Polycystic ovary syndrome preceding the diagnosis of acromegaly: a retrospective study in 97 reproductive-aged women.

BACKGROUND: Acromegaly is a disease of growth hormone excess that results in enlargement of extremities, abnormal glucose and lipid metabolism, and gonadal disruption. Manifestations of the disease are insidious and typically lead to a diagnostic delay of 7-10 years. Classically the polycystic ovary syndrome (PCOS) phenotype is described in women with irregular menses, clinical or biochemical evidence of androgen excess, and/or multiple ovarian follicles on pelvic ultrasonography. Women with acromegaly may present with some or all of these symptoms. Our objective was to evaluate the prevalence of PCOS in patients with acromegaly and to determine if diagnosis of PCOS results in a delay in diagnosing acromegaly. METHODS: Using patient databases at two academic health centers, we identified 97 premenopausal women aged 18-49 years old presenting with acromegaly. Data were collected regarding pelvic sonography and reproductive history, including the diagnosis of PCOS. Patients carrying the diagnosis of PCOS before their diagnosis of acromegaly were identified and the remaining patients were screened using the Rotterdam criteria to identify additional patients meeting the criteria for PCOS prior to their diagnosis of acromegaly. RESULTS: Mean age of the population (n = 97) at the time of diagnosis of acromegaly was 33.4 ± 7.5 years (SD). Thirty-three percent of patients (n = 32) either carried a diagnosis of PCOS or met diagnostic criteria for PCOS before their diagnosis of acromegaly. In the subset of patients in whom data on symptom onset were available, those who met criteria for PCOS were diagnosed with acromegaly a median of 5 years [4, 9] after the onset of symptoms compared to 2 years [0.92, 3] (p = 0.006) in the patients who did not meet criteria for PCOS. CONCLUSIONS: Our data demonstrate a high prevalence of signs and symptoms of PCOS in reproductive-aged women with acromegaly and a longer time to diagnosis in women who meet the clinical criteria for PCOS. As screening for acromegaly is relatively simple and done with measurement of a random, non-fasting IGF-1 level that can be drawn at any time during the menstrual cycle, screening patients with PCOS for acromegaly may lessen the delay in diagnosis for reproductive-aged women with this disease.

Evaluation of at-home serum anti-Müllerian hormone testing: a head-to-head comparison study.

BACKGROUND: For optimal fertility testing, serum anti-Müllerian hormone levels are used in combination with other testing to provide reliable ovarian reserve evaluations. The use of the ADx 100 card is widely commercially available for at-home reproductive hormone testing, but data demonstrating that its results are reproducible outside of a clinical setting are limited, as well as comparisons of its performance with other newer blood collection techniques. This study aimed to evaluate the concordance of serum AMH levels found via standard venipuncture and self-administered blood collection using the TAP II device (TAP) and ADx card in women of reproductive age. METHODS: This was a prospective, head-to-head-to-head within-person crossover comparison trial that included 41 women of reproductive age (20-39 years). It was hypothesized that the TAP device would be superior to the ADx card both in terms of agreement with venipuncture reference standard and patient experience. Each subject had their blood drawn using the three modalities (TAP, ADx, and venipuncture). We evaluated the concordance of AMH assays from samples obtained via the TAP device and ADx card with the gold standard being venipuncture. Two-sided 95% CIs were generated for each method to compare relative performance across all three modes. Patient preference for the TAP device versus the ADx card was based on self-reported pain and Net Promoter Score (NPS). RESULTS: The TAP device was superior to the ADx card on all outcome measures. TAP R-squared with venipuncture was 0.99 (95% CI 0.99, > 0.99), significantly higher than the ADx card, which had an R-squared of 0.87 (95% CI 0.80, 0.94) under most favorable treatment. TAP sensitivity and specificity were both 100% (no clinical disagreement with venipuncture), versus 100 and 88%, respectively, for the ADx card. Average pain reported by users of the TAP device was significantly lower than the ADx card (0.75 versus 2.73, p < 0.01) and the NPS was significantly higher than the ADx card (+ 72 versus - 48, p < 0.01). CONCLUSIONS: The TAP was non-inferior to venipuncture and superior to the ADx card with respect to correlation and false positives. Moreover, the TAP was superior to both alternatives on patient experience. TRIAL REGISTRATION: NCT04784325 (Mar 5, 2021).

PCOS and the risk of pre-eclampsia.

RESEARCH QUESTION: What is the association between polycystic ovary syndrome (PCOS) and pre-eclampsia? Data suggest that patients with PCOS are at increased risk of developing pre-eclampsia; however, several studies have not found an independent association between the two. DESIGN: A retrospective case-control study of singleton deliveries at a tertiary care hospital from 2011 to 2015. Patients with pre-eclampsia (cases) were matched to the next delivery without pre-eclampsia (controls) on gestational age week. Medical history data, a diagnosis or clinical features of PCOS and obstetric data, including pre-eclampsia, were abstracted from the medical record. Groups were compared with the chi-squared test, and conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). OR were adjusted for maternal age at delivery and race/ethnicity. RESULTS: This study included 435 cases and 435 controls. Cases were more likely to be Black compared with controls. Age, comorbidities, features of PCOS and use of IVF were similar between groups. Patients with pre-eclampsia were not more likely to have PCOS (8.3%) than those without pre-eclampsia (6.2%, adjusted OR 1.40, 95% CI 0.81-2.30). Sensitivity analyses for body mass index and parity suggested an increased pre-eclampsia risk for patients with PCOS and these additional factors, however no group showed a statistically significant association between PCOS and pre-eclampsia. CONCLUSIONS: In this study, a history of PCOS was not associated with the risk of pre-eclampsia. Further investigation is necessary to determine whether there are subgroups of PCOS patients who are at increased risk of pre-eclampsia.

Lower antimüllerian hormone is associated with lower oocyte yield but not live-birth rate among women with obesity.

BACKGROUND: Antimüllerian hormone is produced by small antral follicles and reflects ovarian reserve. Obesity is associated with lower serum antimüllerian hormone, but it is unclear whether lower levels of antimüllerian hormone in women with obesity reflect lower ovarian reserve. OBJECTIVE: To determine whether lower antimüllerian hormone in women with obesity undergoing in vitro fertilization is associated with oocyte yield and live-birth rate. MATERIALS AND METHODS: Retrospective cohort from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database of 13,316 women with obesity and 16,579 women with normal body mass index undergoing their first autologous in vitro fertilization with fresh transfers between 2012 and 2014. Normal body mass index was defined as body mass index 18.5-24.9 kg/m2, and obesity was defined as body mass index ≥30 kg/m2. Subjects with obesity were stratified as those with class 1 obesity (body mass index, 30.0-34.9 kg/m2), class 2 obesity (body mass index, 35.0-39.9 kg/m2), and class 3 obesity (body mass index, ≥40 kg/m2) based on the World Health Organization body mass index guidelines. Antimüllerian hormone levels were stratified as normal (>1.1 ng/mL), low (0.16-1-1 ng/mL), and undetectable (≤0.16 ng/mL). Multivariable modeling was used to assess oocyte yield using linear regression with a logarithmic transformation and odds of live birth using logistic regression. RESULTS: Women with obesity were older (36.0 ± 4.8 vs 35.5 ± 4.8, P < .001), had lower antimüllerian hormone (1.8 ± 2.0 ng/mL vs 2.1 ± 2.0 ng/mL, P < .001), and had fewer oocytes retrieved (11.9 ± 7.3 vs 12.8 ± 7.7, P < .001) than women with normal body mass index. Lower oocyte yield was observed among women with obesity and normal antimüllerian hormone levels compared to women with normal body mass index and normal antimüllerian hormone levels (13.6 ± 7.3 vs 15.8 ± 8.1, P < .001). No difference in oocyte yield was observed among women with obesity and low antimüllerian hormone levels (P = .58) and undetectabl antimüllerian hormone (P = .11) compared to women with normal BMI and similar antimüllerian hormone levels. Among women with a body mass index ≥30 kg/m2, antimüllerian hormone levels were associated with the number of oocytes retrieved (ß = 0.069; standard error, 0.005; P < .001) but not live-birth rate (odds ratio, 0.98; 95% confidence interval, 0.93-1.04, P = .57). CONCLUSION: Lower antimüllerian hormone in infertile women with obesity appears to reflect lower ovarian reserve, as antimüllerian hormone is associated with lower oocyte yield. Despite lower oocyte yield, lower antimüllerian hormone was not associated with lower live-birth rate among women with obesity.

Predictors of reproductive outcomes following myomectomy for intramural fibroids.

RESEARCH QUESTION: Which factors are associated with reproductive outcomes among infertile women undergoing myomectomy for intramural fibroids? DESIGN: This was a historical cohort study including 127 infertile women who underwent myomectomy due to intramural fibroids as part of fertility enhancement treatment at a single academic tertiary-care medical centre between the years 2011 and 2015. Demographic characteristics, pre-operative evaluation, surgical factors and post-surgical factors were compared between women who successfully conceived and those who did not following myomectomy. RESULTS: The overall clinical pregnancy rate following myomectomy was 58.3% (n = 74). Women with successful conception were significantly younger (35.4 ± 4.5 years versus 37.2 ± 4.0 years; P = 0.022), and mostly white (63.5% versus 24.3% African-American; P = 0.008). In addition, patients who conceived had larger fibroids demonstrated in pre-operative imaging and during surgery (7.3 versus 6.1 cm and 7.8 versus 6.6 cm; P = 0.003 and 0.022, respectively), with fewer cases of cavity entry determined during surgery (9.5% versus 28.3%; P = 0.005). Multivariable modified Poisson regression models identified the patient's age (risk ratio [RR] 0.96, 95% confidence interval [CI] 0.93-0.99; P =0.014) and race (RR for African-American women versus white women 0.58, 95% CI 0.38-0.88; P = 0.011) as factors significantly associated with the probability of conceiving following myomectomy. CONCLUSION(S): Age and race play a significant role in the reproductive outcomes of infertile women undergoing intramural fibroid myomectomy as part of fertility enhancement treatment. Further large prospective studies are needed to identify specific factors associated with achieving pregnancy, which will help to determine the clinical management of infertile women with intramural fibroids.

MicroRNA 21a-5p overexpression impacts mediators of extracellular matrix formation in uterine leiomyoma.

BACKGROUND: MicroRNAs (MiR) may promote fibroid development via altered expression of genes involved in cell proliferation and ECM formation, and evidence supports aberrant expression of MicroRNA (MiR) 21a-5p in fibroids. The purpose of this study was to investigate the functional significance of MiR 21a-5p overexpression in the pathobiology of leiomyomata (fibroids). METHODS: A basic science experimental design using immortalized fibroid and myometrial cell lines derived from patient-matched specimens was used. Stable overexpression of MiR-21a-5p in an immortalized fibroid and patient matched myometrial cell line was achieved through lentiviral vector infection. Main outcome measures were MiR-21-5p overexpression, target gene and protein expression, collagen (COL1A1) production, cell proliferation, cell migration, and cell cycle stages of fibroid and myometrial immortalized cell lines. RESULTS: MiR-21a-5p was overexpressed to similar levels in fibroid and myometrial cell lines after lentiviral infection. Increased expression of miR-21 resulted in increased gene and protein expression of TGF-ß3 in both fibroid and myometrial cells. Changes in expression of the ECM genes Fibronectin, Collagen 1A1, CTGF, Versican and DPT were seen in both fibroid and myometrial cells. Changes were also seen in Matrix Metalloproteinase (MMP) related genes including MMP 2, MMP 9, MMP 11 and Serpine 1 in both fibroid and myometrial cells. MiR-21 upregulation resulted in increased proliferation and migration in fibroid cells compared to myometrial cells. CONCLUSIONS: MiR-21a-5p overexpression results in changes in the expression of ECM mediators in both fibroid and myometrial cells, and increased cell proliferation in fibroid cells. These finding suggest a potential functional role of MiR-21a-5p in the development of uterine fibroids and warrant further investigation.

Comparison of sonohysterography to hysterosalpingogram for tubal patency assessment in a multicenter fertility treatment trial among women with polycystic ovary syndrome.

PURPOSE: To compare saline infusion sonohysterography (SIS) versus hysterosalpingogram (HSG) for confirmation of tubal patency. METHODS: Secondary analysis of a randomized controlled trial, Pregnancy in Polycystic Ovary Syndrome II (PPCOS II). Seven hundred fifty infertile women (18-40 years old) with polycystic ovary syndrome (PCOS) were randomized to up to 5 cycles of letrozole or clomiphene citrate. Prior to enrollment, tubal patency was determined by HSG, the presence of free fluid in the pelvis on SIS, laparoscopy, or recent intrauterine pregnancy. Logistic regression was conducted in patients who ovulated with clinical pregnancy as the outcome and HSG or SIS as the key independent variable. RESULTS: Among women who ovulated, 414 (66.9%) had tubal patency confirmed by SIS and 187 (30.2%) had at least one tube patent on HSG. Multivariable analysis indicated that choice of HSG versus SIS did not have a significant relationship on likelihood of clinical pregnancy, after adjustment for treatment arm, BMI, duration of infertility, smoking, and education (OR 1.14, 95% CI 0.77, 1.67, P = 0.52). Ectopic pregnancy occurred more often in women who had tubal patency confirmed by HSG compared to SIS (2.8% versus 0.6%, P = 0.02). CONCLUSIONS: In this large cohort of women with PCOS, there was no significant difference in clinical pregnancy rate between women who had tubal patency confirmed by HSG versus SIS. SIS is an acceptable imaging modality for assessment of tubal patency in this population.

MicroRNA-15b regulates reversion-inducing cysteine-rich protein with Kazal motifs (RECK) expression in human uterine leiomyoma.

BACKGROUND: Human uterine leiomyoma (fibroids; LYO) are the most common benign neoplasms in reproductive-aged women. Dysregulated extracellular matrix and irregular LYO reversion-inducing cysteine-rich protein with Kazal motifs (RECK) expression are thought to be mediated by aberrant microRNA (miR) expression. The relationship of miR-15b and RECK expression in LYO has not been studied. METHODS: The expression levels of miR-15b and RECK were determined by quantitative RT-PCR, Western blot, and immunohistochemistry in cultures derived from commercial primary leiomyoma (cpLYO) and myometrial (cpMYO) cell lines and leiomyoma (pLYO) and myometrium (pMYO) tissue from surgical samples respectively. The relationship between miR-15b and RECK expression in cpLYO and pLYO (compared to their respective myometrial controls) was evaluated following transfection of cell cultures with either miR-15b mimic or inhibitor. RESULTS: Elevated levels of miR-15b were observed in cpLYO (2.82-fold; p = 0.04) and pLYO cell (1.30-fold; p = 0.0001) cultures respectively compared to corresponding MYO cell controls. Following transfection with miR-15b mimic, cpLYO cells (0.62-fold; p < 0.0001) and pLYO cells (0.68-fold; p < 0.0001) demonstrated reduced RECK protein expression. Following transfection with miR-15b inhibitor, cpLYO cells (1.20-fold; p < 0.0001) and pLYO cells (1.31-fold; p = 0.0007) demonstrated elevated RECK protein expression. RECK protein expression was reduced in pLYO tissues (0.73-fold; p < 0.0001) and pLYO (0.47-fold; p = 0.047) cells when compared to the corresponding MYO tissue controls. CONCLUSION: Our findings suggest that miR-15b negatively regulates RECK expression in LYO, and increased miR-15b and decreased RECK expression may contribute to the pathobiology of LYO. The functional significance of miR-15b and RECK expression warrants further investigation as potential therapeutic targets for the treatment of human LYO.

Clinical Characteristics Associated with Antibiotic Treatment Failure for Tuboovarian Abscesses.

OBJECTIVE: Although parenteral antibiotic treatment is a standard approach for tuboovarian abscesses, a significant proportion of patients fail therapy and require interventional radiology (IR) guided drainage. The objective of this study is to assess if specific clinical factors are associated with antibiotic treatment failure. STUDY DESIGN: Retrospective medical record review of patients hospitalized for tuboovarian abscesses from 2001 through 2012 was performed. Clinical characteristics were compared for patients who underwent successful parenteral antibiotic treatment, failed antibiotic treatment necessitating subsequent IR drainage, initial drainage with concurrent antibiotics, and surgery. RESULTS: One hundred thirteen patients admitted for inpatient treatment were identified. Sixty-one (54%) patients were treated with antibiotics alone. Within this group, 24.6% failed antibiotic treatment and required drainage. Mean white blood cell count (K/µL) (18.7 ± 5.94 versus 13.9 ± 5.12) (p = 0.003), mean maximum diameter of tuboovarian abscess (cm) (6.8 ± 2.9 versus 5.2 ± 2.0) (p = 0.03), and length of stay (days) (9.47 ± 7.43 versus 4.59 ± 2.4) (p = 0.002) were significantly greater for patients who failed antibiotic treatment. CONCLUSIONS: Admission white blood cell count greater than 16 K/µL and abscess size greater than 5.18 cm are associated with antibiotic treatment failure. These factors may provide guidance for initial selection of IR guided drainage.

Donor TSH level is associated with clinical pregnancy among oocyte donation cycles.

PURPOSE: The purpose of the study is to evaluate the association between donor TSH level (independent of recipient TSH level) and recipient pregnancy outcome among fresh donor oocyte IVF cycles. METHODS: This is a retrospective cohort study investigating 232 consecutive fresh donor-recipient cycles (200 total oocyte donors) at an academic medical center. Main outcome measures include clinical pregnancy and live birth. RESULTS: Cycles were categorized into two groups based on donor TSH level (< 2.5 and ≥ 2.5 mIU/L). After controlling for multiple donor and recipient characteristics, the probability of clinical pregnancy was significantly lower among donors with TSH levels ≥2.5 mIU/L compared to those with TSH values <2.5 mIU/L (43.1 %, 95 % CI 28.5-58.9, versus 66.7 %, 95 % CI 58.6-73.9, respectively, p = 0.01). The difference in live birth rates between the two groups did not achieve statistical significance (43.1 %, 95 % CI 28.8-58.6, versus 58.0 %, 95 % CI 50.0-65.6, respectively, p = 0.09). CONCLUSIONS: Donor TSH level, independent of recipient TSH level, is associated with recipient clinical pregnancy. These findings suggest that thyroid function may impact the likelihood of pregnancy at the level of the oocyte.

Hyperplasia and fibrosis in mice with conditional loss of the TSC2 tumor suppressor in Müllerian duct mesenchyme-derived myometria.

Uterine leiomyomata are the most common tumors found in the female reproductive tract. Despite the high prevalence and associated morbidities of these benign tumors, little is known about the molecular basis of uterine leiomyoma development and progression. Loss of the Tuberous Sclerosis 2 (TSC2) tumor suppressor has been proposed as a mechanism important for the etiology of uterine leiomyomata based on the Eker rat model. However, conflicting evidence showing increased TSC2 expression has been reported in human uterine leiomyomata, suggesting that TSC2 might not be involved in the pathogenesis of this disorder. We have produced mice with conditional deletion of the Tsc2 gene in the myometria to determine whether loss of TSC2 leads to leiomyoma development in murine uteri. Myometrial hyperplasia and increased collagen deposition was observed in Tsc2(cKO) mice compared with control mice, but no leiomyomata were detected by post-natal week 24. Increased signaling activity of mammalian target of rapamycin complex 1, which is normally repressed by TSC2, was also detected in the myometria of Tsc2(cKO) mice. Treatment of the mutant mice with rapamycin significantly inhibited myometrial expansion, but treatment with the progesterone receptor modulator, mifepristone, did not. The ovaries of the Tsc2(cKO) mice appeared normal, but half the mice were infertile and most of the other half became infertile after a single litter, which was likely due to oviductal blockage. Our study shows that although TSC2 loss alone does not lead to leiomyoma development, it does lead to myometrial hyperplasia and fibrosis.

The impact of vitrification on murine germinal vesicle oocyte In vitro maturation and aurora kinase A protein expression.

PURPOSE: Investigate the effect of vitrification on in vitro maturation (IVM) and expression of Aurora kinases A, B, and C in germinal vesicle (GV)-stage oocytes. METHODS: GV-stage oocytes from B6D2F1 female mice 7-11 weeks of age were vitrified after collection, thawed, and matured in vitro for 0, 4, 8, and 12 h (hrs). The rate of germinal vesicle breakdown (GVBD), spindle apparatus assembly, and Aurora kinase mRNA and protein expression during IVM was measured. RESULTS: Oocyte vitrification was associated with significant delays in both GVBD and normal spindle apparatus assembly at 4 and 8 h of IVM (p < 0.05). There was no difference in mRNA levels between control and vitrified oocytes for any of the Aurora kinases. Aurora A protein levels were reduced in vitrified compared to control oocytes at 0 h (p = 0.008), and there was no difference at 4 and 8 h (p = 0.08 and 0.69, respectively) of IVM. CONCLUSIONS: Vitrified oocytes have delayed GVBD and normal spindle assembly during in vitro maturation. Reduced levels of Aurora A protein immediately post-thaw may be associated with the impaired oocyte maturation manifested by the delayed progression through meiosis I and II, and the atypical timing of the formation of meiotic spindles in vitrified GV-stage oocytes.

The impact of supraphysiologic serum estradiol levels on peri-implantation embryo development and early pregnancy outcome following in vitro fertilization cycles.

PURPOSE: To determine the impact of elevated serum estradiol levels (EE2-defined as levels > 90th percentile) on the day of hCG administration during IVF on oocyte fertilization, embryo development, implantation, clinical pregnancy and miscarriage rates. METHODS: A total of 2,995 consecutive IVF cycles in 1,889 patients with non-donor oocyte retrieval resulting in fresh embryo transfer between 1/1/2005 and 12/31/2011 were analyzed. Cycles were stratified by serum E2 level on the day of hCG administration into those with levels >90th percentile and ≤ 90th percentile. Rates of normal fertilization, embryo development, positive pregnancy test, implantation, clinical pregnancy and spontaneous miscarriage were compared. RESULTS: Serum estradiol above the 90th percentile on the day of hCG administration was associated with a significantly lower rate of normal fertilization (68.6 ± 20 vs. 71.6 ± 21, p = 0.02) when compared with patients with a lower serum estradiol threshold. The proportion of embryos that progressed from 2PN to 6-8 cell on day 3 was not different between the two groups. Although rates of positive pregnancy test (55.2 % vs. 57 %), implantation (26.4 % vs. 28.5 %) and clinical pregnancy (45.5 % vs. 49.4 %) were lower in patients with a higher estradiol threshold, these differences were not statistically significant. Similarly, there was no difference in the spontaneous miscarriage rates between the two groups (8.4 % vs. 7.1 %). CONCLUSIONS: Serum estradiol levels above the 90th percentile on the day of hCG administration is associated with lower oocyte fertilization rate; however, such levels do not impact embryo development, implantation, clinical pregnancy or spontaneous miscarriage rates.

Uterine fibroids and subfertility: an update on the role of myomectomy.

PURPOSE OF REVIEW: Uterine fibroids, the most common neoplasm of reproductive-aged women, can have a significant impact on quality of life, and may affect fertility and pregnancy outcomes. Although it is generally accepted that submucosal fibroids are of clinical significance, the effect of intramural and subserosal fibroids, and the benefit of surgical removal remains an area of active debate. Because of this controversy, this article will review current evidence for an association of fibroids and subfertility, and assess the impact of surgical management on fertility outcomes. RECENT FINDINGS: Recent analyses of patients with intramural fibroids have reported an increase in pregnancy loss and reduction in pregnancy and live birth rates. However, when analyzing studies with high quality diagnostic methods for assessing the endometrial cavity, no significant impact on reproductive outcomes was observed, and no benefit of myomectomy was consistently demonstrated. Myomectomy for submucosal fibroids greater than 2 cm and for intramural fibroids distorting the endometrial contour likely confers improvement of fertility outcome. SUMMARY: Submucosal fibroid location and distortion of the endometrial cavity (either submucosal or deeply infiltrating intramural fibroids) are most predictive of impaired fertility and probable benefit of surgical removal, and warrant consideration of myomectomy in the subfertile patient.

Virtual Compared With In-Clinic Transvaginal Ultrasonography for Ovarian Reserve Assessment.

OBJECTIVE: To evaluate noninferiority of virtual transvaginal ultrasonography compared with in-clinic ultrasonography for ovarian reserve assessment. METHODS: We conducted a single-site, head-to-head crossover trial. Participants performed self-administered virtual transvaginal ultrasonography at home, guided by a remote-certified ultrasound technologist, then underwent transvaginal ultrasonography in-clinic with another ultrasound technologist. Participants were women in the greater Boston area interested in evaluating ovarian reserve and recruited through social media, health care referrals, and professional networks. The uterus and ovaries were captured in sagittal and transverse views. These randomized recordings were reviewed by two or three independent, blinded reproductive endocrinologists. The primary outcome was noninferiority of the rate of clinical quality imaging produced at home compared with in clinic. Sample size was selected for greater than 90% power, given the 18% noninferiority margin. Secondary outcomes included antral follicle count equivalency and net promoter score superiority. RESULTS: Fifty-six women were enrolled from December 2020 to May 2021. Participants varied in age (19-35 years), BMI (19.5-33.9), and occupation. Ninety-six percent of virtual and 98% of in-clinic images met "clinical quality." The difference of -2.4% (97.5% CI lower bound -5.5%) was within the noninferiority margin (18%). Antral follicle counts were equivalent across settings, with a difference in follicles (0.23, 95% CI -0.36 to 0.82) within the equivalence margin (2.65). Virtual examinations had superior net promoter scores (58.1 points, 97.5% CI of difference 37.3-79.0, P<.01), indicating greater satisfaction with the virtual experience. CONCLUSION: Virtual transvaginal ultrasonography remotely guided by an ultrasonography technologist is noninferior to in-clinic transvaginal ultrasonography for producing clinical quality images and is equivalent for estimating antral follicle count. Virtual transvaginal ultrasonography had superior patient satisfaction and has potential to significantly expand patient access to fertility care. FUNDING SOURCE: This study was sponsored by Turtle Health. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04687189.

Preconception ovarian reserve and placenta-mediated pregnancy complications among infertile women.

RESEARCH QUESTION: Are preconception ovarian reserve markers, such as Anti-Mullerian hormone and antral follicle count, associated with preeclampsia and placenta mediated pregnancy complications among women with unexplained infertility who conceive with superovulation? DESIGN: This is a secondary analysis of women with unexplained infertility who had a singleton live birth after enrollment in the Analysis of Multiple Intrauterine Gestations after Ovarian Stimulation (AMIGOS) trial that randomized couples to superovulation with letrozole, clomiphene, or gonadotropins with insemination for up to 4 cycles. RESULTS: Compared to controls (N = 156), women who developed preeclampsia (N = 17) had lower Anti-Mullerian hormone levels (2.24 ± 1.20 vs. 2.89 ± 2.32, p = 0.07) and lower antral follicle count (18 ± 7.67 vs. 21 ± 11.43, p = 0.16); though these differences were not statistically significant. There was no relationship between Anti-Mullerian hormone (OR: 1.00, 95% CI: 0.76-1.25) or antral follicle count (OR: 0.98, 95% CI 0.93-1.04) with preeclampsia and between Anti-Mullerian hormone (OR: 1.00, 95% CI: 0.83-1.17) and antral follicle count (OR: 1.00, 95% CI: 0.97-1.04) with placenta medicated pregnancy complications after adjusting for age, BMI and race. CONCLUSIONS: Preconception ovarian reserve markers are not associated with preeclampsia and placenta mediated pregnancy complications among women with unexplained infertility who conceive with superovulation with insemination.

Embryo cryopreservation and utilization in the United States from 2004-2013.

OBJECTIVE: To evaluate the quantity and use of embryos cryopreserved at assisted reproductive technology (ART) clinics in the United States from 2004 through 2013 and to characterize trends in ART cycles in which all embryos were cryopreserved. DESIGN: Retrospective analysis. SETTING: Not applicable. PATIENTS: Registry data from the Society for Assisted Reproductive Technology. INTERVENTIONS: Historical cohort of U.S. ART cycles reported to the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System between 2004 and 2013. MAIN OUTCOME MEASURES: Number of embryos cryopreserved and factors associated with having cryopreserved embryos. RESULTS: The percentage of fresh cycles in which all embryos were frozen increased dramatically each year after 2010: 15.6% (2010), 19.9% (2011), 30.7% (2012), and 40.7% (2013). During 10 years, 1,954,548 embryos were cryopreserved and 717,345 embryos were transferred. In freeze-only cycles from 2004 to 2013, there was a significant increase in the percentage of women with diminished ovarian reserve (19.9% to 34.1%) and in those who used preimplantation genetic testing (3.2% to 6.9%). During the 10-year period, there were 294,575 fresh cycles with embryo transfer and at least one embryo cryopreserved. Overall, 52.5% (n = 154,543) did not undergo a subsequent frozen embryo transfer, 29.5% (n = 40,462) were left with no frozen embryos, 50.4% (n = 68,875) had one-five embryos, and 20.0% (n = 27,396) had ≥six. Factors associated with having excess embryos included donor oocyte cycles and increased antimüllerian hormone levels. CONCLUSIONS: There has been a sharp increase in U.S. ART cycles in which all embryos are frozen and this may result in more embryos in storage.

Economic implications of insurance coverage for in vitro fertilization in the United States. A review.

OBJECTIVE: To analyze cost-effectiveness studies in regard to the costs of in vitro fertilization (IVF) and discuss specific economic trends that may affect the future utilization of IVF in the United States. STUDY DESIGN: Health economics. A Pub Med literature review and the Centers for Disease Control's (CDC) Fertility Clinic Success Rate registry served to access cost analyses and trends, respectively. RESULTS: The average cost of an IVF cycle in the U.S. is $9,226. Among policies that provide IVF services, the increase in premium per month ranges from $0.67 to $14. CONCLUSION: When IVF is provided as a health benefit, the cost increases can be variable. As utilization increases, contemporary cost analyses and outcomes research will aid providers, third-party payers and policymakers in better understanding the economic impact of lVF.

Ablation of leptin signaling disrupts the establishment, development, and maintenance of endometriosis-like lesions in a murine model.

Leptin, a 16-kDa cytokine, has been implicated in several reproductive processes and disorders. Notably, elevated leptin levels in the peritoneal fluid of women with mild endometriosis has been demonstrated, suggesting a role for this cytokine in the early stages of disease establishment. To gain insight into the functional significance of leptin during the initial requisite proliferative and neovascularization events involved in endometriosis, we investigated the effect of disruption of in vivo leptin signaling on the establishment and/or maintenance of an endometriosis-like lesion in a syngeneic immunocompetent mouse model of endometriosis. Findings of this study show that the disruption of leptin signaling by ip injection of the pegylated leptin peptide receptor antagonist (LPrA) impairs the establishment of endometriosis-like lesions (derived from uteri of C57BL/6 female siblings) and results in a reduction of viable organized glandular epithelium, vascular endothelial growth factor-A expression, and mitotic activity. LPrA treatment resulted in a significant reduction of microvascular density in endometriosis-like lesions after continuous and acute courses. Endometriosis-like lesions (derived from tissue with functional leptin receptor) of Lepr(db) hosts (nonfunctional leptin receptor) were phenotypically similar to those of LPrA-treated mice. Our results confirm that leptin signaling is a necessary component in lesion proliferation, early vascular recruitment, and maintenance of neoangiogenesis in a murine model of endometriosis.