Pregnancy rates after pre-implantation genetic screening for aneuploidy are only superior when trophectoderm biopsy is performed on hatching embryos.

PURPOSE: In vitro fertilization with trophectoderm embryo biopsy and pre-implantation genetic screening with comprehensive chromosomal screening (PGS-CCS) for aneuploidy is becoming increasingly more popular. Embryos are cryopreserved and implanted in a subsequent frozen thawed embryo transfer cycle (FET). No studies have investigated differences in pregnancy outcomes by timing of trophectoderm biopsy relative to stages of blastocyst development. METHODS: Retrospective study of all patients (n = 363) at a single IVF center between January 1, 2013 and December 31, 2016 undergoing single embryo transfer with PGS-CCS where embryos were cryopreserved with subsequent FET. Embryo expansion and grading was assessed both at the time of biopsy and transfer. Pregnancy rates were analyzed by embryo expansion and embryo grading. RESULTS: Implantation, clinical pregnancy, and live birth rates improved significantly with increased embryo expansion at the time of embryo biopsy (P < 0.001). Pregnancy loss decreased with increases in embryo expansion prior to biopsy (P < 0.001). Superior live birth rates with PGS-CCS were seen when embryos were hatching at the time of biopsy (p < 0.001). For fresh and frozen embryo transfers without PGS-CCS, embryo expansion did not affect pregnancy outcomes. CONCLUSIONS: PGS-CCS significantly increases implantation and live birth rates only if embryos are hatching at the time of biopsy. The embryo biopsy itself on a non-hatching embryo significantly damages the embryo in ways which are not reflected in future embryo expansion. IVF labs should wait until embryos hatch before performing trophectoderm biopsy.

Initial maternal serum human chorionic gonadotropin levels in pregnancies achieved after assisted reproductive technology are higher after preimplantation genetic screening and after frozen embryo transfer: a retrospective cohort.

PURPOSE: Few published articles have compared initial hCG values across all different types of ART cycles, including cycles with fresh or frozen embryo transfer. No articles have compared initial hCG values in cycles utilizing preimplantation genetic screening (PGS). The purpose of this study is to compare initial hCG values after fresh embryo transfer, frozen embryo transfer, and after PGS. METHODS: This was a single-center retrospective cohort study at an academically affiliated private IVF center. All fresh and frozen embryo transfers between January 2013 and December 31, 2015 were included. We compared mean initial serum hCG values 14 days after oocyte retrieval for fresh cycles and 9 days after frozen embryo transfer. We examined cycles of single embryo transfer (SET) and double embryo transfer (DET). RESULTS: Two hundred elven IVF (fresh embryo transfer), 128 FET (frozen embryo transfer cycles, no PGS), and 111 PGS cycles (ovarian stimulation with embryo cryopreservation, PGS, and frozen transfer in a subsequent estrogen-primed cycle) with initial positive hCG values were analyzed. In patients achieving a positive hCG after SET, initial hCG values were higher after PGS compared to FET (182.4 versus 124.0 mIU/mL, p = 0.02) and IVF (182.4 versus 87.1 mIU/mL, p < 0.001) as well as FET compared to IVF (124.0 versus 87.1 mIU/mL, p < 0.01). After DET, initial hCG values were higher after PGS (222.8 mIU/mL) compared to FET (182.1 mIU/mL, p = 0.02) and IVF (131.1 mIU/mL, p = 0.001). CONCLUSIONS: Our study suggests that initial serum hCG values are higher after using PGS and higher after the transfer of a frozen embryo compared to a fresh embryo. This suggests that initial hCG values relate to the chromosomal status of embryos. Initial hCG values may help determine intervention and monitoring later in pregnancy.

Use of Concomitant FSH with hCG at the Time of Trigger May Improve Success Rates of Couples with Poor Ovarian Response Undergoing Gonadotropin Therapy with IUI.

OBJECTIVE: To investigate if administration of an additional dose of gonadotropins concomitantly to human chorionic gonadotropin (hCG) trigger increases pregnancy rates in patients undergoing intrauterine insemination (IUI) with controlled ovarian hyperstimulation (COH). STUDY DESIGN: This is a retrospective cohort study of all gonadotropin-IUI cycles performed by a single physician in a private practice between January 2012 and September 2013. Control cycles were those in which follicle-stimulating hormone (FSH) was discontinued prior to the day of hCG trigger shot, and study cycles received continuous FSH including the day of hCG trigger shot. A total of 423 cycles from 239 patients were included; 275 (65.5%) were control cycles (137 patients), and 146 (34.7%) were study cycles (102 patients). RESULTS: Pregnancy rates were comparable in both control and study groups (15.27% vs. 15.07%, respectively, p=0.956). There was a 42% increase in multiple gestations in the study group; however, the difference was not statistically significant (p=0.155). Upon multivariate logistic regression, male factor infertility was the only variable that was associated with pregnancy outcomes. CONCLUSION: Continuous administration of FSH including the day of hCG trigger in patients undergoing COH with IUI does not seem to increase pregnancy rates. Our suggested protocol might be beneficial in patients with poor ovarian response.

The presence of multiple gestational sacs confers a higher live birth rate in women with infertility who achieve a positive pregnancy test after fresh and frozen embryo transfer: a retrospective local cohort.

BACKGROUND: After spontaneous conception, the rate of miscarriage is more common in multiple rather than singleton pregnancies. However, the incidence of miscarriage is lower in in-vitro fertilization twin versus singleton pregnancies. Most patients have little understanding of pregnancy outcomes once they achieve a positive pregnancy test. This study investigated the relationship between multiple pregnancy and miscarriage in women with infertility after fresh and frozen embryo transfer. METHODS: Retrospective local cohort study of all consecutive patients undergoing in-vitro fertilization at our institution (n = 1130), fresh or frozen embryo transfer, between January 1, 2008 and December 31, 2012. Patient characteristics (age, body mass index, initial hCG, maximum follicle stimulating hormone levels) and in-vitro fertilization parameters (estradiol levels, eggs retrieved, and endometrial thickness) were collected and statistically analyzed using T-test and Chi-square test (Stata version 10). Linear and logistic regression were used when appropriate. RESULTS: Overall, live birth rate for all cycles was 30.44% and total pregnancy loss was 6.55% - similar for fresh and frozen cycles despite a higher rate of biochemical pregnancies for frozen cycles. Among all pregnant patients, 62.48% had a live birth. Although clinical pregnancy rate was higher for fresh cycles, live birth rates were similar. In pregnancies where multiple sacs were demonstrated on ultrasound, live birth rates were higher despite 31% of patients losing at least one sac. This finding was comparable between fresh and frozen cycles. However, in patients under age 35 and using donor egg, no live birth advantage was seen in patients with multiple sacs. In fact, transferring more than one embryo did not increase live birth rate either. CONCLUSIONS: Despite the many maternal and fetal risks of multiple pregnancies, patients who achieve a positive pregnancy test with fresh and frozen in-vitro fertilization and who have more than one pregnancy sac are more likely ultimately to deliver at least one baby. This finding is true of both fresh and frozen embryo transfer cycles. This pregnancy advantage is not seen in young patients and in patients using donor egg, and single embryo transfer maximizes birth outcomes.

Live birth of a normal mature healthy baby by in vitro fertilization-embryo transfer (IVF-ET) after an exploratory laparotomy and multiple myomectomy for leiomyomatosis peritonealis disseminata.

OBJECTIVE: To report a case of a live birth of a normal mature healthy baby by IVF-ET after an exploratory laparotomy and multiple myomectomy for leiomyomatosis peritonealis disseminata. DESIGN: Case report. SETTING: Academic university hospital. PATIENT(S): A 37-year-old female G2P0 with secondary infertility diagnosed with leiomyomatosis peritonealis disseminata who underwent surgical resection and IVF stimulation. INTERVENTION(S): One cycle of IVF-ET initiated with Gonal F and Menopur. MAIN OUTCOME MEASURE(S): Live birth of a normal mature healthy baby. CONCLUSION(S): IVF-ET can produce a normal healthy baby in a patient with leiomyomatosis peritonealis disseminata.

Impact of obesity on the risk for polycystic ovary syndrome.

CONTEXT: Although it is well established that adiposity increases the severity of the clinical features of polycystic ovary syndrome (PCOS), the data regarding the prevalence of PCOS in obese women and the change in body weight women presented with PCOS over time are scarce. OBJECTIVE: The objective of the study was to determine whether obesity increases the risk of PCOS and whether the degree of obesity of PCOS patients has increased, paralleling the rise in obesity in the population. DESIGN: We analyzed data from two consecutive populational studies assessing the prevalence of PCOS and a database containing all untreated PCOS patients evaluated at a university clinic between 1987 and 2002. SETTING: The study was conducted at a tertiary care center. PATIENTS OR OTHER PARTICIPANTS: Participants included 675 women who participated in prevalence studies and 746 PCOS patients. MAIN OUTCOME MEASURES: Populational prevalence of PCOS according to body mass index (BMI) and change in BMI of PCOS patients over time were measured. RESULTS: The prevalence rates of PCOS in underweight, normal-weight, overweight, and obese women were 8.2, 9.8, 9.9, and 9.0%, respectively. Prevalence rates reached 12.4 and 11.5% in women with BMI 35-40 kg/m2 and greater than 40 kg/m2 (P = NS). The mean BMI of PCOS patients diagnosed between 1987 and 2002 rose, beginning in 1997 and reaching 37.3 +/- 9.9 kg/m2 in 2000-2002, paralleling the change in BMI of the surrounding population (10-14% obesity rate in 1987, 15-19% in 1997, and 25% or greater in 2002). CONCLUSION: Our results suggest that the risk of PCOS is only minimally increased with obesity, although the degree of obesity of PCOS patients has increased, similar to that observed in the general population. These data indicate that obesity in PCOS reflects environmental factors to a great extent.

Phenotypic spectrum of polycystic ovary syndrome: clinical and biochemical characterization of the three major clinical subgroups.

OBJECTIVE: We tested the hypothesis that the three clinical phenotypes of polycystic ovary syndrome (PCOS) represent forms of the same metabolic disorder. DESIGN: Prospective cohort analysis. SETTING: University-based tertiary care. PATIENT(S): Three-hundred sixteen untreated consecutive women diagnosed as having PCOS. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Each subject underwent an evaluation of ovulatory function, body habitus, acne, and hirsutism; serum free and total testosterone (T), 17-hydroxyprogesterone (17-HP), and DHEAS; and fasting plasma glucose and insulin levels. Insulin resistance and beta-cell function were assessed using the homeostatic assessment model equation (HOMA-IR and HOMA-beta-cell, respectively). RESULT(S): The Oligo+HA+Hirsutism phenotype was present in 48% of subjects, Oligo+HA in 29%, and Oligo+Hirsutism in 23%. The three phenotypes did not differ in mean body mass index, waist-to-hip ratio, racial composition, degree of oligo-ovulation, prevalence of acne, or family history of hyperandrogenic symptomatology. However, subjects demonstrating the Oligo+HA+Hirsutism phenotype were the youngest and had the greatest degrees of hyperandrogenemia, hyperinsulinemia, and beta-cell function; patients with the Oligo+Hirsutism phenotype where the oldest and had the mildest degrees of hyperandrogenemia, hyperinsulinemia, and beta-cell function. Subjects with the Oligo+HA phenotype demonstrated intermediate degrees of hyperandrogenemia and metabolic dysfunction. CONCLUSION(S): We conclude that the three clinical phenotypes of PCOS do not represent forms of the same metabolic disorder and may be the result of varying degrees of metabolic dysfunction; greater degrees of beta-cell function and circulating insulin levels favored the development of hirsutism and frank hyperandrogenemia.

Early adrenarche in normal prepubertal girls: a prospective longitudinal study.

OBJECTIVE: To study basal and ACTH stimulated levels of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), and cortisol (F) in healthy girls during prepuberty. PATIENTS: Six prepubertal girls, ages 3.7-10.9 years. STUDY DESIGN AND MEASUREMENTS: The six girls underwent a physical examination and an acute ACTH stimulation test on a yearly basis. Serum DHEA, DHEAS, A4, and F at 0 min (Steroid0) and 60 min (Steroid60) after 0.25 mg ACTH1-24 i.v., and the net increment (delta Steroid60-0) were calculated. RESULTS: DHEAS0, DHEAS60, DHEA0, DHEA60 and A40 were positively correlated to chronological age. DHEAS0 and DHEAS60 levels rose gradually beginning at 6.1-7.0 years of chronological age, and were found to be significantly different at 9.1-10.0 years and 10.1-11.0 years of age, compared to the median values obtained at < or =6.0 years of age. There was a tendency for DHEA0, DHEA60, and A40 to increase beginning at 9.1-10.0 years of age. Net increment values of all hormones did not change throughout the study. CONCLUSION: An increase in the circulating level of DHEAS appears to be the first event observed during adrenarche, prior to clinical evidence of the process.

The prevalence and features of the polycystic ovary syndrome in an unselected population.

Notwithstanding the potential public health impact of the polycystic ovary syndrome (PCOS), estimates regarding its prevalence are limited and unclear. Between July 1998 and October 1999, 400 unselected consecutive premenopausal women (18-45 yr of age) seeking a preemployment physical at the University of Alabama at Birmingham were studied (223 Black, 166 White, and 11 of other races). Evaluation included a history and physical examination, a modified Ferriman-Gallwey hirsutism score, and serum screening for hyperandrogenemia, hyperprolactinemia, and 21-hydroxylase-deficient nonclassical adrenal hyperplasia. PCOS was diagnosed by the presence of the following: 1) oligoovulation, 2) hyperandrogenemia and/or hirsutism (modified Ferriman-Gallwey score > or = 6), and 3) the exclusion of related disorders. Confirmed PCOS was established in those individuals whose evaluation was complete and indicative of PCOS, and possible PCOS was established when the hormonal evaluation was not complete or was unavailable, but the clinical phenotype was otherwise suggestive of the disorder. The individual probability of PCOS in women with possible PCOS was assigned a weight based on the findings in similar subjects whose evaluation was complete, and the total number of PCOS cases arising from these individuals was calculated (i.e. individual probability of PCOS x total number of subjects in the group). The cumulative prevalence of PCOS in our population was 6.6% (26.5 of 400), including 15 subjects among the 347 women completing their evaluation and a calculated prevalence of 11.5 subjects among the remainder. The prevalence rates of PCOS for Black and White women were 8.0 and 4.8%, respectively, not significantly different. These data from a large representative unselected population support the concept that PCOS is the most common endocrine abnormality of reproductive-aged women in the United States.

Glucose action and adrenocortical biosynthesis in women with polycystic ovary syndrome.

OBJECTIVE: To determine if insulin or glucose action plays a role in adrenocortical steroidogenesis in the polycystic ovary syndrome (PCOS). DESIGN: Prospective cohort study. SETTING: Academic medical center. PATIENT(S): Nine reproductive-aged patients with PCOS and nine age-, race-, and body mass index-matched controls. MAIN OUTCOME MEASURE(S): Insulin-modified frequently sampled intravenous glucose tolerance testing and an acute 60-minute ACTH-(1-24) stimulation test. From the glucose tolerance test, glucose and insulin were measured and the insulin sensitivity index, glucose effectiveness, and acute insulin response to glucose were determined. Dehydroepiandrosterone sulfate (DHEAS) basally and 17-hydroxypregnenolone, 17-hydroxyprogesterone, DHEA, androstenedione, and cortisol during ACTH testing at 0 and 60 minute (steroid(0) and steroid(60)) were determined. The net change in steroid during the ACTH test was calculated. RESULT(S): The insulin sensitivity index had limited correlation with adrenocortical variables in both groups. In patients with PCOS, glucose effectiveness was positively associated with DHEAS, cortisol(0), cortisol(60), change in cortisol, DHEA(0), DHEA(60), change in DHEA, 17-hydroxyprenenolone(60), change in 17-hydroxypregnenolone, DHEA(0), androstenedione(0), 17-hydroxyprenenolone(0), 17-hydroxyprogesterone(0), 17-hydroxyprenenolone(60), and 17-hydroxyprogesterone(60). CONCLUSION(S): Adrenocortical biosynthesis, basally and in response to ACTH, appears to be closely associated with glucose effectiveness in PCOS. A common factor determining both the effectiveness of glucose to control its own production or uptake and adrenocortical biosynthesis may be aberrant in PCOS.