Effects of parity on preterm delivery in twin gestations conceived with in vitro fertilization.

Objective: To determine the relationship between prior obstetrical history and gestational age at delivery in a twin pregnancy. Design: Retrospective cohort study using the United States Society for Assisted Reproductive Technology Clinic Outcomes Reporting System database. Setting: Clinic-based data. Patients: Patients undergoing in vitro fertilization (IVF) in the United States with live delivery of twins. Interventions: None. Main outcome measures: The main outcome measures are median gestational age at delivery and rate of preterm delivery (before 37 weeks). Results: The median gestational age at delivery of IVF-conceived twins was 36.3 (interquartile rate 34.4, 37.6) weeks for nulliparous women, 35.9 (34.0, 37.1) weeks for parous women with a prior preterm birth, and 36.7 (35.1, 37.7) weeks for parous women without a prior preterm birth. The rate of preterm delivery was 61% for nulliparous women, 70% for parous women with a prior preterm birth, and 55% for parous women without a prior preterm birth. Conclusions: Parous women without a history of preterm delivery had lower rates of preterm delivery in a subsequent twin pregnancy than nulliparous women. Nulliparous women had lower rates of preterm delivery compared with parous women with a history of preterm delivery.

Public attitudes in the United States toward insurance coverage for in vitro fertilization and the provision of infertility services to lower income patients.

Objective: To assess attitudes and factors that influence public opinion in the general US population toward insurance coverage and provision of infertility care to lower income patients. Design: Cross-sectional survey. Setting: Online. Patients: A nationally representative sample of US residents. Interventions: Questionnaire with multiple choice and open response questions. Main Outcome Measures: Public attitudes toward in vitro fertilization and infertility care coverage for lower income patients. Results: A total of 1,027 (90.2%) participants completed the survey, among whom 620 (60.4%) had private insurance, 275 (26.8%) had Medicare/Medicaid, and 56 (5.5%) were uninsured. The majority (916, 89.2%) did not consider infertility a disease. Over half of the respondents (568, 55.3%) supported private insurance coverage of infertility services, including for in vitro fertilization. Most respondents, 735 (71.6%) believed that the prevalence and psychosocial impact of infertility were equal among the lower and higher income people. The majority of respondents with an opinion (512, 67.6%) believed that doctors should provide infertility treatments regardless of the income level of the patients. Of supporters, 40.1% believed in the right to have a family regardless of income, and 38.2% believed that doctors had a social responsibility to provide infertility services. After adjusting for covariates, age <45 years, noncollege graduates, desiring more children, believing that infertility was a disease, and residence in the Northeast region remained significant predictors for support of private insurance coverage. Conclusions: Public perception of infertility as a disease is one of the strongest predictors of support for insurance coverage for infertility services, underscoring the need for enhanced advocacy and education in the general public.

Provision of infertility care for the underserved in reproductive endocrinology and infertility practices associated with obstetrics and gynecology residency training programs in the United States.

Objective: To survey practice patterns designed to increase access to infertility care and evaluate the exposure of obstetrics and gynecology residents to infertility care for the underserved. Design: Cross-sectional. Setting: Reproductive endocrinology and infertility (REI) practices associated with Accreditation Council for Graduate Medical Education-accredited obstetrics and gynecology residency training programs. Patients: None. Interventions: Questionnaire survey. Main Outcome Measures: Presence of clinical programs designed to improve access to REI care, resident involvement in such programs, and perceived barriers to expanding access to care. Results: Clinical initiatives to expand access included discounted infertility services (38%, n = 30), utilization of a low-cost in vitro fertilization (IVF) program (28%, n = 22), and utilization of a resident- and/or fellow-staffed clinic to provide infertility care (39%, n = 31). The most commonly discounted infertility services were IVF (73%, n = 22), clinical consultation (70%, n = 21), and intrauterine insemination (53%, n = 16). The provision of discounted prices was correlated with the increasing practice size (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.23-4.24) and number of assisted reproductive technology cycles performed annually (OR, 3.65; 95% CI, 1.48-9.02). Academic REI practices (OR, 3.6; 95% CI, 0.98-13.25) were more likely to have a low-cost IVF program. Less than half of obstetrics and gynecology residency programs (39%, n = 31) had an associated REI clinic in which obstetrics and gynecology residents provide direct infertility care to the medically underserved. Frequency and services offered in trainee clinics varied. Multiple barriers to expanding access to care were reported. Conclusions: Reproductive endocrinology and infertility practices associated with obstetrics and gynecology residency programs utilize a diverse range of approaches to provide infertility care to the underserved in the backdrop of considerable challenges and barriers, but significant gaps persist.

Embryo morphology and live birth in the United States.

Objective: To determine the best-fit live birth rate per embryo based on maternal age, embryo stage, and embryo morphology. Design: Retrospective data analysis. Setting: Fertility clinics. Patients: The patients included were treated with in vitro fertilization in the United States at clinics reporting data to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. We analyzed live birth data of unbiopsied autologous cleavage and blastocyst stage embryos for cycles started from 2016 through 2018. The analysis included 223,377 embryo transfers with a total of 336,888 embryos. Interventions: None. Main Outcome Measures: Live birth rate per embryo and rate of multiple gestations per pregnancy. Results: At the mean maternal age of 34 years, fresh embryos produced live birth rates of 19%, 38%, 26%, and 27% for embryos aged 3, 5, 6, and 7 days, respectively. At the age 34 years, live birth rates for day 5 fresh embryos by overall morphology grade were 43% for good, 30% for fair, and 21% for poor. For the transfer of 2 fresh day 5 blastocysts, the rate of multiple gestations per pregnancy was 47% at 25 years old, 44% at 30 years old, 35% at 35 years old, and 23% at 40 years old. Conclusions: The analysis of pregnancy data in the Society for Assisted Reproductive Technology database can be used to calculate live birth rates per embryo based on maternal age, embryo age, and morphology. This information can be used for evidence-based decision making, quality control, and planning multicenter studies.

Effect of trophectoderm biopsy for PGT-A on live birth rate per embryo in good prognosis patients.

PURPOSE: To determine if blastocyst trophectoderm biopsy for PGT-A is associated with an increased rate of live birth per embryo in good prognosis IVF patients at a single center. METHODS: We performed a retrospective cohort study of good prognosis embryo transfer cycles at a single center from 1/1/2017 to 12/31/2019. We evaluated the rate of live birth per embryo with and without PGT-A for transfer of embryos in two groups of good prognosis patients: embryos from donor oocytes and embryos from autologous oocytes with maternal age less than 35 years at oocyte retrieval. Two-sided Fisher's exact tests were used for comparisons between groups. RESULTS: After transfer of embryos created from donor oocytes the live birth rate per euploid embryo was 70.6% (24/34) compared to 34.3% (35/102) for untested embryos for a rate difference of 36.3% (95% CI 18.4-54.1%, p < 0.01). After transfer of embryos created from autologous oocytes with maternal age less than 35 years at oocyte retrieval the live birth rate per euploid embryo was 70.0% (49/70) compared to 52.5% (53/101) for untested embryos for a rate difference of 17.5% (95% CI 3.0-32.0%, p = 0.03). CONCLUSIONS: In good prognosis patients at our center the live birth rate per euploid blastocyst was higher than for untested blastocysts.

Association between hospital treatment volume and major complications in ovarian hyperstimulation syndrome.

OBJECTIVE: An inverse relationship between hospital volume and adverse patient outcomes has been established for many conditions, but has not yet been examined in ovarian hyperstimulation syndrome (OHSS). Given the rarity of severe OHSS, but potential for high morbidity, this study aimed to elucidate the effect of hospital volume on inpatient OHSS-related complications. METHODS: This is a retrospective observational study querying the National Inpatient Sample, 1/2001-12/2011. Study population was 11,878 patients with OHSS treated at 735 hospitals. Annualized hospital OHSS treatment volume was grouped as: low-volume (1 case/year), mid-volume (>1 but < 3.5 cases/year), and high-volume (≥3.5 cases/year). Main outcome measure was major complication rates stratified by hospital treatment volume, assessed by multinomial regression and binary logistic regression models. RESULTS: A total of 2,415 (20.3%) patients were treated at low-volume centers, 5,023 (42.3%) at mid-volume centers, and 4,440 (37.4%) at high-volume centers. Patients treated at high-volume centers were more likely to be older and less comorbid with higher incomes and lower body mass index (P < 0.05). High-volume hospitals were more likely to be urban-teaching centers with large bed capacity (P < 0.001). Overall, 1,624 (13.7%) patients experienced a major complication during hospitalization. Patients treated at high-volume hospitals had lower rates of major complications (high: 11.0%, mid: 15.2%, low: 15.6%, P < 0.001). On multivariable analysis, treatment at high-volume hospitals was independently associated with a nearly 20% lower rate of major complications (odds ratio 0.82, 95% confidence interval 0.70-0.97, P = 0.021). CONCLUSION: Our study suggests that higher hospital treatment volume for OHSS may be associated with improved outcomes.

The influence of obesity on incidence of complications in patients hospitalized with ovarian hyperstimulation syndrome.

OBJECTIVE: To study the impact of body habitus on risk of complications resulting from ovarian hyperstimulation syndrome (OHSS) in hospitalized patients. METHODS: This is a retrospective observational study examining the National Inpatient Sample between January 2012 and September 2015. Patients were women < 50 years of age diagnosed with OHSS, classified as non-obese, class I-II obesity, or class III obesity. Intervention included multinomial logistic regression to identify factors associated with obesity and binary logistic regression for independent risk factors for complications. Main outcome measures were incidence of (i) any or (ii) multiple complication(s). RESULTS: Of 2745 women hospitalized with OHSS, 2440 (88.9%) were non-obese, 155 (5.6%) had class I-II obesity, and 150 (5.5%) had class III obesity. Obese women (either class I-II or III) had a higher degree of comorbidity, had lower incomes, and were less likely to have private insurance than non-obese women (all P < 0.001). Obese women had lower rates of OHSS-related complications than non-obese women (any complication: non-obese 65.2%, class I-II 54.8%, and class III 46.7%, P < 0.001; and multiple complications: non-obese 38.5%, class I-II 32.3%, and class III 20.0%, P < 0.001). In the multivariable model, obesity remained independently associated with a decreased risk of complications (class I-II odds ratio 0.57, 95% confidence interval 0.39-0.83, P = 0.003; class III odds ratio 0.30, 95% confidence interval 0.20-0.44, P < 0.001). Obese women were also less likely to require paracentesis (non-obese 32.8%, class I-II 9.7%, and class III 13.3%, P < 0.001). CONCLUSION: Our study suggests that obesity is associated with decreased OHSS-related complication rates in hospitalized patients.

Making it (net)work: a social network analysis of "fertility" in Twitter before and during the COVID-19 pandemic.

OBJECTIVE: To characterize activity, text sentiment, and online community characteristics regarding "fertility" on Twitter before and during the COVID-19 pandemic using social network analysis. DESIGN: Cross-sectional analysis. SETTING: Publicly available Twitter data. PATIENTS: Not applicable. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Number of users (vertices); edges (connections, defined as unique and total); self-loops (tweet without connection to another user); connected components (groups of users communicating back and forth frequently); maximum vertices in a connected component (largest group size); maximum and average geodesic distance (number of tweets to connect two users in the network); graph density; positive and negative sentiment tweets; and top 5 hashtags and top 5 word pairs. RESULTS: There were 1426 unique users and 401 groups in the pre-COVID-19 data compared to 1492 unique users and 453 groups in the during COVID-19 data. There was no difference in the number of total connections (96.8% [1381/1426] vs. 96.0% [1433/1492]) or self-loops (20.0% [286/1426] vs. 22.1% [329/1492]) before and during the COVID-19 pandemic. The percentage of unique connections per user decreased during COVID-19 (91.6% [1381/1508] pre-COVID-19 vs. 83.3% [1433/1720] during COVID-19). The average and maximum distance between users in the community increased during COVID-19 (maximum: 5 pre-COVID-19, 8 during COVID-19; average 1.95 pre-COVID-19, 2.43 during COVID-19). The percentage of positive sentiments per total number of tweets increased during COVID-19 (58.1% pre-COVID-19 [773/1331] vs. 64.3% [1198/1863] during COVID-19). The top 5 hashtags changed during COVID-19 to include COVID-19. The top word pairs changed from "family, hereditary; parents, children" to "fertility, treatment; healthcare, decisions." CONCLUSIONS: Despite the challenge to the fertility community amidst the COVID-19 pandemic, the overall Twitter sentiment regarding fertility was more positive during than before the pandemic. Top hashtags and word pairs changed to reflect the emergence of COVID-19 and the unique healthcare decision-making challenges faced. While the character, the number of users, and the total connections remained constant, the number of unique connections and the distance between users changed to reflect more self-broadcasting and less tight connections.

Does timing matter when initiating elagolix in a natural menstrual cycle?

OBJECTIVE: To investigate the efficacy of elagolix when administered at different time points in a menstrual cycle. DESIGN: Clinical case series. SETTING: Academic reproductive endocrinology center. PATIENTS: Ovulatory women not desiring pregnancy. INTERVENTIONS: Six doses of elagolix 200 mg were administered over 4 days, starting at 3 different points in a menstrual cycle: early follicular; late follicular; and midluteal. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P) concentrations were measured at baseline, during elagolix administration, and 1 day after the last dose. Transvaginal ultrasounds were performed to monitor follicle sizes. MAIN OUTCOME MEASURES: Serum FSH, LH, E2, and P. RESULTS: Twelve women, four per group, completed the study. Subjects were 23-42 years of age. Demographics and ovarian reserve parameters were similar among participants. Elagolix suppressed FSH, LH, E2, and P when administered in the early follicular and midluteal phases but had mixed results when administered in the late follicular phase. Two participants demonstrated suppression of all four hormones. One participant ovulated, indicated by an increase in P concentration and development of a corpus luteum. A second participant did not ovulate yet demonstrated an increase in E2 concentration with growth of a dominant follicle. There were no significant differences in median percent change of hormone concentrations across study groups. CONCLUSIONS: The results of this study suggest that elagolix can suppress the hypothalamic-pituitary-ovarian axis when initiated at different points in a menstrual cycle. Optimal dosing and treatment window for consistent hormone suppression have yet to be determined. CLINICAL REGISTRATION NUMBER: NCT04060992.

Association of bioavailable inhibin B and oocyte yield in controlled ovarian stimulation.

OBJECTIVE: To determine if the biologically active or bioavailable inhibin B (bio-inhB) correlated with the oocyte yield in controlled ovarian stimulation (COS). DESIGN: Cross-sectional study. SETTING: Academic center. PATIENTS: Women undergoing oocyte cryopreservation. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Serum of women were sampled to measure bio-inhB at three points: baseline ("start"); middle ("mid"); and end of COS. A validated, highly specific enzyme-linked immunosorbent assay (Ansh Labs, Webster, TX) measured bio-inhB. The Spearman tests analyzed correlations between bio-inhB and other ovarian reserve markers, including age, follicle-stimulating hormone (FSH), antral follicle count (AFC), and antimüllerian hormone (AMH), and correlations between these markers and oocyte yield. RESULTS: A total of 144 women were included. Bioavailable inhibin B at the mid and end of COS, plus its delta, were strongly correlated with other ovarian reserve markers. As the bio-inhB concentration increased, the AFC and AMH levels also increased, whereas the FSH concentration and age decreased. Bioavailable inhibin B values, except at the start of COS, were more strongly correlated with oocyte yield than the FSH concentration (r = 0.72-0.82 vs. r = -0.44) and correlated similarly to the AFC and AMH concentration (r = 0.79 and 0.81, respectively). These correlations strengthened in those with diminished ovarian reserve, specifically age ≥35 years or AMH concentration <2 ng/mL (r = 0.71-0.86 vs. r = 0.49-0.67). CONCLUSIONS: Predicting COS outcome is imperfect. When using a highly specific enzyme-linked immunosorbent assay, bio-inhB correlated with the oocyte yield similar to or more strongly than traditionally used ovarian reserve markers. These correlations strengthened in cases of diminished ovarian reserve. Bioavailable inhibin B provides physicians with an additional clinical tool for estimating COS outcome.

Developmental potential of immature human oocytes aspirated after controlled ovarian stimulation.

PURPOSE: Intracytoplasmic sperm injection (ICSI) for initially immature oocytes that mature in vitro is controversial and practice varies widely. While it may increase the number of usable embryos, it may also be time-intensive and potentially low-yield. This study sought to elucidate which patients may benefit from ICSI of initially immature oocytes that matured in vitro. METHODS: A retrospective study comparing fertilization, cleavage, blastulation, and embryo usage rates between sibling initially immature and mature oocytes that underwent ICSI between 2015 and 2019 was performed. Outcomes of initially immature oocytes were stratified by initial maturation stage, timing of progression to metaphase II (MII) in vitro, percentage of mature oocytes in the cycle, and female age. RESULTS: Ten thousand eight hundred seventeen oocytes from 889 cycles were included. Of 3137 (29.0%) initially immature oocytes, 418 (13.3%) reached MII later on the day of retrieval (day 0) and 1493 (47.6%) on day 1. Overall, embryos originating from initially immature oocytes had lower cleavage and blastulation rates compared to those from initially mature oocytes (P<0.05, all groups). However, embryos from oocytes that matured later on day 0 comprised a unique subset that had clinically similar cleavage (75% vs 80%, RR 0.93, P=0.047) and blastulation rates (41% vs 50%, RR 0.81, P=0.024) compared to initially mature oocytes. Women with low percentages of mature oocytes in the cycle overall and women ≥40 in cleavage cycles derived the highest relative benefit from the use of immature oocytes. CONCLUSION: ICSI of immature oocytes, particularly those that mature later on the day of retrieval, may improve numbers of usable embryos. This study supports routine reassessment of immature oocytes for progression to MII and ICSI on day 0. An additional reassessment on day 1 may also be of use in older women or those with low percentage of mature oocytes.

What is the optimal timing of intracytoplasmic sperm injection (ICSI) after EGG retrieval? A randomized controlled trial.

PURPOSE: To determine if oocyte denudation and ICSI at 36.5 versus 39 h post HCG and/or Lupron trigger (2.5 h versus 5 h post-oocyte retrieval) influences fertilization and blastulation rates in good prognosis couples METHODS: We performed a prospective, randomized controlled trial of 12 patients undergoing IVF with ICSI at an academic fertility center, resulting in 206 MII oocytes analyzed. At time of retrieval, patients with more than 10 oocytes retrieved had their oocytes randomized into two groups-one group for oocyte denudation and ICSI at 36.5 h post HCG and/or Lupron trigger and the other group for these procedures at 39 h post HCG and/or Lupron trigger (2.5 and 5 h after oocyte retrieval). Primary outcomes were fertilization and blastulation rates. RESULTS: No difference was observed in fertilization rate, total blastulation rate, or day of blastulation based on timing of denudation and ICSI (all p > 0.05). Multiple regression analyses for fertilization and blastulation controlling for age and BMI revealed no difference in fertilization based on time of ICSI (p = 0.38, 0.71, respectively). A conditional logistic regression to account for multiple oocytes derived from each patient also found no difference in fertilization or blastulation based on timing of ICSI, even when controlling for age and BMI (p = 0.47, 0.59, respectively). CONCLUSION(S): In good prognosis couples, we observed no difference in fertilization or blastulation rates based on timing of ICSI within the currently accepted 2- to 6-h window post-retrieval based on a 34-h trigger. The oocyte appears to have a physiological tolerance for fertilization during this window of time, and variability in the timing of ICSI during this window is unlikely to have an impact on cycle outcome.

A validated model for predicting live birth after embryo transfer.

Accurately predicting the probability of live birth and multiple gestations is important for determining a safe number of embryos to transfer after in vitro fertilization. We developed a model that can be fit to individual clinic data for predicting singleton, twin, and total live birth rates after human embryo transfer. The predicted and observed rates of singleton and twin deliveries were compared in a tenfold cross-validation study using data from a single clinic. The model presented accounts for patient age, embryo stage (cleavage or blastocyst), type of transfer cycle (fresh or frozen) and uterine/universal factors. The standardized errors for rates of singleton and twin deliveries were normally distributed and the mean errors were not significantly different from zero (all p > 0.05). The live birth rates per embryo varied from as high as 43% for fresh blastocysts in the 35-year-old age group to as low as 1% for frozen cleavage stage embryos in the 43-year-old age group. This quantitative model or a simplified version can be used for clinics to generate and analyze their own data to guide the number of embryos to transfer to limit the risk of multiple gestations.

Long-term imatinib diminishes ovarian reserve and impacts embryo quality.

PURPOSE: Tyrosine kinase inhibitors (TKIs) such as imatinib are commonly used chemotherapeutics, but the effects of long-term treatments on reproductive outlook for cancer survivors are unknown. The purpose of this study was to examine the effects of long-term imatinib treatments on follicle development and embryo quality. Since prospective studies are not possible in healthy humans, we have incorporated a commonly used mouse model. METHODS: Adult female mice were treated with daily IP injections of imatinib for 4-6 weeks. Liquid chromatography-mass spectrometry was used to measure imatinib in serum and ovarian tissues. At the end of treatments, females were superovulated and mated to yield fertilized embryos. Oocytes and embryos were collected from oviducts, assessed for development by microscopy, and fertilized embryos were cultured in vitro. Blastocysts were fixed and stained for differential cell counts. RESULTS: Long-term imatinib treatments caused a shift in follicle development, with imatinib-treated females having fewer primordial follicles, but an increase in primary and secondary follicles (P < 0.05). There was no effect on ovulation or fertilization rates. However, blastocysts from imatinib-treated females had fewer total cells (P < 0.05) and a significant shift from inner cell mass to increased trophectoderm cells. CONCLUSION: This pilot study indicates that long-term TKI treatments may have significant impact on ovarian reserve and embryo developmental capacity. More studies are needed in other model systems to determine the long-term impact of TKIs in patients. Knowing the potential effects of chemotherapeutics on reproductive outlook is critical for quality of life and more research is needed.

Pushing the limits of detection: investigation of cell-free DNA for aneuploidy screening in embryos.

OBJECTIVE: To determine the accuracy of cell-free DNA (cfDNA) in spent embryo medium (SEM) for ploidy and sex detection at the cleavage and blastocyst stages. To determine if assisted hatching (AH) and morphologic grade influence cfDNA concentration and accuracy. DESIGN: Prospective cohort. SETTING: Academic fertility center. PATIENT(S): Nine patients undergoing IVF; 41 donated two-pronuclei embryos and 20 embryos from patients undergoing preimplantation genetic testing for aneuploidy (PGT-A). INTERVENTIONS(S): In a donated embryo arm, SEM was collected on days 3 and 5, with one-half of the embryos undergoing AH before and one-half after. In a clinical arm, SEM was collected on day 5 before trophectoderm (TE) biopsy. Samples underwent PGT-A with the use of next-generation sequencing. cfDNA results were compared with corresponding whole embryos and TE biopsies. MAIN OUTCOME MEASURE(S): Concordance rates, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for ploidy and sex detection with the use of cfDNA. RESULT(S): Of 141 samples, cfDNA was amplified in 39% and 80.4% of days 3 and 5 SEM, respectively. Concordances for ploidy and sex, respectively, were 56.3% and 81.3% between day 3 cfDNA and whole embryos, and 65% and 70% between day 5 cfDNA and TE biopsies. Day 5 cfDNA sensitivity and specificity for aneuploidy were 0.8 and 0.61, respectively. PPV and NPV were 0.47 and 0.88, respectively. Timing of AH and morphology did not influence cfDNA concentration or accuracy. CONCLUSION(S): cfDNA is detectable on days 3 and 5, but more accurate on day 5. Although our data suggest moderate concordance rates, PGT-A with the use of cfDNA must be further optimized before clinical implementation.

Blastulation timing is associated with differential mitochondrial content in euploid embryos.

PURPOSE: Preimplantation genetic screening (PGS) and assessment of mitochondrial content (MC) are current methods for selection of the best embryos for transfer. Studies suggest that time-lapse morphokinetics (TLM) may also be helpful for selecting embryos more likely to implant. In our study, we sought to examine the relationship between TLM parameters and MC to determine if they could be used adjunctively in embryo selection. We also examined the relationship between MC with ploidy and blastulation. METHODS: Cryopreserved human embryos at the zygote stage were thawed and cultured in a time-lapse system. Blastomere and trophectoderm biopsies were performed on days 3 and 6. Biopsied cells and all whole embryos from day 6 were analyzed for MC (ratio of mitochondrial to nuclear DNA) and ploidy using next-generation sequencing. RESULTS: In embryos, MC per cell declined between day 3 and day 6. While early cleavage parameters did not predict MC, embryos with longer blastulation timing had higher MC on day 6. Day 6 MC was lower in euploid vs. aneuploid embryos and lower in blastocysts vs. arrested embryos. CONCLUSIONS: A lower MC at the blastocyst stage was associated with euploid status and blastocyst formation, indicating better embryo quality compared to those with a higher MC. Higher MC in aneuploid and arrested embryos may be explained by slower cell division or degradation of genomic DNA over time. Blastulation timing may be helpful for selection of higher quality embryos. Combining blastulation timing and MC along with morphologic grading and euploid status may offer a new direction in embryo selection.

Clomiphene Stair-Step Protocol for Women With Polycystic Ovary Syndrome.

OBJECTIVE: To compare time to ovulation, ovulation rates, and side effect profile of traditional and the stair-step protocol for ovulation induction using clomiphene citrate in women with polycystic ovary syndrome (PCOS). METHODS: We performed a retrospective study of women seeking care for infertility with a diagnosis of PCOS at a university-based infertility clinic from July 2012 to July 2014. We included patients who were resistant to the initial starting dose of 50 mg clomiphene. The primary outcome was time to ovulation. Secondary outcomes included ovulation rates, clinical pregnancy rates, and mild and moderate-to-severe side effects based on dose. For the traditional protocol, higher doses of clomiphene were used each subsequent month if no ovulation occurred. For the stair-step protocol, higher doses of clomiphene were given 7 days after the last dose if no dominant follicles were seen on ultrasonography. Our study had 80% power to detect a 20% difference in ovulation. RESULTS: One hundred nine patients were included in the analysis with 66 (60.6%) in the traditional and 43 (39.4%) in the stair-step protocol. Age and body mass index were similar between groups. The time to ovulation was decreased in the stair-step protocol group compared with the traditional protocol group (23.1±0.9 days vs 47.5±6.3 days). Ovulation rates were increased in the stair-step group compared with the traditional group at 150 mg (16 [37%] vs 8 [12%], P=.004) and at 200 mg (9 [21%] vs 3 [5%], P=.01). Pregnancy rates were similar between groups once ovulation was achieved (12 [18.1%] vs 7 [16.3%], P=.08). The stair-step protocol had an increased incidence of mild side effects (vasomotor flushes, headaches, gastrointestinal disturbance, mastalgia, changes in mood; 18 [41%] vs 8 [12%]), but there was no difference in the incidence of severe side effects (headaches, visual disturbances). CONCLUSION: For women with PCOS, the stair-step clomiphene protocol is associated with decreased time to ovulation and increased ovulation rates at higher doses when compared with the traditional protocol.

Demographic analysis of a low resource, socioculturally diverse urban community presenting for infertility care in a United States public hospital.

BACKGROUND: Infertility is a prevalent disease of reproductive health that exerts an impact on an estimated 80 million people worldwide. For many, involuntary childlessness becomes a central and preoccupying issue in their lives, the impact of which is exacerbated by lack of access to basic care and treatment. These effects maybe further magnified among immigrant communities, a growing but highly marginalized population that has been shown in other areas of reproductive health to experience worse health outcomes and delays in access to care. To date, few studies have examined the unique medical and sociocultural considerations of infertility among immigrant populations in the United States. METHODS: Our study is a cross-sectional analysis of women presenting for infertility evaluation at a county hospital serving a low resource, socioculturally diverse largely immigrant communities in comparison to infertile women from a largely affluent population presenting to a high resource, comprehensive fertility center. We employed surveys to evaluate demographics and socioeconomic parameters as well as abstracted data from medical records to obtain infertility diagnoses. Multivariate regression analysis was applied to examine impact of sociocultural factors as predictors of duration of untreated infertility disease burden experienced by patients. RESULTS: Eighty-seven women were included in our analysis. In the county hospital/low resource clinic (LR), the mean age was 32.9 ± 4.9 vs 36.4 ± 6.3 years in the fee-for-service/high resource clinic (HR). The mean reported duration of infertility in LR and HR patients was 3.4 ± 3.0 vs 2.3 ± 1.5 years. 70% of LR patients were monolingual non-English speakers vs 5.4% of HR patients. 59% of LR patients reported an annual household income of less than $25,000 and 70% did not have a college degree. 81.1% of HR patients reported an income of higher than $100,000, and 81.1% had completed college or graduate school. The most common infertility diagnosis in the LR was anovulation (38%) and tubal factor (28%) compared to diminished ovarian reserve (37.8%) and male factor (51.4%) in the HR. After controlling for age at the initiation of pregnancy attempt, lower education level, lower income, and immigrant status were significantly correlated with a longer duration of infertility. CONCLUSIONS: Women presenting for infertility care to a low resource county medical center represent immigrant communities and are generally of younger age, but with a longer duration of infertility. This study identifies lower educational level, income, and immigrant status as barriers in access to care.

Modified natural cycle in in vitro fertilization.

The first live birth after IVF was achieved in a purely natural cycle. Because early attempts at IVF were associated with low efficiency, ovarian stimulation was added to achieve a greater margin for error in oocyte retrieval, fertilization, and thus, overall pregnancy success. As technology improved, the intuitive appeal of the natural cycle led investigators to once again attempt IVF without antecedent gonadotropin stimulation. Triggering of ovulation with hCG was added to allow for accurate scheduling of oocyte retrieval and thus increased oocyte yield. When GnRH antagonists became available, premature ovulations could be prevented, albeit at the cost of adding some form of ovarian stimulation to continue follicle development until ovulation triggering. This type of cycle came to be known as the "modified natural cycle." These modified natural IVF cycles are associated with decreased medication costs, they produce acceptable pregnancy rates, and they may be particularly appropriate for patients at increased risk of ovarian hyperstimulation syndrome, poor responders, and those wishing to avoid supernumerary embryo production.

A comparison of live birth rates and perinatal outcomes between cryopreserved oocytes and cryopreserved embryos.

PURPOSE: Prior studies suggest that pregnancy outcomes after autologous oocyte cryopreservation are similar to fresh in vitro fertilization (IVF) cycles. It is unknown whether there are differences in pregnancy and perinatal outcomes between cryopreserved oocytes and cryopreserved embryos. METHODS: This is a retrospective cohort study comparing pregnancy and perinatal outcomes between oocyte and embryo cryopreservation at a university-based fertility center. We included 42 patients and 68 embryo transfers in patients who underwent embryo transfer after elective oocyte preservation (frozen oocyte-derived embryo transfer (FOET)) from 2005 to 2015. We compared this group to 286 patients and 446 cycles in women undergoing cryopreserved embryo transfer (frozen embryo transfer (FET)) from 2012 to 2015. RESULTS: Five hundred fourteen transfer cycles were included in our analysis. The mean age was lower in the FOET vs FET group (34.3 vs 36.0 years), but there were no differences in ovarian reserve markers. Thawed oocytes had lower survival than embryos (79.1 vs 90.1%); however, fertilization rates were similar (76.2 vs 72.8%). In the FOET vs FET groups, clinical pregnancies were 26.5 and 30%, and live birth rates were 25 and 25.1%. Miscarriages were higher in the FET group, 8.1 vs 1.5%. There were no differences in perinatal outcomes between the two groups. The mean gestational age at delivery was 39.1 vs 38.6 weeks, mean birth weight 3284.2 vs 3161.1 gms, preterm gestation rate 5.9 vs 13.4%, and multiple gestation rate 5.9 vs 11.6%. CONCLUSIONS: In our study, live birth rates and perinatal outcomes were not significantly different in patients after oocyte and embryo cryopreservation.