 0.05). The OA group exhibited exaggerated insulin-like-growth-factor-1 (IGF-1) compared to Controls (P = 0.01) that had negative associations with LESMI% (r = -0.90; P < 0.01). Only Controls showed positive associations between IGF-1 and upper (r = 0.84) and lower (r = 0.72) limb BMD (All: P < 0.01). Unlike PCOS group, estradiol (r = 0.64) and the ratio of luteinizing hormone to follicle-stimulating hormone (r = 0.54) were positively associated with BMD (All: P < 0.05) in OA group. Also, unlike PCOS group, IGF binding protein-2 (IGFBP-2) was positively associated with muscle or bone mass in other groups. Specifically, IGFBP2 was associated with SMI% in Controls (r = 0.45) and HA (r = 0.67), with LESMI% in OA (r = 0.91), and with upper limb BMD (r = 0.98) in HA groups (All: P < 0.05). Reproductive-aged women with PCOS exhibited early signs of osteosarcopenia likely owing to their unique metabolic and endocrine alterations. Perturbations in insulin signaling and function may drive muscle and bone loss in PCOS. Understanding the biological mechanisms and management strategies that may delay or prevent the development of osteosarcopenia is recommended to improve the musculoskeletal health and associated long-term comorbidities of PCOS.

Introduction: Sonographic evidence of polycystic ovarian morphology (PCOM) is a cardinal feature of polycystic ovary syndrome (PCOS), a condition which reflects a spectrum of phenotypes. The criteria to define PCOM are based on an upper threshold for follicle number and ovarian size in lean, regularly cycling women. Whether ovarian features can be used to distinguish between distinct anovulatory conditions is unclear, as is any impact of body mass index (BMI) on the diagnostic performance of ovarian morphology for anovulatory conditions. Objectives: To determine whether ovarian morphology can discriminate between women with regular cycles, normoandrogenic anovulation (NA-Anov), and hyperandrogenic (HA-Anov) anovulation. Any impact of BMI-specific thresholds to improve the diagnostic performance of ovarian morphology for anovulatory conditions was determined. Methods: Women with HA-Anov (biochemical and/or clinical hyperandrogenism and irregular cycles; N=53), NA-Anov (irregular cycles in the absence of hyperandrogenism; N=42), and normoandrogenic women with regular cycles (Controls, N=41) underwent a reproductive health history, physical exam, transvaginal ultrasound scan of their ovaries and fasting blood tests for reproductive hormones. Follicle number per ovary (FNPO, 2-9mm) and ovarian volume (OV) were determined. The diagnostic performance of sonographic markers for anovulatory conditions was tested using receiver operating characteristic curves. Results: FNPO and OV discriminated between HA-Anov and Controls when all women were considered (area under the curve [AUC]=0.82, sensitivity [Se] 72%, specificity [Sp] 90% and AUC=0.84, Se 77%, Se 81%, respectively). The diagnostic accuracy (AUC = 0.87) and sensitivity (83%) of FNPO improved in lean women (BMI < 25kg/m2), whereas specificity (93%) improved for women with overweight/obesity (BMI > 25kg/m2). By contrast, the diagnostic performance of OV declined when BMI was considered. FNPO discriminated between HA-Anov and NA-Anov in lean women (AUC=0.77) whereas OV discriminated between anovulatory conditions in women with overweight or obesity (AUC=0.76). FNPO, but not OV, differentiated between NA-Anov and controls – albeit thresholds were lower for women in lean (>22 follicles) versus overweight categories (>38 follicles). Conclusion: Ovarian morphology has diagnostic potential for anovulatory conditions – but its performance is impacted by BMI status. OV differentiated between HA and NA status, whereas follicle counts discriminated anovulatory conditions from controls suggesting differential roles for FNPO and OV in reproductive dysfunction. Consideration of BMI improved diagnostic performance in some cases, however the overlap in morphological features between NA- and HA-Anov is too extensive to propose condition-specific thresholds at this time.

An elevated level of insulin growth factor (IGF-1) in rat uterine fluid has been shown to exert detrimental effects of embryo development possibly leading to an increase in pregnancy loss. Interestingly, the administration of somatostatin to rats undergoing superovulation reduced IGF-1 levels in uterine luminal fluid and thus reversed its deleterious effects on embryo development and increased the number of normal embryos. Therefore, we investigated whether serum levels of IGF-1 correlate with the incidence of pregnancy loss following IVF. To account for aneuploidy and the effect of hormonal supplementation on serum IGF levels, we only included natural frozen-thawed euploid embryo transfer (N-FET) cycles. Sera collected in the follicular phase (cycle day 10) were tested for levels of IGF-1, IGF-2, and IGF-binding protein 1 (IGFBP-1) using quantitative ELISA. A total of 156 N-FET cycles were included: 120 resulted in a live birth whereas 36 led to a first trimester pregnancy loss. Women with a pregnancy loss had significantly higher serum IGF-1 levels compared to those who achieved a live birth (18.0 ± 1.1 vs. 14.6 ± 0.7 ng/mL, respectively). The two groups had comparable serum IGF-2 and IGFBP-1 levels. There was no significant difference in maternal age, body mass index, gravidity, parity, number of prior miscarriages, peak endometrial thickness, or infertility diagnosis between the two groups. In conclusion, women undergoing euploid blastocyst transfer with elevated serum IGF-1 concentrations may be at increased risk of pregnancy loss. This may constitute a novel molecular explanation of pregnancy loss of euploid conceptus.

The magnitude and direction to which cardio-metabolic and reproductive aberrations may disproportionately impact diverse populations of women with PCOS are relevant yet unclear. The uncertainty stems, in part, from heterogeneity in PCOS diagnostic criteria used and technical challenges in the reliable assessment of this clinical population. We evaluated whether cardio-metabolic (abdominal adiposity, hypertension, impaired glucoregulatory status) and reproductive (hyperandrogenism, polycystic ovarian morphology [PCOM], menstrual irregularity) outcomes were different in PCOS (n = 120, 18-36 yrs.) across 4 groups: (1) Non-Hispanic White (n = 76); (2) Non-Hispanic Black (n = 14); (3) Non-Hispanic Asian (n = 15); and, (4) Hispanic White (n = 15). Women were prospectively recruited across 3 academic medical centers in New York State and were matched for age and body mass index. PCOS was defined by the Rotterdam criteria using the recommended thresholds of the 2018 International Evidence-based Guideline for the Assessment and Management of PCOS. Concerning abdominal adiposity, the Asian group (mean ± standard deviation; 0.78 ± 0.06) had a lower waist to hip ratio (WHR) compared to the White group (0.85 ± 0.09; P = 0.01). Also, the Asian group had a higher sex hormone binding globulin (SHBG, 65.9 ± 23.4 nmol/L) compared to all other groups (White [40.5 ± 22.3]; Black [43.8 ± 21.9]; Hispanic [36.8 ± 18.8] nmol/L; All: P < 0.04). In contrast, the White group were most hyperandrogenic, evidenced by their higher modified Ferriman-Gallwey (mFG) scores (10 ± 4) compared to other groups (Black [4 ± 0]; Asian [2 ± 0]; Hispanic [4 ± 1]; All: P ≤ 0.001). Consistently, the White group (1.0 ± 0.5 ng/dL) exhibited increased free testosterone (FT) compared to other groups (Black [0.5 ± 0]; Asian [0.4 ± 0]; Hispanic [0.6 ± 0.1] ng/dL; All: P ≤ 0.001), unlike total testosterone (P = 0.12). Regarding PCOM, the White group exhibited higher follicle numbers per ovary (FNPO 2-9 mm, 48 ± 22) compared to other groups (Black [30 ± 16]; Asian [26 ± 5]; Hispanic [22 ± 17]; All: P ≤ 0.05). Unlike Black (12.4 ± 1.3 mm; P = 0.05) and Hispanic (13.5 ± 1.1 mm; P = 0.89) groups, the White group (13.9 ± 2.1 mm) also exhibited larger ovarian volume (OV) compared to Asian group (12.4 ± 1.5 mm; P = 0.03). Women had comparable blood pressure (systolic, diastolic), fasting glucose, homeostatic model assessment of insulin resistance, or intermenstrual interval length (All: P ≥ 0.09). Overall, Asian women in the US likely exhibit the mildest PCOS metabolic (decreased WHR, increased SHBG) phenotype, whereas White women show the most severe reproductive (increased mFG, FT, FNPO, OV) phenotype. If confirmed by larger studies, our observations warrant additional population-specific diagnostic considerations to prevent and manage PCOS cardio-metabolic (e.g., metabolic syndrome risk) and reproductive (e.g., hirsutism, PCOM) complications across ethnicities.