Socioeconomic disparities in fertility treatments and associated likelihood of livebirth following in vitro fertilization.

OBJECTIVE: To determine whether neighborhood-level socioeconomic characteristics are associated with the likelihood of livebirth (LB) following in vitro fertilization (IVF). Specifically, we evaluated neighborhood-level household income, unemployment rate, and educational attainment. DESIGN: A retrospective cross-sectional study was conducted for patients undergoing autologous IVF cycles. SETTING: Large academic health system. INTERVENTIONS: For each patient, ZIP code of residence was used as a proxy for neighborhood. Neighborhood characteristics were compared between patients with and without LB. Generalized estimating model was used to adjust the association between SES factors and likelihood of a live birth with respect to relevant clinical factors. RESULTS: A total of 4942 autologous IVF cycles from 2768 patients were included: 1717 (62.0%) had at least one associated LB. Patients who achieved LB from IVF were younger, had higher anti-Mullerian hormone (AMH) levels, lower body mass index (BMI), and differed by ethnic background, primary language, and neighborhood socioeconomic characteristics. In a multivariable model, language, age, AMH, and BMI were associated with a live birth from IVF. None of the neighborhood-level socioeconomic variables were associated with the total number of IVF cycles or cycles required to achieve first LB. CONCLUSION: Patients living in neighborhoods with lower annual household income have lower odds of livebirth after IVF compared to those living in more affluent areas, despite undergoing the same number of IVF stimulation cycles.

The evolving landscape of donor egg treatment: success, women's choice, and anonymity.

PURPOSE: To analyze donor oocyte (DE) data across 6 years for oocyte usage efficiency, trends, and whether changes impacted outcomes. METHODS: From 2014 to 2019, 323 DE embryo transfers were completed in 200 recipients using oocytes derived of 163 donors. We assessed data for oocytes being freshly retrieved (FRESH-EGG) vs. purchased frozen (FROZEN-EGG); embryos transferred fresh (FRESH-ET) vs. frozen (FROZEN-ET); cycles SHARED (two recipients) vs. SOLE (one recipient); single (SET) vs. double (DET) embryo transfers and usage of PGT-A. Primary outcome was ongoing pregnancy plus live birth (OP/LB) rate. RESULTS: A total of 229 FRESH-EGG (70%) and 94 FROZEN-EGG (30%) cycles were completed. Overall, the use of FRESH-EGG yielded a higher OP/LB compared to FROZEN-EGG (49% vs. 30%, p = 0.001); within the FRESH-EGG group, OP/LB was similar when comparing FRESH-ET vs. FROZEN-ET (58% vs. 45%, p = 0.07). Within the FRESH-ET group, those using FRESH-EGG had a higher OP/LB than those using FROZEN-EGG (58% vs. 27%, p < 0.001). SHARED vs. SOLE cycles (p = 0.6), donor age (21-32 years; p = 0.4), and age of intended parents (maternal p = 0.3, paternal p = 0.2) did not significantly impact OP/LB. Notably, the use of PGT-A did not improve odds for an OP/LB (p = 0.7). CONCLUSION: The use of FRESH-EGG with FRESH-ET without PGT-A remains superior to newer DE treatment combinations. Specifically, the use of FROZEN-EGG and PGT-A did not improve outcomes. Although changing DE practices may enhance experience and affordability, patients and providers must appreciate that choices do not always favorably impact success. Additionally, newly available genetic-ancestry testing may pose longer-term ramifications mandating change in treatment and/or counseling.

In vivo oocyte retrieval in a young woman with ovarian cancer.

BACKGROUND: Oocyte cryopreservation is rapidly becoming an option for single women recently diagnosed with cancer who wish to preserve their fertility. We describe oocyte retrieval in young women with invasive ovarian cancer. CASE: A 23-year-old nulliparous woman had recurrence of a mixed ovarian germ cell tumor after unilateral oophorectomy. Concern of involvement of her remaining ovary and need for postoperative chemotherapy prompted decision to perform controlled ovarian hyperstimulation followed by intraoperative in vivo oocyte retrieval. CONCLUSION: Oocyte cryopreservation through controlled ovarian hyperstimulation leading up to oocyte retrieval at the time of surgical staging for gynecologic malignancies can be coordinated in a timely fashion, affording fertility preservation without significant treatment delay. Greater awareness of this capability may prompt extension of oocyte cryopreservation services to all potential candidates and help mobilize the establishment of referral pathways and multidisciplinary teams of general gynecologists, gynecologic oncologists, and reproductive endocrinologists.

Polycystic ovarian syndrome: role of imaging in diagnosis.

Polycystic ovarian syndrome (PCOS) is the most common endocrine abnormality in women of reproductive age and carries with it significant health risks, including infertility, endometrial hyperplasia, diabetes, and cardiovascular disease. The workup of PCOS has evolved to include the use of pelvic ultrasonography (US). Ovarian imaging is crucial in the evaluation of patients with suspected PCOS. Although findings of polycystic ovaries are commonly seen at routine US and are frequently not associated with PCOS, awareness of the criteria and definitions used in the diagnosis of PCOS is important, especially in patients who are being evaluated for ovulatory dysfunction or hyperandrogenism. The imaging report should be specific and should include ovarian volumes and antral follicle counts, in addition to other pertinent findings (eg, the presence of a dominant follicle or corpus luteum). Because patients are frequently referred for radiologic imaging as a part of clinical workup, and polycystic ovaries are a common incidental finding in women undergoing US for other gynecologic complaints, radiologists should be aware of the current diagnostic criteria for PCOS, the role of imaging in workup for this abnormality, and the pertinent reporting parameters for pelvic US.

Serum biomarkers for detecting ectopic pregnancy.

Unless an ectopic pregnancy is visible by ultrasound, diagnosis can be a challenge. Differentiating ectopic pregnancies from intrauterine pregnancies can be impossible without intervention or follow-up. This poses a clinical dilemma to the practitioner given the inherent danger to the mother of tubal rupture of an ectopic pregnancy versus the fear of intervening in the case of a desired pregnancy without certainty of diagnosis. Early diagnostic modalities are clearly lacking, and serum biomarkers are currently being investigated as a solution to need for a rapid and accurate test for ectopic pregnancy.

A cost-effectiveness analysis of surgical versus medical management of early pregnancy loss.

OBJECTIVE: To determine the cost-effectiveness of medical and surgical management of early pregnancy loss. DESIGN: Analyses of cost, effectiveness, and incremental cost-effectiveness ratios and utilities of a multicenter trial with 652 women with first-trimester pregnancy failure randomized to medical or surgical management. SETTING: Analysis of data from a multicenter trial. PATIENT(S): Secondary analysis of a multicenter trial. INTERVENTION(S): Cost-effectiveness analysis. MAIN OUTCOME MEASURE(S): Cost and effectiveness of competing treatment strategies. RESULT(S): Cost analysis of treatment demonstrates an increased cost of US$336 for 13% increased efficacy of surgical management. This analysis was sensitive to the probability of an extra office visit, the cost of the visit, and the probability of success. When the surgical arm is divided into outpatient manual vacuum aspiration (MVA) versus inpatient electric vacuum aspiration (EVA), there is an increased cost of $745 for EVA but a decreased cost of $202 for MVA compared with medical management. In general, MVA was found to be more cost-effective than medical management. For treatment of incomplete or inevitable abortion, medical management was found to be less costly and more efficacious. Utilities studies demonstrated that a patient would need to prefer surgery 14% less than medication for its treatment efficacy to be outweighed by the desire to avoid surgery. CONCLUSION(S): Surgical or medical management of early pregnancy failure can be cost effective, depending on the circumstances. Surgery is cost effective and more efficacious when performed in an outpatient setting. For incomplete or inevitable abortion, medical management is cost effective and more efficacious.

Part 2: Ovarian failure in adolescent cancer survivors should be treated.

Teenage girls who have survived childhood and adolescent cancer are at risk of losing ovarian function as a result of treatment. This iatrogenic complication may compromise their ability to conceive in the future. In addition, the more immediate consequence is interference in the physical, sexual, and psychosocial development of the female adolescent and her ability to "graduate" into young adulthood. This paper lends strong support to meticulous, graduated hormone replacement, mimicking Tanner's stages of pubertal development, to allow smooth transition of adolescent cancer survivors into adulthood.

A disintegrin and metalloprotease protein-12 as a novel marker for the diagnosis of ectopic pregnancy.

OBJECTIVE: To evaluate the performance of a novel biomarker, a disintegrin and metalloprotease-12 (ADAM-12), to differentiate an ectopic pregnancy (EP) from normal intrauterine pregnancies (IUPs). DESIGN: Case-control study. SETTING: Three urban academic centers. PATIENT(S): Women who were seen in the emergency department with pain or bleeding in the first trimester of pregnancy. INTERVENTION(S): Sera from women with diagnosed EP or IUP were evaluated via proteomics and an ADAM-12 dissociation-enhanced lanthanide fluoroimmunoassay. MAIN OUTCOME MEASURE(S): Differences between groups, area under the receiver operating curve, sensitivity, and specificity. RESULT(S): Via a proteomics evaluation, we found a statistically significant decrease in ADAM-12 in the sera of patients with EP, which we confirmed in a larger group of 199 patients (median IUP 18.6 ng/mL versus median EP 2.5 ng/mL with good discrimination between the groups as assessed by receiver operating characteristics [area under the curve = 0.82]). At a low cut-point, the sensitivity was 70% and specificity 84%, but, at a higher cut-point optimizing sensitivity, the ADAM-12 test demonstrated a sensitivity of 97%. CONCLUSION(S): ADAM-12 is a promising marker for the diagnosis of EP in women with symptoms in the first trimester, validating the proteomics findings. Further studies in additional patient populations and in combination with other biomarkers are needed.

Development of a multiple marker test for ectopic pregnancy.

OBJECTIVE: Many serum markers have been proposed to aid in the identification of an ectopic pregnancy, but few have been validated. Most studies have been limited by sample size and design. The goal of this study was to assess putative markers to identify which can be optimally combined. METHODS: We conducted a case-control study using sera from 100 patients with ectopic pregnancy and 100 patients with intrauterine pregnancy who presented to three urban academic centers between September 2000 and April 2009 with first-trimester pain or bleeding. Samples were analyzed for 12 promising biomarkers. Classification tree analysis was used to examine markers simultaneously with the goal of optimizing the accuracy of ectopic pregnancy diagnosis, and validation was performed using bootstrapping. RESULTS: Six of the 12 markers were differentially expressed between those with ectopic pregnancy and intrauterine pregnancy (P<.001) with fair diagnostic properties (area under the curve greater than 0.6) when examined individually (inhibin A, progesterone, activin A, vascular endothelial growth factor [VEGF], pregnancy-specific ß-1-glycoprotein, and pregnancy-associated plasma protein-A). Six additional markers were found to have limited value. Using a two-step diagnostic algorithm with four markers (progesterone, VEGF, inhibin A, activin A), we diagnosed 42% of the sample with perfect specificity and 98% (93-100%) sensitivity. Overall, a single ectopic pregnancy was misclassified, achieving 99% (96-100%) accuracy. CONCLUSION: Evaluating a large number of biomarkers simultaneously demonstrates that most of the putative markers of ectopic pregnancy are not useful. However, a select few can distinguish ectopic pregnancy from intrauterine pregnancy with superior accuracy as part of a multiple marker test. CLINICAL TRIAL REGISTRATION: : ClinicalTrials.gov, www.clinicaltrials.gov, NCT00194168.

The nucleolar channel system reliably marks the midluteal endometrium regardless of fertility status: a fresh look at an old organelle.

OBJECTIVE: To determine whether nucleolar channel systems (NCSs) in the midluteal endometrium are associated with overall fertility status and/or with unexplained infertility. DESIGN: Retrospective and prospective clinical studies. SETTING: Repository of stored specimens from prior multicenter study and private infertility center. PATIENT(S): Retrospective study that included 97 women (49 fertile couples, 48 infertile couples) who had been randomized for endometrial biopsy during the midluteal or late luteal phase. The prospective study included 78 women with a variety of infertility diagnoses. INTERVENTION(S): Endometrial biopsies were obtained and assessed for the presence of NCSs by indirect immunofluorescence. MAIN OUTCOME MEASURE(S): The presence of NCS was graded semiquantitatively and dichotomized as normal versus low or absent. RESULT(S): Normal presence of NCS was significantly associated with the midluteal phase compared with the late luteal phase (80% vs. 29%). However, there was no association between presence of NCS and fertility status or between presence of NCS and unexplained infertility. CONCLUSION(S): Midluteal phase endometrium consistently forms NCSs regardless of fertility status, including unexplained infertility. This indicates a possible role for the NCS in initiating the window of endometrial receptivity. However, the consistent presence of NCSs across several different types of infertility challenges the likelihood that inadequate secretory transformation is a cause of infertility.

Predictors of pregnancy in women with polycystic ovary syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. The selection of first-line therapies for ovulation induction is empiric. OBJECTIVE: The aim of the study was to develop a clinically useful predictive model of live birth with varying ovulation induction methods. DESIGN, SETTING, AND PARTICIPANTS: We built four prognostic models from a large multicenter randomized controlled infertility trial of 626 women with PCOS performed at academic health centers in the United States to predict success of ovulation, conception, pregnancy, and live birth, evaluating the influence of patients' baseline characteristics. INTERVENTIONS: Ovulation was induced with clomiphene, metformin, or the combination of both for up to six cycles or conception. MAIN OUTCOME MEASURE: The primary outcome of the trial was the rate of live births. RESULTS: Baseline free androgen index, baseline proinsulin level, interaction of treatment arm with body mass index, and duration of attempting conception were significant predictors in all four models. History of a prior loss predicted ovulation and conception, but not pregnancy or live birth. A modified Ferriman Gallwey hirsutism score of less than 8 was predictive of conception, pregnancy, and live birth (although it did not predict ovulation success). Age was a divergent predictor based on outcome; age greater than 34 predicted ovulation, whereas age less than 35 was a predictive factor for a successful pregnancy and live birth. Smoking history had no predictive value. CONCLUSIONS: A live birth prediction chart developed from basic clinical parameters (body mass index, age, hirsutism score, and duration of attempting conception) may help physicians counsel and select infertility treatments for women with PCOS.