To curette or not to curette; efficiency of oocyte retrieval technique.

PURPOSE: Follicular curetting is the gentle and rapidly rotating movement of the aspiration needle in a clockwise and counterclockwise fashion. The aim of our study is to assess this retrieval technique comparing cycle and pregnancy outcomes between curetting and non-curetting. METHODS: This was a retrospective review of 817 patients that underwent oocyte retrieval at our fertility center from January 1st, 2016 until August 31st, 2019. All patients enrolled in the study underwent standard ovarian stimulation protocols. Three physicians routinely utilized follicle curetting during oocyte retrieval, while a fourth physician did not curette. Retrievals and embryo transfers were performed based on a rotating physician schedule. RESULTS: Retrievals that were performed using a curetting technique had a significantly higher number of total oocytes retrieved 12.4 ± 8.1 vs 10.7 ± 7.5 (p = 0.01), and number of M2 oocytes retrieved 8.1 ± 6.4 vs 6.9 ± 6.0 (p = 0.03), resulting in an increased M2 oocyte yield 63.7% ± 41.3 vs 50.9% ± 30.6 (p = 0.0001). These patients also had a significant increase in clinical pregnancy rate per retrieval 55 vs 41% (p = 0.0016), live birth rate per retrieval 42 vs 34% (p = 0.04) and with no significant difference in multiple gestations or OHSS. CONCLUSIONS: A significant improvement in clinical pregnancy rates and live birth per retrieval was detected in patients undergoing curetting. These patients had more embryos frozen, leading to more transfers and more successful pregnancies.

Assessment of uterine receptivity by endometrial and sub-endometrial blood flow using SlowflowHD in hormone prepared frozen embryo transfer cycles: a pilot study.

PURPOSE: Utilizing SlowflowHD as a measurement of endometrial and sub-endometrial blood flow in women with infertility undergoing frozen embryo transfer (FET) cycles and correlation with pregnancy outcomes. METHODS: A prospective pilot study of 99 women undergoing hormone replacement FET cycles. Ultrasounds were performed with Voluson E8 at 3-time points: day 15, day of transfer, and 11 days post transfer (T + 11). SlowflowHD Doppler blood flow indices in the endometrium and sub-endometrium were compared in women who achieved pregnancy with those who did not. RESULTS: Using SlowflowHD, both pregnant and non-pregnant women had similar trends with decreased endometrial blood flow day of transfer compared with day 15. However, there was a borderline significantly lower mean percentage decrease of endometrial blood flow in women achieving a pregnancy (28.3% vs 42.9%). Significantly higher numbers of pregnant women had a 20% or less decrease in blood flow (21 vs 9) with increases in mean percentage blood flow on T + 11 (pregnant 39.59% vs non-pregnant 25.20%). The RI and S/D ratio in the spiral arteries was also significantly higher on transfer day in women who had a live birth RI (0.68 vs 0.65) and S/D (3.91 vs 3.17). CONCLUSION: There are blood flow changes both in pregnant and non-pregnant patients with decreases in blood flow after progesterone replacement. Pregnancy and live births were associated with a lower mean percentage drop in blood flow from day 15 to the day of transfer and elevated RI and S/D ratio on transfer day.

Changing gender gap and practice patterns in reproductive endocrinology and infertility subspecialists in the United States: a Society for Reproductive Endocrinology and Infertility report.

OBJECTIVE: To identify changes in current practice patterns, salaries, and satisfaction by gender and by years in practice among board-certified reproductive endocrinology and infertility (REI) subspecialists in the United States. DESIGN: Cross-sectional web-based survey including 37 questions conducted by the Society for Reproductive Endocrinology and Infertility. SETTING: Not applicable. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome measures were total compensation and practice patterns compared by gender and the type of practice. The secondary outcomes included demographics, the number of in vitro fertilization cycles, surgeries performed, and the morale of survey respondents. RESULT(S): There were 370 respondents (48.4% women and 51.4% men). Compared with a similar survey conducted 6 years earlier, a 27% increase in the number of female respondents was observed in this survey. There was a marginally significant trend toward lower compensation for female than male REI subspecialists (17% lower, $472,807 vs. $571,969). The gap was seen for responders with ≥10 years' experience, which is also when there was the largest gap between private and academic practice (mean $820,997 vs, $391,600). Most (77%) felt positively about the current state of the reproductive endocrinology field, and >90% would choose the subspecialty again. CONCLUSION(S): There has been a substantial increase in the number of recent female REI subspecialists showing less disparity in compensation, and the gap appears to be closing. There is an increasing gap in compensation between private and academic practices with ≥5 years of experience. Reproductive endocrinology and infertility remains a high morale specialty.

Patterns of Bariatric Surgeries Among U.S. Women Diagnosed with Polycystic Ovarian Syndrome.

Background: To examine patterns and outcomes of bariatric surgeries, including Roux-en-Y gastric bypass (RYGB), laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding (LAGB), among women diagnosed with polycystic ovarian syndrome (PCOS). Materials and Methods: Retrospective cohort study using 1998-2011 Nationwide Inpatient Sample data. A total of 52,668 hospital discharge records met eligibility criteria among PCOS women, 18-49 years. Of those, 17,759 had an obesity/overweight diagnosis and 4310 underwent bariatric surgery. Furthermore, 3086 underwent RYGB (n = 2411), LSG (n = 126), or LAGB (n = 549), and were compared to 78,931 non-PCOS controls. Multiple regression models were constructed to examine patient- and hospital-level predictors of obesity/overweight and bariatric surgery, as well as type of bariatric surgery (RYGB, LSG, or LAGB) as a predictor of in-hospital outcomes and PCOS status. Results: The prevalence of obesity/overweight (≈34%) among women diagnosed with PCOS, and of bariatric surgery (≈24%) among women diagnosed with PCOS and obese/overweight varied by patient- and hospital-level characteristics. Women having PCOS and overweight/obesity, who underwent LSG or LAGB, had shorter hospital stay, reduced hospital charges, and better disposition at discharge compared to those who underwent RYGB. PCOS cases and non-PCOS controls experienced similar treatment selection and in-hospital outcomes after bariatric surgery. Also, PCOS cases and non-PCOS controls experienced similar in-hospital outcomes after undergoing RYGB, LSG, or LAGB. Conclusions: Compared to RYGB, LSG and LAGB resulted in improved in-hospital outcomes among obese/overweight PCOS and non-PCOS patients. Further research is needed to examine health care disparities in the context of PCOS, obesity/overweight, and bariatric surgery.

Knowledge and attitudes regarding elective oocyte cryopreservation in undergraduate and medical students.

BACKGROUND: To assess knowledge and attitudes regarding elective oocyte cryopreservation among female undergraduate students (UG) and medical students (MS) in Eastern Virginia. METHODS: An anonymous cross-sectional study surveying female UG at a local university and MS at our academic medical center in May of 2017. The survey contained questions on demographic information, interest in fertility preservation, and knowledge about age related changes in fertility. RESULTS: There were 74 of 102 female UG and 95 of 117 female MS who responded, for a response rate of 73 and 81% respectively. UG were significantly younger than MS (21.4 vs 26.8, p < 0.001). Further, UG generally planned on conceiving at a younger age than MS (age 26-30 vs 31-35), and favored younger ages to consider oocyte cryopreservation (age 26-30 vs 31-35). Only a minority of both UG and MS were willing to undergo egg freezing at the current price of approximately $10,000 (15% vs 26% respectively, p = 0.044). Moreover, 73% of students overall responded that they would be more likely to freeze oocytes if their employer paid. Notably, both UG and MS underestimated age of fertility decline. CONCLUSION: Both UG and MS revealed a need for education on age-related changes in fertility. Most UG and MS would not undergo elective oocyte cryopreservation at the present cost but would consider it at a lower cost.

Gynecologic Surgery: Preoperative Assessment With Ultrasound.

Ultrasonography, especially 3D, is essential in the diagnosis and preoperative evaluation of gynecologic surgeries and is important in surgical planning and counseling of patients. In addition, it is useful during hysteroscopic procedures, particularly difficult Asherman syndrome cases, resection of transverse vaginal septum, and treatment of hematometria. 3D ultrasound is especially helpful for fibroid mapping as the simultaneous visualization of the endometrium and myometrium with the coronal view is possible, it can be done by the gynecologist and at a lower cost than an magnetic resonance imaging. The ability to visualize with ultrasound during surgery may reduce complications and eliminate the use of laparoscopy.

Progesterone vaginal ring for luteal support.

Progesterone supplementation is universally used and has been shown to be beneficial in supplementation of the luteal phase in IVF. There are multiple options and the most commonly used include intramuscular and vaginal progesterone. A progesterone vaginal ring is a novel system for luteal support with advantages of controlled release with less frequent dosing. This review examines options for progesterone luteal support focusing on the rationale for a progesterone vaginal ring. Pub-med search of the literature. A weekly vaginal ring, although not yet FDA approved, is an effective and safe alternative for luteal supplementation in IVF. Large prospective clinical trials are needed to determine the best protocols for replacement cycles.

Impact of serum estradiol levels on the implantation rate of cleavage stage cryopreserved-thawed embryos transferred in programmed cycles with exogenous hormonal replacement.

PURPOSE: To investigate the impact of late follicular phase serum estradiol (E2) levels on implantation and pregnancy outcomes of cleavage stage cryopreserved/thawed embryos transferred in programmed cycles with exogenous hormonal replacement. METHODS: Retrospective cohort analysis of IVF patients with transfer of cryopreserved-thawed day-3 embryos in E2 and progesterone (P4) supplemented cycles (n = 208 cycles). MAIN OUTCOME MEASURES: implantation and pregnancy rates according to late follicular phase serum E2 levels and early secretory phase E2/P4 ratios. RESULTS: Logistic regression performed for embryo implantation and for pregnancy outcome in relation to E2 (day 15), P4 (day 15 and 16), before (crude analysis) and after adjustment (adjusted analysis) for baseline characteristics (including age, BMI, serum basal cycle day 3 FSH levels, embryo quality, endometrial lining thickness) showed no significant association. Similarly, ROC analysis showed no impact of cycle day 16 E2/P4 ratio. CONCLUSIONS: Neither late follicular phase serum E2 nor the early E2/P4 ratio were able to predict implantation or pregnancy outcome of day-3 cryopreserved-thawed embryos transferred in artificially programmed cycles.

Progesterone vaginal ring versus vaginal gel for luteal support with in vitro fertilization: a randomized comparative study.

OBJECTIVE: To compare the efficacy and safety of luteal phase support in IVF with a progesterone (P) vaginal ring or gel (VR or VG). DESIGN: Prospective, randomized, single-blind, multicenter, phase III clinical trial (ClinicalTrials.gov identifier: NCT00615251). SETTING: Nineteen private and three academic high-volume U.S. IVF centers. PATIENT(S): One thousand two hundred ninety-seven infertile patients were randomized to a weekly P VR (n = 646) or a daily P 8% VG (n = 651). INTERVENTION(S): IVF was performed per site-specific protocols. The day after egg retrieval, patients were randomized and began VR or VG therapy, which continued for up to 10 weeks' gestation. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates at 8 and 12 weeks of pregnancy; rates of biochemical pregnancy, live birth, spontaneous abortion, ectopic pregnancy, and cycle cancellation; and safety and tolerability were secondary measures. RESULT(S): Clinical pregnancy rates at 8 and 12 weeks were high and comparable between groups: 48.0% for VR and 47.2% for VG at week 8 and 46.4% (VR) and 45.2% (VG) at week 12. Live-birth rates were 45% (VR) and 43% (VG). Adverse event profiles were similar between groups. CONCLUSION(S): The weekly P VR provided similar pregnancy rates to the daily VG, with no major differences in safety.

Patterns of use of insulin-sensitizing agents among diabetic, borderline diabetic and non-diabetic women in the National Health and Nutrition Examination Surveys.

The purpose of this cross-sectional study based on the 2001-2006 National Health and Nutrition Examination Survey is to examine demographic, socioeconomic, lifestyle and reproductive characteristics that may distinguish users and non-users of insulin sensitizing agents among the US diabetic, borderline diabetic and non-diabetic women. Use of insulin-sensitizing agents was evaluated among 19,579 (3882 diabetic, 387 borderline diabetic and 15,310 non-diabetic) women. Overall, 2% of women in the study sample were users of insulin-sensitizers, including metformin, rosiglitazone and pioglitazone. Multivariate logistic regression models were constructed for predictors of insulin-sensitizer use according to diabetic status. In the overall sample, being younger or diabetic were the only factors associated with an increased odds of using insulin-sensitizing agents, after adjustment of confounders. Among diabetics, use of insulin-sensitizing agents was inversely related to age, but not other factors in the multivariable model. Among borderline and non-diabetics, body mass index (BMI) was the only predictor that remained significantly associated with the use of insulin-sensitizing agents after controlling for confounders. In conclusion, the main predictors of insulin-sensitizer use are young age and diabetic status in all women, young age in diabetic women and high BMI in borderline and non-diabetic women.

Does the degree of hypothalamic-pituitary-ovarian recovery after oral contraceptive pills affect outcomes of IVF/ICSI cycles receiving GnRH-antagonist adjuvant therapy in women over 35 years of age?

PURPOSE: To evaluate if the degree of recovery of serum gonadotropins after oral contraceptive pills (OCP) pretreatment has an impact on ovarian response in GnRH-antagonist IVF cycles in women of advanced maternal age. METHODS: In this retrospective cohort study, we included 98 women 35-42 years undergoing their first IVF cycle receiving gonadotropins and a fixed GnRH-antagonist adjuvant protocol. Data analysis was carried out according to changes in serum FSH, LH and estradiol (E(2)) levels (basal and post-OCP) divided in quartiles, and also according to absolute levels. The main outcomes were peak serum E(2), number of mature oocytes retrieved, length of stimulation, and amount of gonadotropins used. RESULTS: By quartile analysis, patients with the highest levels of serum gonadotropins suppression and also patients with gonadotropin rebound needed larger amounts of LH during the treatment. On the other hand, women with absolute suppression of FSH/LH had increased length of stimulation. CONCLUSIONS: The results of this study provide data that assist in clinical management. Gonadotropin serum levels after OCP treatment provide information for optimization of supplementation with LH in GnRH-antagonist cycles in women over age 35.

A study of the cost, accuracy, and benefits of 3-dimensional sonography compared with hysterosalpingography in women with uterine abnormalities.

OBJECTIVES: We conducted a prospective blinded study to evaluate the costs, accuracy, risks, and benefits of 3-dimensional (3D) transvaginal sonography compared to hysterosalpingography. METHODS: A total of 101 women aged 26 to 44 years with evidence of uterine anomalies were enrolled. All participants had routine hysterosalpingography as part of their infertility evaluation as well as 3D transvaginal sonography as part of the study. Surgical findings were used as the standard for final diagnosis. RESULTS: A total of 6 normal uteri and 119 uterine anomalies were classified: 30 congenital uterine anomalies (3 arcuate, 1 unicornuate, 4 bicornuate, 2 didelphys, and 20 septate uteri) and 89 acquired anomalies (38 polyps, 30 fibroids, 17 synechiae, and 4 adenomyosis). Congenital anomalies were correctly identified in 30 of 30 cases by 3D sonography but from 10 to 30 of 30 cases by hysterosalpingography. The detection rates for acquired uterine anomalies were lower for both techniques: 44 to 89 of 89 cases for 3D sonography and 22 to 74 of 89 cases for hysterosalpingography. Only 7 of the 20 septi would have been surgically corrected if patients only had hysterosalpingography. On the contrary, 30 of 30 patients with congenital uterine anomalies, 2 of 4 patients with adenomyosis, and all 6 patients with normal uteri were spared from surgery with diagnoses by 3D sonography. No adverse effects were reported after sonography, and only 6 minor ones were reported after hysterosalpingography. CONCLUSIONS: Three-dimensional transvaginal sonography provides visualization and evaluation of the uterine cavity with similar or better accuracy than standard hysterosalpingography in the office setting, with lower cost and morbidity.

Relationship of obesity-related disturbances with LH/FSH ratio among post-menopausal women in the United States.

OBJECTIVES: Although luteinizing hormone to follicular stimulating hormone (LH/FSH) ratio is a controversial criterion for identifying a sub-group of infertile women with polycystic ovary syndrome (PCOS) and abnormalities at the level of the hypothalamic-pituitary-ovarian axis, an elevated LH/FSH ratio is frequently observed in PCOS cases. Obesity and insulin resistance are highly prevalent among PCOS women. To date, no studies have examined the associations of LH/FSH ratio with these co-morbid conditions outside the context of pre- and peri-menopausal PCOS women. The objective of this study is to evaluate whether the LH/FSH ratio is associated with obesity, insulin resistance, metabolic disturbances and chronic inflammation among post-menopausal U.S. women, 35-60 years of age. STUDY DESIGN: Cross-sectional study of 693 women who participated in the 1999-2002 National Health and Nutrition Examination Survey. MAIN OUTCOME MEASURES: Body mass index, waist circumference, triglycerides, high-density lipoprotein (HDL) cholesterol, systolic and diastolic blood pressures, fasting glucose, metabolic syndrome, Homeostasis Model Assessment for Insulin Resistance and C-reactive protein (CRP). RESULTS: Age- and hysterectomy-adjusted regression models suggest that CRP level is positively associated with LH/FSH ratio and LH/FSH>1, high glucose level and LH/FSH>2 are inversely related and HDL<50mg/dL is positively associated with both LH/FSH>1 and LH/FSH>2. CONCLUSIONS: In a nationally representative sample of post-menopausal women, markers of chronic inflammation and dyslipidemia which are characteristics of PCOS-associated morbidities were also significantly associated with LH/FSH ratio, meriting further investigation.

Timing of oocyte retrieval and embryo transfer with pregnancy duration.

BACKGROUND: Recent studies have suggested that assisted reproductive technology (ART) may be associated with a shorter pregnancy duration, possibly due to various aspects of the ART procedure. The purpose of this study was to examine whether pregnancy duration is affected by timing of oocyte retrieval and embryo transfer with respect to the first day of the last menstrual period (LMP) among pregnancies achieved through in vitro fertilization with or without intracytoplasmic sperm injection. METHODS: A retrospective study was conducted at an academic center in Norfolk, Virginia, with analyses based on 294 ART cycles. RESULTS: Median and interquartile range for pregnancy duration was estimated at 38.2 ± 3.4 weeks. Similarly, median and interquartile ranges for days between LMP and day of oocyte retrieval (27.0 ± 2.0) and between LMP and embryo transfer (29.8 ± 2.2) differed significantly from the standard of 14 days. Timing of oocyte retrieval and embryo transfer with respect to LMP were accelerated among multiple compared with single gestations. For single gestations, pregnancy duration was positively associated with time duration between LMP and embryo transfer (ß=0.14, p=0.036). The number of days between oocyte retrieval and embryo transfer was marginally associated with a shorter pregnancy duration in women with multiple gestations (ß=3.70, p=0.083). Controlling for patient characteristics, timing of oocyte retrieval and embryo transfer were not significantly associated with pregnancy duration. CONCLUSIONS: With few exceptions, timing of oocyte retrieval or embryo transfer did not affect pregnancy duration among ART-conceived live births.

Successful extracorporeal mature oocyte harvesting after laparoscopic oophorectomy following controlled ovarian hyperstimulation for the purpose of fertility preservation in a patient with borderline ovarian tumor.

PURPOSE: To report the successful extracorporeal recovery of mature oocytes after laparoscopic oophorectomy following ovarian hyperstimulation for the purpose of fertility preservation in a patient with recurrent serous borderline ovarian tumor. METHODS: A 25-year-old nulligravida woman presented with recurrence of a borderline serous adenocarcinoma in the right ovary after been treated conservatively with left oophorectomy for the same. RESULT(S): The patient underwent ovarian stimulation followed by a laparoscopic oophorectomy and ex-vivo retrieval of oocytes. Twenty two oocytes were recovered: fourteen metaphases II, two metaphases I, five prophases I and one degenerate. CONCLUSION(S): Mature oocytes were successfully retrieved ex-vivo from the hyperstimulated ovary recovered via laparoscopy. The procedure can be performed in a quick manner, with standard equipment, without damaging the ovary, the follicles or the oocytes, and without the risk of cancer cell spillage associated with the standard transvaginal oocyte retrieval if there is concern of ovarian surface/peritoneal metastatic disease.

Gonadotrophin ovulation induction and enhancement outcomes: analysis of more than 1400 cycles.

Ovulation induction (OI) or ovulation enhancement (OE) with gonadotrophins can be a reasonable treatment option for patients with a variety of infertility diagnoses. It must be used with extensive monitoring and management given the risk of multiple pregnancy,especially high-order multiples. This retrospective study evaluated per cycle outcomes of a large cohort of 1452 gonadotrophin OI/OE cycles at an academic infertility centre, and the efficacy of specific guidelines in limiting multiple pregnancy. The lowest possible gonadotrophin doses were used and cycle cancellation was recommended if more than three dominant follicles were present, and/or ifserum oestradiol was above 1500 pg/ml. Overall, pregnancy rate (PR) was 12% and live birth rate was 7.7%, with an increasing trend in younger patients (P = 0.0002 and <0.0001, respectively). Multiple clinical PR was 2.6% with 1.9% twins and 0.7% triplets and above.The birthweight of a singleton from a vanishing twin pregnancy (n = 8)was significantly lower than other singletons (2882 g versus 3250 g,P = 0.013). Reducing multiple pregnancies from OI/OE cycles remains an important and challenging goal. In this large cohort, high-order multiple clinical PR was limited to 0.7% per cycle by using specific management strategies while maintaining a reasonable PR.

Live birth from a frozen-thawed pronuclear stage embryo almost 20 years after its cryopreservation.

OBJECTIVE: To report a live birth after transfer of cryopreserved pronuclear embryos in cryostorage for almost 20 years. DESIGN: Case report. SETTING: Academic IVF center. PATIENT(S): A 42-year-old female patient with low ovarian reserve receiving donated embryos. These embryos were the result of an anonymous donation from an infertile couple who had conceived during her IVF treatment. INTERVENTION(S): Cryopreservation (slow-freeze method) and thawing of pronuclear stage embryos, and ultrasound-guided uterine ET. MAIN OUTCOME MEASURE(S): Live birth. RESULT(S): Five pronuclear embryos were thawed; two embryos survived, cleaved, and were transferred on day 2. A singleton term pregnancy was achieved with the delivery of a healthy boy. CONCLUSION(S): A healthy live birth was documented after uterine transfer of pronuclear stage cryopreserved (slow freeze)-thawed embryos that were in storage for 19 years and 7 months. To our knowledge this case represents the "oldest" cryopreserved human embryos resulting in a live birth to date.

Pubertal development of the first cohort of young adults conceived by in vitro fertilization in the United States.

OBJECTIVE: To characterize pubertal development of the first generation of young adults born as a result of in vitro fertilization (IVF). Demographic, clinical, and body size characteristics were examined regarding developmental milestones. DESIGN: Cross-sectional. SETTING: Academic center. PATIENT(S): Young adults (18-26 years) conceived by IVF (no gamete/embryo manipulation) 1981-1990. INTERVENTION(S): Self-administered questionnaire. MAIN OUTCOME MEASURE(S): Age at puberty onset, body size. RESULT(S): Of 560 eligible young adults, 173 completed the survey (response rate 30.9%). We analyzed data on 166 respondents (71 male and 95 female). No cases of delayed or precocious puberty were observed in the study sample. As expected, age at puberty onset was significantly higher among male subjects (12.3 years) compared with female subjects (11.5 years). A few developmental milestones were predicted by maternal age and infertility diagnoses. For both genders, a direct association was noted between age at puberty onset and height achieved in young adulthood. Structural equation models suggested an inverse relationship of female gender with age at puberty onset and body mass index. CONCLUSION(S): In vitro fertilization-conceived young adults did not exhibit pubertal abnormalities. Female gender and age at puberty onset independently predicted body mass index of IVF offspring in young adulthood.

Anti-Müllerian hormone serum levels predict response to controlled ovarian hyperstimulation but not embryo quality or pregnancy outcome in oocyte donation.

The objective of this retrospective cross-sectional study was to evaluate the value of basal serum anti-Müllerian hormone (AMH) levels as a predictor of ovarian response and pregnancy outcome in a donor egg program. The study showed that AMH was superior to other biomarkers of ovarian reserve in predicting low and high response in young women selected as oocyte donors, but that it was not predictive of embryo morphology or pregnancy outcome in the recipient population.