High estradiol levels in fresh embryo transfer cycles are not associated with detrimental impact on birth outcomes.

PURPOSE: There is an unclear relationship between estradiol levels and fresh embryo transfer (ET) outcomes. We determined the relationship between estradiol on the day of trigger, in fresh ET cycles without premature progesterone elevation, and good birth outcomes (GBO). METHODS: We identified autologous fresh ET cycles from 2015 to 2021 at multiple clinics in the USA. Patients with recurrent pregnancy loss, uterine factor, and elevated progesterone on the day of trigger (progesterone > 2 ng/mL or 3-day area under the curve > 4.5 ng/mL) were excluded. The primary outcome was GBO (singleton, term, live birth with appropriate weight). Log-binomial generalized estimating equations determined the likelihood of outcomes. RESULTS: Of 17,608 fresh ET cycles, 5025 (29%) yielded GBO. Cycles with estradiol ≥ 4000 pg/mL had a greater likelihood of GBO compared to cycles < 1000 pg/mL (aRR = 1.32, 95% CI 1.13-1.54). Pairwise comparisons of estradiol between < 1000 pg/mL versus 1000-1999 pg/mL and 1000-1999 pg/mL versus 2000-2999 pg/mL revealed a higher likelihood of GBO with higher estradiol (aRR 0.83, 95% CI 0.73-0.95; aRR 0.91, 95% CI 0.85-0.97, respectively). Comparisons amongst more elevated estradiol levels revealed that the likelihood of GBO remained similar between groups (2000-2999 pg/mL versus 3000-3999 pg/mL, aRR 1.04, 95% CI 0.97-1.11; 3000-3999 pg/mL versus ≥ 4000 pg/mL, aRR 0.96, 95% CI 0.9-1.04). CONCLUSION: In fresh ET cycles, higher estradiol levels were associated with an increased prevalence of GBO until estradiol 2000-2999 pg/mL, thereafter plateauing. In fresh ET candidates, elevated estradiol levels should not preclude eligibility though premature progesterone rise, and risk of ovarian hyperstimulation syndrome must still be considered.

A View from the past into our collective future: the oncofertility consortium vision statement.

PURPOSE: Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. METHODS: The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. RESULTS: This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. CONCLUSION: The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future.

Loss of anti-Müllerian hormone (AMH) immunoactivity due to a homozygous AMH gene variant rs10417628 in a woman with classical polycystic ovary syndrome (PCOS).

Anti-Müllerian hormone (AMH) is produced by granulosa cells of pre-antral and small antral ovarian follicles. In polycystic ovary syndrome (PCOS), higher levels of serum AMH are usually encountered due to the ample presence of small antral follicles and a high AMH production per follicular unit which have led to the proposal of AMH as a serum diagnostic marker for PCOS or as a surrogate for polycystic ovarian morphology (PCOM). However, heterozygous coding mutations of the AMH gene with decreased in vitro bioactivity have been described in some women with PCOS. Such mutation carriers have a trend toward reduced serum AMH levels compared to noncarriers, although both types of women with PCOS have similar circulating gonadotropin and testosterone (T) levels. This report describes a normal-weight woman with PCOS by NIH criteria with severely reduced AMH levels (index woman with PCOS). Our objective was to examine the molecular basis for her reduced serum AMH levels and to compare her endocrine characteristics to similar-weight women with PCOS and detectable AMH levels. Twenty normoandrogenic ovulatory (control) and 13 age- and BMI-matched women with PCOS (19-35 years; 19-25 kg/m2) underwent transvaginal sonography and serum hormone measures including gonadotropins, sex hormone-binding globulin, total and free T, androstenedione, dehydroepiandrosterone sulfate, estrone, estradiol and AMH. The latter was measured by ELISA (Pico-AMH: Ansh Labs, Webster, TX, USA). Women with PCOS and detectable AMH had higher serum AMH (10.82 (6.74-13.40) ng/ml, median (interquartile range)), total and free T (total T: 55.5 (49.5-62.5) ng/dl; free T: 5.65 (4.75-6.6) pg/ml) levels and greater total antral follicle count (AFC) (46 (39-59) follicles) than controls (AMH: 4.03 (2.47-6.11) ng/ml; total T: 30 (24.5-34.5) ng/dl; free T: 2.2 (1.8-2.45) pg/ml; AFC 16 (14.5-21.5) follicles, P < 0.05, all values), along with a trend toward LH hypersecretion (P = 0.06). The index woman with PCOS had severely reduced serum AMH levels (∼0.1 ng/ml), although she also had a typical NIH-defined PCOS phenotype resembling that of the other women with PCOS and elevated AMH levels. All women with PCOS, including the index woman with PCOS, exhibited LH hypersecretion, hyperandrogenism, reduced serum estrogen/androgen ratios and PCOM. A homozygous Ala515Val variant (rs10417628) in the mature region of AMH was identified in the index woman with PCOS. Recombinant hAMH-515Val displayed normal processing and bioactivity, yet had severely reduced immunoactivity when measured by the commercial pico-AMH ELISA assay by Ansh Labs. In conclusion, homozygous AMH variant rs10417628 may severely impair serum AMH immunoactivity without affecting its bioactivity or PCOS phenotypic expression. Variants in AMH can interfere with serum AMH immunoactivity without affecting the phenotype in PCOS. This observation can be accompanied by discordance between AMH immunoactivity and bioactivity.

Mechanisms of intergenerational transmission of polycystic ovary syndrome.

Developmental origins of adult disease (DoHAD) refers to critical gestational ages during human fetal development and beyond when the endocrine metabolic status of the mother can permanently program the physiology and/or morphology of the fetus, modifying its susceptibility to disease after birth. The aim of this review is to address how DoHAD plays an important role in the phenotypic expression of polycystic ovary syndrome (PCOS), the most common endocrinopathy of women characterized by hyperandrogenism, oligo-anovulation and polycystic ovarian morphology. Clinical studies of PCOS women are integrated with findings from relevant animal models to show how intergenerational transmission of these central components of PCOS are programmed through an altered maternal endocrine-metabolic environment that adversely affects the female fetus and long-term offspring health. Prenatal testosterone treatment in monkeys and sheep have been particularly crucial in our understanding of developmental programming of PCOS because organ system differentiation in these species, as in humans, occurs during fetal life. These animal models, along with altricial rodents, produce permanent PCOS-like phenotypes variably characterized by LH hypersecretion from reduced steroid-negative feedback, hyperandrogenism, ovulatory dysfunction, increased adiposity, impaired glucose-insulin homeostasis and other metabolic abnormalities. The review concludes that DoHAD underlies the phenotypic expression of PCOS through an altered maternal endocrine-metabolic environment that can induce epigenetic modifications of fetal genetic susceptibility to PCOS after birth. It calls for improved maternal endocrine-metabolic health of PCOS women to lower their risks of pregnancy-related complications and to potentially reduce intergenerational susceptibility to PCOS and its metabolic derangements in offspring.

Measures of Patient Dissatisfaction With Health Care in Polycystic Ovary Syndrome: Retrospective Analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder in women; however, many clinicians may not be well versed in scientific advances that aid understanding of the associated reproductive, metabolic, and psychological abnormalities. Women with PCOS are dissatisfied with health care providers, the diagnostic process, and the initial treatment of PCOS and seek information through alternative sources. This has affected the patient-physician relationship by allowing medical information acquired through the internet, whether correct or not, to become accessible to patients and reshape their health care perspective. Patient dissatisfaction with health care providers regarding PCOS raises questions about the responsibilities of academic institutions to adequately train and maintain the competence of clinicians and government agencies to sufficiently support scientific investigation in this field. OBJECTIVE: The primary aim was to examine internet searching behaviors of the public regarding PCOS vs another highly prevalent gynecologic disorder. The secondary aim was to explore satisfaction with health care among patients with PCOS and their internet use. The tertiary aim was to examine medical education in reproductive endocrinology and infertility (REI) during obstetrics and gynecology (Ob/Gyn) residency as a proxy for physician knowledge in this field. METHODS: Google search trends and StoryBase quantified monthly Google absolute search volumes for search terms related to PCOS and fibroids (January 2004 to December 2017; United States). The reproductive disorder, fibroids, was selected as a comparison group because of its high prevalence among women. Between female groups, monthly absolute search volumes and their trends were compared. A Web-based questionnaire (June 2015 to March 2018) explored health care experiences and the internet use of women with PCOS. REI rotation information during Ob/Gyn residency in the United States was obtained from the Association of Professors of Gynecology and Obstetrics website. RESULTS: For PCOS (R=0.89; P<.01), but not fibroids (R=0.09; P=.25), monthly absolute search volumes increased significantly. PCOS-related monthly absolute search volumes (mean 384,423 searches, SD 88,756) were significantly greater than fibroid-related monthly absolute search volumes (mean 348,502 searches, SD 37,317; P<.05). PCOS was diagnosed by an Ob/Gyn in 60.9% (462/759) of patients, and 57.3% (435/759) of patients were dissatisfied with overall care. Among patients with PCOS, 98.2% (716/729) searched for PCOS on the Web but only 18.8% (143/729) of patients joined an online PCOS support group or forum. On average, Ob/Gyn residencies dedicated only 4% (2/43) of total block time to REI, whereas 5.5% (11/200) of such residencies did not offer any REI rotations. CONCLUSIONS: Over time, PCOS has been increasingly searched on the Web compared with another highly prevalent gynecologic disorder. Patients with PCOS are dissatisfied with their health care providers, who would benefit from an improved understanding of PCOS during Ob/Gyn residency training.

Euploid rates among oocyte donors: is there an optimal age for donation?

PURPOSE: To examine cycle blastocyst euploid rates among age subgroups of oocyte donors. METHODS: Retrospective cohort analysis of ova donation in vitro fertilization cycles (OD-IVF) for which trophectoderm biopsy for preimplantation genetic testing for aneuploidy (PGT-A) by array comparative genomic hybridization (aCGH) or next generation gene sequencing (NGS) was employed between January 2015 and December 2018 in a single high-volume fertility center. RESULTS: Compared to oocyte donors age 26-30, oocyte donors age ≤ 25 had similar cycle blastocyst euploid rates (80 [66.7, 87.5]%, vs. 75 [62.5, 87.5]%, median [IQR], p = 0.07), blastocyst formation rates (66.7 [50, 75]%, vs. 62.5 [52, 75]%, p = 0.55), and number of retrieved oocytes (29 [23, 37] vs. 27 [20, 35], p = 0.18). Age of oocyte donor from 18 to 34 was not correlated with cycle blastocyst euploid rate. CONCLUSION: Oocyte donors age ≤ 25 had similar cycle blastocyst euploid rates, blastocyst formation rates, and number of retrieved oocytes compared to donors age 26-30. There was no correlation between cycle blastocyst euploid rates and age of the oocyte donor from 18 to 34 years. Given the lack of significant age-related change in cycle blastocyst euploid rates, our data support existing practices which do not favor a specific age subgroup of young oocyte donors.

Endometriosis and Imaging.

Endometriosis is a condition with variable location, size, and lesion composition which poses a diagnostic imaging challenge for the practicing gynecologist. Transvaginal ultrasound and magnetic resonance imaging are the most frequent imaging techniques used for its evaluation, but transvaginal ultrasound should be the first-line approach, as it is often sufficient, followed by modified ultrasound techniques. Magnetic resonance imaging should be considered when a diagnosis has not been achieved by sonographic means or when the renal system needs to be concurrently evaluated. Computed tomography has no role in the routine evaluation of endometriosis except in very few particular scenarios.

Imaging in Endometriosis and Adenomyosis.

Endometriosis and adenomyosis may be accurately diagnosed using ultrasound (US). Several findings are characteristic and various US modalities have been described. Recent development of 3-dimensional transvaginal US has resulted in a major advance in the evaluation of adenomyosis. Endometriotic manifestations can also be accurately evaluated with US, which is and should remain the first-line approach for the evaluation of these conditions. Obvious advantages over magnetic resonance imaging include its wide-availability, tolerability, less time-consumption, more accessible price and familiarity of gynecologists with its use. This technology's full potential can be achieved using 3-dimensional imaging and/or modified techniques according to the particular clinical scenario.

Fragile X premutation in women: recognizing the health challenges beyond primary ovarian insufficiency.

Fragile X premutation carriers have 55-200 CGG repeats in the 5' untranslated region of the FMR1 gene. Women with this premutation face many physical and emotional challenges in their life. Approximately 20% of these women will develop fragile X-associated primary ovarian insufficiency (FXPOI). In addition, they suffer from increased rates of menstrual dysfunction, diminished ovarian reserve, reduction in age of menopause, infertility, dizygotic twinning, and risk of having an offspring with a premutation or full mutation. Consequent chronic hypoestrogenism may result in impaired bone health and increased cardiovascular risk. Neuropsychiatric issues include risk of developing fragile X-associated tremor/ataxia syndrome, neuropathy, musculoskeletal problems, increased prevalence of anxiety, depression, and sleep disturbances independent of the stress of raising an offspring with fragile X syndrome and higher risk of postpartum depression. Some studies have reported a higher prevalence of thyroid abnormalities and hypertension in these women. Reproductive health providers play an important role in the health supervision of women with fragile X premutation. Awareness of these risks and correlation of the various manifestations could help in early diagnosis and coordination of care and services for these women and their families. This paper reviews current evidence regarding the possible conditions that may present in women with premutation-sized repeats beyond FXPOI.

Morbid obesity and outcome of ectopic pregnancy following capped single-dose regimen methotrexate.

PURPOSE: Evaluate whether morbid obesity influenced resolution, number of doses or ultimately surgical management of tubal ectopic pregnancy (TEP) when treated with single-dose regimen methotrexate (SDR-MTX) capped at 100 mg. METHODS: Retrospective cohort study of patients with a diagnosis of TEP who underwent MTX treatment from 2000 to 2013. Patients were excluded if initial ß-hCG <1000 mIU/mL, did not have ß-hCG follow-up or were not treated with SDR-MTX. Per protocol, dose was administered at 50 mg/m2 with a capped maximum of 100 mg. Patients were divided based on their BMI (<40 and ≥40 kg/m2). Demographic variables, ß-hCG before treatment, maximum diameter of ectopic size, embryonic heart tones, decrease of ß-hCG, need for additional MTX doses and surgery despite treatment were recorded and compared among the groups. RESULTS: 151 women were included in the study, 89.4% (135/151) non-morbidly obese and 10.6% (16/151) morbidly obese. No differences in age distribution, ethnicity, pre-treatment presence of embryonic heart tones, maximum diameter of ectopic size ≥35 mm and ß-hCG ≥5000 mIU/ml were found. Following treatment, the proportion of patients with at least an 80% decrease in their ß-hCG levels or need for surgery were similar, however, morbidly obese patients were significantly more likely [11/134 vs. 5/16, OR 5.1 (1.5-17.3, p = 0.015)] to require an additional MTX dose. CONCLUSION: Among patients with TEP, morbidly obese patients were five times more likely to require an additional dose compared to non-morbidly obese when SDR-MTX capped at 100 mg was used for medical management.

Risk of neonatal mortality according to gestational age after elective repeat cesarean delivery.

PURPOSE: Despite the well-known neonatal morbidity risks after elective cesarean deliveries performed before 39 weeks, there are scarce data regarding mortality risks. The objective of this study was to calculate the risk of neonatal mortality after elective repeat cesarean delivery (ERCD) by gestational age. METHODS: The Linked Birth-Infant Death Data Files from the Vital Statistics Data of the Center for Disease Control and Prevention of the U.S. from 2004 to 2008 were analyzed. Only ERCD cases were included. Early death (<7 days), neonatal death (<28 days), and infant death (<1 year) were evaluated. A logistic regression model was used to calculate odds ratios. Cases delivered at 37-41 weeks were studied with 40 weeks as reference. RESULTS: A total of 483,052 cases were included for analysis. The distribution of rates and odds ratios for infant, neonatal and early death was U-shaped with the nadir at 39 weeks. There was a statistically significant increase in early death at 37 compared to 40 weeks' gestation [OR (95 %) CI = 1.929(1.172-3.176)]. No statistical increase was found in any of the other mortality risks. CONCLUSION: There is an increased risk in early death with ERCD performed at 37 weeks. Our study provides evidence of neonatal harm beyond the reported morbidity risks.

Optimal timing for term delivery of twin pregnancies: a population-based study.

OBJECTIVE: The objective of this study was to examine the risk of adverse neonatal outcomes after twin delivery according to gestational age. MATERIALS AND METHODS: The U.S. Natality Database from 2007 to 2010 was reviewed. Inclusion criteria were twin deliveries and gestational age of 37 to 42 weeks. Exclusion criteria were congenital anomalies and missing/incomplete data. Cases were subdivided by gestational age into early term, term, and late term. Singleton pregnancies matched by delivery time and location were selected as controls. Outcome variables included were low Apgar score, assisted ventilation, neonatal intensive care unit admission, surfactant/antibiotic use, seizures, and birth injury. Logistic regression analysis was used to calculate adjusted odds ratios according to gestational age and plurality, using singleton term as reference. RESULTS: A total of 220,169 twin and 270,540 singleton deliveries were identified. The risk of adverse neonatal outcomes for twins was higher than for singletons. For twins, the distribution of the risks of the composite of adverse neonatal outcomes was linear, being the lowest at early term and the highest at late term, whereas the distribution for singletons was u-shaped being lowest at term compared with early and late term. CONCLUSIONS: Twins are at higher risk of suboptimal neonatal outcomes than singletons, but do better when delivered at early term rather than term or late term.

Impact of time interval from cesarean delivery to frozen embryo transfer on reproductive and neonatal outcomes.

OBJECTIVE: To evaluate differences in reproductive and neonatal outcomes on the basis of the time interval from cesarean delivery to subsequent frozen embryo transfer (FET). DESIGN: Retrospective cohort. SETTING: Multicenter fertility practice. PATIENTS: Women undergoing autologous elective single embryo transfer FET after prior cesarean delivery. INTERVENTION: Time from prior cesarean delivery to subsequent FET. MAIN OUTCOME MEASURES: live birth (LB). RESULTS: A total of 6,556 autologous elective single embryo transfer FET cycles were included. Frozen embryo transfer cycles were divided into eight groups on the basis of the time interval from prior cesarean delivery to subsequent FET in months. A secondary analysis was then performed with time as a continuous variable. The proportion of LBs did not differ significantly across all time interval groups and over continuous time (range: 40.0%-45.6%). The mean gestational age at the time of delivery did not significantly differ as the time between prior cesarean delivery and subsequent FET increased (range: 37.3-38.4). When time was evaluated continuously, the proportion of preterm births was higher with a shorter time between cesarean delivery and subsequent FET. The mean birth weight ranged from 3,181-3,470g, with a statistically significant increase over time. However, the proportions of extremely low birth weight, very low birth weight, and low birth weight did not significantly differ. CONCLUSION: There were no significant differences in reproductive outcomes on the basis of the time interval from cesarean delivery to FET, including LB. The proportion of preterm deliveries decreased with a longer time between cesarean delivery and FET. Differences in mean neonatal birth weight were not clinically significant because the proportion of low birth weight neonates was not significantly different over time. Although large, this sample cannot address all outcomes associated with short interpregnancy intervals, particularly rarer outcomes such as uterine rupture. When counseling patients, the timing of FET after cesarean delivery must be balanced against the risks of increasing maternal age on reproductive and neonatal outcomes.

A local hemostatic agent for the management of postpartum hemorrhage due to placenta previa and placenta accreta: a cross-sectional study.

PURPOSE: To describe the use of a local hemostatic agent (LHA) for the management of postpartum hemorrhage (PPH) due to bleeding of the placental bed in patients taken to caesarean section at Fundación Santa Fe de Bogotá University Hospital. SAMPLE: A total of 41 pregnant women who had a caesarean section and developed PPH. METHODS: A cross-sectional study. Analysis of all cases of PPH during caesarean section presented from 2006 up to and including 2012 at Fundación Santa Fe de Bogotá University Hospital. MAIN OUTCOME MEASURE: Emergency hysterectomy due to PPH. RESULTS: The proportion of hysterectomies was 5 vs. 66 % for the group that received and did not receive management with a LHA respectively (PR 0.07, CI 95 % 0.01-0.51 p < 0.01). For the group managed without a LHA, 80 % of patients needed hemoderivatives transfusion vs. 20 % of patients in the group managed with a LHA (PR 0.24, CI 95 % 0.1-0.6 p < 0.01). A reduction in the mean days of hospitalization in addition to a descent in the proportion of patients admitted to the intensive care unit (ICU) was noticed when comparing the group that received a LHA versus the one that did not. CONCLUSION: An inverse association between the use of a LHA in patients with PPH due to bleeding of the placental bed and the need to perform an emergency obstetric hysterectomy was observed. Additionally there was a significant reduction in the mean duration of hospital stay, use of hemoderivatives and admission to the ICU.

Availability of Fertility Preservation Information on the Websites of U.S. News and World Report Top-Ranked Pediatric Cancer Programs.

Purpose: To evaluate the availability of fertility preservation (FP) services and educational resources on the websites of top-ranked U.S. pediatric cancer programs. Methods: Cross-sectional survey of information and resources related to FP on websites from top-ranked pediatric cancer programs according to the 2018-2019 U.S.-News & World Report (USNWR) ranking. Factors that predicted the website availability of FP information or a fertility team were analyzed, as was availability in Spanish and for specific groups by sex and puberty status. As a surrogate marker of comprehensive oncological services, the availability of resources for psychological support was compared to FP. Results: A fertility team was referenced on the website of 36% of programs, but only 32% provided FP educational resources for patients. Among them, 100%, 93.8%, 93.8%, and 68.8% provided specific information for postpubertal females, prepubertal females, postpubertal males, and prepubertal males, respectively. The majority (93.8%) did not provide information in Spanish. The ranking on USNWR (p < 0.05) and patient volume (p < 0.05) positively correlated with the availability of FP information and fertility team on the program's website. Information regarding psychological support was provided more often than information regarding FP (96% vs. 32%, p < 0.05). Conclusion: The majority of the top-ranked pediatric cancer programs in the United States do not list FP resources or a fertility team on their website. The lack of resources is particularly concerning for the Spanish-speaking population, as well as for prepubertal males. This may be potentially hindering access to FP and contributing to health care disparities.

Primary ovarian insufficiency in an adolescent population: clinical phenotype and diagnostic approach.

Background Primary ovarian insufficiency (POI) can be seen in adolescents secondary to genetic or autoimmune conditions, or gonadotoxic therapies. Often times, its underlying cause is not identified. It is a rare condition in pediatrics, but a thorough evaluation is required for a timely diagnosis and optimizing outcomes. Objectives We aim to describe the clinical phenotype of idiopathic POI in an adolescent population seen in a referral center, and evaluate its diagnostic approach. Methods All patients evaluated between 2012 and 2018 were identified using the diagnostic codes for POI. Medical records were manually reviewed and clinical information was extracted. Cases were excluded from the final sample if they were found to have incomplete diagnostic information, Turner syndrome, eating disorders, gonadal surgeries and/or a history of oncological conditions or treatments. Results Forty-eight patients with POI were identified, and only seven met the established criteria. Anti-ovarian and anti-thyroid antibodies were evaluated in 100% and 86%, respectively, while only 29% were tested for anti-adrenal autoimmunity. The karyotype was obtained consistently, while the fragile X mental retardation 1 (FMR1) gene expansion was only assessed in approximately a third of the patients. Finally, only 29% of patients received reproductive counseling or referral to a fertility specialist. Conclusions Diagnostic evaluation for POI appears to be challenging to pediatric providers. Anti-ovarian antibodies are frequently obtained despite the lack of their clinical significance in POI, while anti-adrenal antibodies, which are the preferred diagnostic test, are not commonly obtained. Reproductive orientation or referral is seldom provided to the adolescent population.

Outcomes in subsequent pregnancies after wedge resection for interstitial ectopic pregnancy: a retrospective cohort study.

OBJECTIVE: The objective of this study is to evaluate pregnancy outcomes in patients with a history of wedge resection for interstitial ectopic pregnancy (WRIEP). METHODS: Retrospective cohort study of pregnancies with a history of WRIEP from 2000 to 2013 at two inner city hospitals in Detroit, MI. Pregnant-matched controls (1:3) were selected and included patients with history of surgically treated tubal ectopic pregnancy and delivered patients without history of ectopic pregnancy. Pregnancy outcomes, including a composite, were compared among the groups. RESULTS: Eighty-three cases of interstitial pregnancy were identified. Sixty-three (75.9%) underwent WRIEP from which 19 (30.2%) had a subsequent pregnancy and 11 (57.9%) carried it ≥20 weeks. No difference in subsequent pregnancy outcomes including the composite was found among patients with prior WRIEP and patients with history of surgically treated tubal ectopic pregnancy except for a longer interpregnancy interval. Compared with delivered patients without a history of ectopic pregnancy, no difference in late obstetric outcomes was found including the composite, gestational age at delivery in weeks (38.2 versus 38.1, p = .955), preterm delivery rate (30% versus 21%, p = .674), and proportion of term vaginal (40% versus 52%, p = .721) or cesarean deliveries (60% versus 30%, p = .137). The most common indication for cesarean among patients with a history of WRIEP was a history of such (5/6, 83.3%) and there were no cases of abnormal placentation. CONCLUSION: Findings suggest that a history of WRIEP is not associated with increased risk of adverse pregnancy outcomes.

Risk factors for cervical ectopic pregnancy.

OBJECTIVE: To evaluate risk factors for cervical ectopic pregnancies. METHODS: Retrospective, quasi-experimental case-control study of cervical ectopic pregnancy (CEP) cases from 2000-2013. Two groups were selected as controls, patients with tubal ectopic (TEP) and intrauterine pregnancies (IUP) without a history of TEP, matched by year of pregnancy and randomly sampled in a 1:3 case-control ratio per each study group. RESULTS: 21 cases were identified and 126 controls included, 63 TEP and IUP each. A binary logistic regression model was used to analyze whether statistically significant preceding factors from a bivariate analysis could predict CEP. Compared to patients with IUP, CEP patients had a higher history of elective abortions, D&C and cervical excisional procedures, with a high effect size (>0.7). Compared to patients with TEP, CEP patients had a higher history of D&C and cervical excisional procedures, with a high effect size (>.7). The risk of CEP was significantly higher with a prior history of D&C compared to an IUP (aOR 1.4; 95% CI, 1.1-9.1; p=0.04) and a TEP (aOR 6.1; 95% CI, 1.8-21.2; p=0.04). CONCLUSION: D&C is a strong risk factor for CEP when compared to pregnancies in other locations. These findings confirm previous associations described in case series.

Adipose Insulin Resistance in Normal-Weight Women With Polycystic Ovary Syndrome.

CONTEXT: Normal-weight women with polycystic ovary syndrome (PCOS) may have adipose tissue insulin resistance (adipose-IR). OBJECTIVE: To examine whether adipose-IR and subcutaneous (SC) abdominal adipose stem cell (ASC) gene expression are altered in normal-weight women with PCOS and correlated with hyperandrogenemia and/or whole-body IR. DESIGN: Prospective cohort study. SETTING: Academic medical center. PATIENTS: Ten normal-weight women with PCOS and 18 control subjects matched for age and body mass index. INTERVENTION(S): Women underwent circulating hormone and metabolic measurements, IV glucose tolerance testing, total-body dual-energy x-ray absorptiometry, and SC abdominal fat biopsy. MAIN OUTCOME MEASURE(S): Adipose-IR (fasting insulin × total fatty acid levels) and SC abdominal ASC gene expression were compared between groups and correlated with clinical outcomes. RESULTS: Adipose-IR was greater in women with PCOS than in control subjects (P < 0.01), with 29 pmol/L × mmol/L providing 94% specificity and 80% sensitivity in discriminating the two groups (P < 0.001). Adipose-IR positively correlated with serum androgen and log of fasting triglyceride (TG) levels, percentage of small adipocytes (P < 0.01, all correlations), and acute insulin response to glucose (P < 0.05); and negatively correlated with insulin sensitivity (Si; P < 0.025) and serum adiponectin levels (P < 0.05). Adjusting for serum androgens, adipose-IR correlations with Si and log TG levels remained significant. ASC genes were differentially expressed by the two groups. Expression of functionally critical genes was associated with serum testosterone and/or fasting insulin levels. CONCLUSION: Normal-weight women with PCOS have increased adipose-IR and altered ASC gene expression related to hyperandrogenism and IR.