Meeting the demand for fertility services: the present and future of reproductive endocrinology and infertility in the United States.

The field of reproductive endocrinology and infertility (REI) is at a crossroads; there is a mismatch between demand for reproductive endocrinology, infertility and assisted reproductive technology (ART) services, and availability of care. This document's focus is to provide data justifying the critical need for increased provision of fertility services in the United States now and into the future, offer approaches to rectify the developing physician shortage problem, and suggest a framework for the discussion on how to meet that increase in demand. The Society of REI recommend the following: 1. Our field should aggressively explore and implement courses of action to increase the number of qualified, highly trained REI physicians trained annually. We recommend efforts to increase the number of REI fellowships and the size complement of existing fellowships be prioritized where possible. These courses of action include: a. Increase the number of REI fellowship training programs. b. Increase the number of fellows trained at current REI fellowship programs. c. The pros and cons of a 2-year focused clinical fellowship track for fellows interested primarily in ART practice were extensively explored. We do not recommend shortening the REI fellowship to 2 years at this time, because efforts should be focused on increasing the number of fellowship training slots (1a and b). 2. It is recommended that the field aggressively implements courses of action to increase the number of and appropriate usage of non-REI providers to increase clinical efficiency under appropriate board-certified REI physician supervision. 3. Automating processes through technologic improvements can free providers at all levels to practice at the top of their license.

Black race associated with lower live birth rate in frozen-thawed blastocyst transfer cycles: an analysis of 7,002 Society for Assisted Reproductive Technology frozen-thawed blastocyst transfer cycles.

OBJECTIVE: To evaluate if racial/ethnic differences in pregnancy outcomes persisted in frozen-thawed embryo transfer (FET) cycles on a national level. DESIGN: Retrospective cohort study. SETTING: Clinic-based data. PATIENT(S): A total of 189,000 Society for Assisted Reproductive Technology FET cycles from 2014-2016 were screened, of which 12,000 cycles had available fresh cycle linkage information and ultimately, because of missing data, 7,002 FET cycles were included. Cycles were stratified by race (White, Black, Asian, and Hispanic). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was live birth rate. Secondary outcomes were implantation rate, clinical pregnancy rate, multiple pregnancy rate, and clinical loss rate (CLR). RESULT(S): Live birth rate was significantly lower in the Black vs. White and Asian, but not Hispanic group. Implantation rate was also significantly lower and CLR higher in the Black group compared with all other groups (all P<.01). Black women had a lower risk of live birth (adjusted risk ratio, 0.82; 95% confidence interval [CI], 0.73-0.92) and a higher risk of clinical loss (adjusted risk ratio, 1.59; 95% CI, 1.28-1.99) compared with White women. There was no significant difference between groups in clinical pregnancy rate or multiple pregnancy rate. When the analysis was limited to preimplantation genetic testing FET cycles, there remained a significantly lower implantation rate in the Black group compared with all other groups (all P<.01). CONCLUSION(S): Black race remains an independent predictor of reduced live birth rate in FET cycles, likely because of higher CLR.

The effect of rapid and delayed insemination on reproductive outcome in conventional insemination and intracytoplasmic sperm injection in vitro fertilization cycles.

PURPOSE: The precise timing of insemination after oocyte retrieval is sometimes challenging. In this study, we have assessed the effect of the variation in insemination timing on reproductive outcome for both conventional insemination (CI) and intracytoplasmic sperm injection (ICSI) cycles. METHODS: A single-center retrospective cohort data analysis was performed on 6559 patients (9575 oocyte retrievals) from January 2017 to July 2019. The main outcome measured was live birth rates. Secondary outcomes included fertilization rate per all oocytes retrieved, blastocyst utilization, clinical pregnancy, and miscarriage rates. The time interval between oocyte retrieval and insemination was analyzed in eight categories: 0 (0- < 0.5 h), 1 (0.5- < 1.5 h), 2 (1.5- < 2.5 h), 3 (2.5- < 3.5 h), 4 (3.5- < 4.5), 5 (4.5- < 5.5), 6 (5.5-6.5), and 7 (6.5- < 8 h). The number of retrievals in each group (0-7) was 586, 1594, 1644, 1796, 1836, 1351, 641, and 127 respectively. RESULTS: The mean fertilization rate for CI ranged from 54.1 to 64.9% with a significant difference between time categories 0 and 5 (p < 0.001) and 1 and 5 (p < 0.0.001). The mean fertilization rate for ICSI ranged from 52.8 to 67.3% with no significant difference between time categories. Blastocyst rate for CI and ICSI was not significantly different. Miscarriage and clinical pregnancy rates in CI and ICSI were not significantly different. Live birth rates differed significantly (p < 0.05) in CI with time categories 0 and 7 representing the lowest rates, but not in the ICSI group. CONCLUSION: If performing CI or ICSI before 1.5 h and > 6.5 h, any detrimental effects are moderate on fertilization but do not affect blastocyst usage and birth rates. TRIAL REGISTRATION: Institutional Review Board Approval from the Beth Israel Deaconess Medical Centre [IRB Protocol #: 2015P000122].

Multiple cryopreservation-warming cycles, coupled with blastocyst biopsy, negatively affect IVF outcomes.

RESEARCH QUESTION: Do multiple cryopreservation-warming cycles, coupled with blastocyst biopsy, negatively affect IVF outcomes? DESIGN: Patients undergoing IVF with homologous single embryo transfer, and who underwent trophectoderm biopsy for preimplantation genetic testing for aneuploidy (PGT-A) between 2013 and 2017, were divided into three groups based on degree of embryonic micromanipulation: once-biopsied, once-cryopreserved (group BC, n = 2603), once-biopsied, twice-cryopreserved (group CBC, n = 95) and twice-biopsied, twice-cryopreserved (group BCBC, n = 15). The primary outcome was live birth; secondary outcomes included positive serum pregnancy test, clinical pregnancy and miscarriage. RESULTS: Group CBC had a significantly lower chance of live birth (adjusted RR 0.57, 95% CI 0.41 to 0.79) and clinical pregnancy (adjusted RR 0.67, 95% CI 0.53 to 0.85) compared with group BC. Miscarriage rates were similar between groups BC and CBC (adjusted RR 1.3, 95% CI 0.64 to 2.7). CONCLUSIONS: Multiple cryopreservation-warming cycles, coupled with blastocyst biopsy, negatively affect IVF outcomes. Although PGT-A is thought to improve reproductive outcomes on a per transfer basis, caution must be exercised in counselling patients on the possibility of diminishing returns owing to further embryonic micromanipulation after an embryo has been cryopreserved.

Association between in vitro fertilization and ischemic placental disease by gestational age.

OBJECTIVE: To evaluate the association between in vitro fertilization (IVF) and ischemic placental disease (IPD), stratified by gestational age. DESIGN: We performed a secondary analysis of a retrospective cohort study of deliveries. SETTING: Deliveries were performed over 15 years at a single tertiary hospital. PATIENT(S): We included all parturients who had a live born infant or an intrauterine fetal demise (IUFD). INTERVENTION(S): We compared pregnancies resulting from IVF cycles to non-IVF pregnancies. MAIN OUTCOME MEASURE(S): The primary outcomes were preterm and term IPD (preeclampsia, placental abruption, small-for-gestational age infant [SGA], or an intrauterine fetal demise [IUFD] due to placental insufficiency). RESULT(S): Of the 69,084 deliveries during the study period, 3,763 (5.4%) were conceived with IVF. The incidence of preterm delivery was 32.6% in IVF pregnancies and 10.8% in non-IVF pregnancies. Multiple gestations were more common in IVF pregnancies. Compared to non-IVF pregnancies, IVF pregnancies were more likely to develop both preterm and term IPD, even after adjustment for maternal age and parity. The risk of preterm IPD was 4 times higher (95% confidence interval, 3.7-4.4) in patients who underwent IVF compared with those who did not undergo IVF. Among parturients who delivered at ≥37 weeks of gestation, IVF pregnancies had 1.7 times the risk of term IPD (95% confidence interval, 1.6-1.9) compared with non-IVF pregnancies. CONCLUSION(S): IVF was strongly associated with preterm IPD. We found a similar, but attenuated, association between IVF and term IPD. The stronger association with preterm IPD suggests an association between IVF and placental insufficiency.

Assisted reproductive technology outcomes in female-to-male transgender patients compared with cisgender patients: a new frontier in reproductive medicine.

OBJECTIVE: To investigate assisted reproductive technology (ART) outcomes in a female-to-male transgender cohort and compare the results with those of a matched cisgender cohort. DESIGN: Matched retrospective cohort study. SETTING: In vitro fertilization clinic. PATIENT(S): Female-to-male transgender patients (n = 26) who sought care from 2010 to 2018. A cisgender cohort (n = 130) was matched during the same time period by age, body mass index, and antimüllerian hormone levels. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Cycle outcomes, including oocyte yield, number of mature oocytes, total gonadotropin dose, and peak E2 levels. RESULT(S): The mean number of oocytes retrieved in the transgender group was 19.9 ± 8.7 compared with 15.9 ± 9.6 in the cisgender group. Peak E2 levels were the same between the two groups. The total dose of gonadotropins used was higher in the transgender group compared with the cisgender group (3,892 IU vs. 2,599 IU). Of the 26 patients, 16 performed oocyte banking only. Seven couples had fresh or frozen transfers, with all achieving live births. CONCLUSION(S): This is the first study of this size investigating ART outcomes in female-to-male transgender patients. The findings may serve to reassure transgender patients and their care providers that outcomes can be excellent even if testosterone therapy has already been initiated. Further investigation needs to be performed on the generalizability of these findings, and whether similar results can be achieved without stopping testosterone therapy.

To test or not to test? A framework for counselling patients on preimplantation genetic testing for aneuploidy (PGT-A).

STUDY QUESTION: What is the treatment path and cumulative live birth (CLB) rate from a single oocyte retrieval of patients who intend to pursue PGT-A at the start of an IVF cycle compared to matched controls? SUMMARY ANSWER: The choice of PGT-A at the start of the first IVF cycle decreases the CLB per oocyte retrieval for patients <38 years of age, however patients ≥38 years of age benefit significantly per embryo transfer (ET) when live birth (LB) is evaluated. WHAT IS KNOWN ALREADY: PGT-A has been shown to reduce the practice of transferring multiple embryos and to confer a higher live birth rate per transfer. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study from December 2014 to September 2016, involving 600 patients: those intending PGT-A for their first IVF cycle (N = 300) and their matched controls. Post-hoc power calculations (alpha of 0.05, power of 0.80) indicated that our study was powered adequately to demonstrate significant differences in CLB per retrieval and LB per transfer. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was performed at a large academically affiliated infertility practice where approximately 80% of patients have insurance coverage for fertility care. Patients were identified through electronic medical records, and those who intended to pursue PGT-A at the start of stimulation were assessed. Patients were matched by age, time of oocyte retrieval and oocyte yield to the same number of controls. CLB outcomes per single retrieval, including the fresh and frozen transfers arising from the initial stimulation cycle, were calculated. MAIN RESULTS AND THE ROLE OF CHANCE: PGT-A was not beneficial when CLB rate was assessed per retrieval, however its benefits were significant when LB rate was assessed per transfer. First cycle, <38 year-old patients who intended to have PGT-A had a significantly (P < 0.001) lower CLB rate per oocyte retrieval compared to controls (49.4% vs. 69.1%). Conversely, patients ≥ 38 years in the PGT-A group had similar CLB rates compared to controls per oocyte retrieval, while LB rates per transfer were doubled compared to controls (62.1% vs. 31.7%; P < 0.001). Of the first-cycle PGT-A and control patients, 25.3% and 2.3% failed to achieve a transfer, respectively. LIMITATIONS, REASONS FOR CAUTION: This is not a true intention-to-treat study, due to its retrospective nature. Additionally, the number of patients with two or more previous miscarriages was significantly greater in the PGT-A group as compared to controls, however a sub-analysis showed that this failed to impact outcomes. WIDER IMPLICATIONS OF THE FINDINGS: The findings indicate that PGT-A may be detrimental for those <38 years old undergoing their first IVF cycle. PGT-A has the greatest clinical impact when a transfer is achieved in the ≥38 years old population. This study evaluates the typical treatment path following a patient's choice to pursue PGT-A at the cycle start, and can be used as a guide for counselling patients in relation to age and cycle number. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Magnetic resonance imaging performance for diagnosis of ovarian torsion in pregnant women with stimulated ovaries.

BACKGROUND: To determine if asymmetric ovarian edema on non-contrast MRI can be used to distinguish torsed from non-torsed stimulated ovaries in pregnant women. METHODS: In this retrospective study, our radiology database was searched for women who were pregnant and who had undergone ovarian stimulation and underwent MRI abdomen/pelvis from 1/2000-12/2012. At our institution, ultrasound is typically performed as a first line study for pregnant women with pelvic pain, with MR for those patients with indeterminate findings. 64 pregnant women (gestational age range 3-37 weeks) were included. MRI indication, prospective interpretation, operative diagnosis, and follow-up were recorded. Two blinded radiologists (with a third radiologist tie-breaker) independently measured and described the ovaries, including the likelihood of torsion. If one or both ovaries/adnexa had an underlying lesion such as a dermoid, cystadenoma, or abscess, the patient was excluded from size and signal intensity comparison (N = 14). For the remaining 50 women, comparison was made of the ovaries in women with normal ovaries (N = 27), stimulated ovaries without torsion (N = 11), non-stimulated ovaries with torsion (N = 3), and stimulated ovaries with torsion (N = 3). Patients with asymmetric ovarian edema without stimulation or torsion (N = 3) and with polycystic ovary syndrome (N = 3) were analyzed separately. RESULTS: Average normal ovarian length was 3.2 cm, compared to 4.5 cm for asymmetric edema and 5.6-8.8 cm for the other four groups. Average difference in greatest right and left ovarian diameter was 19% for normal ovaries compared to 24-37% for the other 5 groups. Asymmetric signal on T2-weighted imaging (T2WI) was seen in 12% (3/27) of normal ovaries compared to 9% (1/11) of stimulated patients without torsion, 33% (1/3) of patients with PCOS and 67% (2/3) of patients with torsion both without and with stimulation. The correct diagnosis of torsion was made prospectively in 5/6 cases but retrospectively in only 3/6 cases. In patients with stimulation, correct diagnosis of torsion was made in 2/3 cases prospectively (both with asymmetric T2 signal) and retrospectively in only 1/3 cases. In 13/64 patients, other acute gynecologic and non-gynecologic findings were diagnosed on MRI. CONCLUSIONS: Enlarged edematous ovary can be seen with ovarian stimulation, ovarian torsion, or both. Although asymmetric ovarian edema occurred more frequently in patients with torsion than without, in pregnant patients with stimulated ovaries referred for MRI (typically after non-diagnostic ultrasound), ovarian torsion could not be confidently diagnosed or excluded retrospectively with non-contrast MRI.

Elevated progesterone and its impact on birth weight after fresh embryo transfers.

PURPOSE: The purpose of the study was to examine the association between serum progesterone levels on the day of hCG administration and birth weight among singleton live births after fresh embryo transfer. METHODS: This study was conducted as a retrospective cohort database analysis on patients who underwent IVF treatment cycles from January 2004 to April 2012. The study was performed at a University affiliated private infertility practice. All cycles that had achieved a singleton live birth after fresh embryo transfer and for which progesterone was measured on the day of hCG administration were examined. Generalized linear models were used to calculate mean birth weight and z-scores. RESULTS: We analyzed 817 fresh IVF embryo transfers in which birth weight, gestational age, and progesterone (ng/mL) level on day of hCG administration were documented. While there was a decrease in birth weight as progesterone quartile [≤0.54; >0.54 to ≤0.81; >0.81 to ≤1.17; >1.17 ng/mL] increased, the difference in mean birth weights among the four quartiles was not statistically significant (p = 0.11) after adjusting for maternal age and peak estradiol levels. When dichotomizing based on a serum progesterone considered clinically elevated, cycles with progesterone >2.0 ng/mL had a significantly lower mean singleton birth weight (2860 g (95% CI 2642 g, 3079 g)) compared to cycles with progesterone ≤2.0 ng/mL (3167 g (95% CI 3122 g, 3211 g) p = 0.007)) after adjusting for maternal age and estradiol. CONCLUSION: We demonstrated that caution should be exercised when performing fresh embryo transfers with elevated progesterone levels and in particular with levels (>2.0 ng/mL) as this may lead to lower birth weight.

No change in live birthweight of IVF singleton deliveries over an 18-year period despite significant clinical and laboratory changes.

STUDY QUESTION: Has live birthweight changed over 18 years of autologous fresh and frozen IVF? SUMMARY ANSWER: Regardless of changes in clinical care and laboratory practice over 18 years, birthweight has remained stable. WHAT IS KNOWN ALREADY: Birthweight has historically been used as a marker of neonatal health. Frozen embryo transfers lead to heavier live birthweights compared with fresh embryo transfers. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study included 7295 singletons from autologous fresh (n = 6265) and frozen (n = 1030) IVF cycles from 1996 to 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients undergoing autologous IVF cycles between 1996 and 2013 resulting in a singleton live born with a birthweight recorded were included. One-way ANOVA and t-tests compared mean live birthweight in fresh and frozen cycles in 6-month increments over 18 years. Linear regression analysis was performed to investigate predictors of birthweight. MAIN RESULTS AND THE ROLE OF CHANCE: Mean birthweight after fresh (3283 ± 601 g) and frozen (3462 ± 621 g) cycles were significantly different (P < 0.001). ANOVA demonstrated no significant difference in mean weight from fresh or frozen cycles over 6-month intervals. No difference in weight was noted between Days 3 and 5 transfers or between ICSI and standard IVF. No difference was found across known changes when comparing media, laboratory location, cryopreservation method or gonadotrophins. LIMITATIONS, REASONS FOR CAUTION: Limitations include the small number of frozen low birthweight neonates. WIDER IMPLICATIONS OF THE FINDINGS: Our study suggests that changes in IVF practice, with the exception of fresh or frozen embryo transfer, have little impact on mean live birthweight. STUDY FUNDING/COMPETING INTERESTS: No funding was received for this study. The authors have no conflicting interests. TRIAL REGISTRATION NUMBER: Not applicable.

A randomized clinical trial to determine optimal infertility treatment in older couples: the Forty and Over Treatment Trial (FORT-T).

OBJECTIVE: To determine the optimal infertility therapy for women at the end of their reproductive potential. DESIGN: Randomized clinical trial. SETTING: Academic medical centers and private infertility center in a state with mandated insurance coverage. PATIENT(S): Couples with ≥ 6 months of unexplained infertility; female partner aged 38-42 years. INTERVENTION(S): Randomized to treatment with two cycles of clomiphene citrate (CC) and intrauterine insemination (IUI), follicle stimulating hormone (FSH)/IUI, or immediate IVF, followed by IVF if not pregnant. MAIN OUTCOME MEASURE(S): Proportion with a clinically recognized pregnancy, number of treatment cycles, and time to conception after two treatment cycles and at the end of treatment. RESULT(S): We randomized 154 couples to receive CC/IUI (N = 51), FSH/IUI (N = 52), or immediate IVF (N = 51); 140 (90.9%) couples initiated treatment. The cumulative clinical pregnancy rates per couple after the first two cycles of CC/IUI, FSH/IUI, or immediate IVF were 21.6%, 17.3%, and 49.0%, respectively. After all treatments, 110 (71.4%) of 154 couples had conceived a clinically recognized pregnancy, and 46.1% had delivered at least one live-born baby; 84.2% of all live-born infants resulting from treatment were achieved via IVF. There were 36% fewer treatment cycles in the IVF arm compared with either COH/IUI arm, and the couples conceived a pregnancy leading to a live birth after fewer treatment cycles. CONCLUSION(S): A randomized controlled trial in older women with unexplained infertility to compare treatment initiated with two cycles of controlled ovarian hyperstimulation/IUI versus immediate IVF demonstrated superior pregnancy rates with fewer treatment cycles in the immediate IVF group. CLINICAL TRIAL REGISTRATION NUMBER: NCT00246506.

Effect of steroid and antibiotic treatment during assisted hatching on IVF outcomes.

There are limited data on the use of steroids and antibiotics in assisted reproductive technology (ART). Our aim was to evaluate the impact of these treatments on the outcome of IVF cycles in which Assisted Hatching (AH) was performed. We studied a retrospective cohort in a large university-affiliated infertility centre. Data from 1126 AH cycles performed between 2007 and 2009 were reviewed. Cycles were categorized as "treatment" (n = 640) and "no treatment" (n = 486), depending on whether they received steroids and antibiotics. The primary outcome was live birth. Secondary outcomes included implantation, spontaneous abortion, biochemical, clinical and ectopic pregnancy. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). OR were adjusted (AOR) for age, BMI, baseline FSH, peak estradiol, cycle number, number of oocytes retrieved, number of embryos that underwent AH, number of high-implantation potential embryos, number of embryos transferred and physician in charge. The AOR (95% CI) of live birth was 1.91 (1.08-3.38), of clinical pregnancy, 1.75 (1.08-2.83) and of biochemical pregnancy, 0.24 (0.07-0.85). Our study suggests that treatment with steroids and antibiotics during AH cycles significantly increases the odds of live birth.

Race matters: a systematic review of racial/ethnic disparity in Society for Assisted Reproductive Technology reported outcomes.

OBJECTIVE: To systematically review the reporting of race/ethnicity in Society for Assisted Reproductive Technology (SART) Clinic Outcome Reporting System (CORS) publications. DESIGN: Systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology of literature published in PubMed on race/ethnicity that includes data from SART CORS. SETTING: Not applicable. PATIENT(S): Not applicable. INTERVENTION(S): In vitro fertilization cycles reported to SART. MAIN OUTCOME MEASURE(S): Any outcomes reported in SART CORS. RESULT(S): Seven publications were identified that assessed racial/ethnic disparities in IVF outcomes using SART data. All reported a racial/ethnic disparity. However, more than 35% of cycles were excluded from analysis because of missing race/ethnicity data. CONCLUSION(S): Review of current publications of SART data suggests significant racial/ethnic disparities in IVF outcomes. However, the potential for selection bias limits confidence in these findings, given that fewer than 65% of SART reported cycles include race/ethnicity. Our understanding of how race/ethnicity influences ART outcome could be greatly improved if information on race/ethnicity was available for all reported cycles.

Contraceptive counseling for women who undergo bariatric surgery.

BACKGROUND: Women are counseled to avoid becoming pregnant for 12-24 months after bariatric surgery. The aim of this study was to assess contraceptive counseling and use in women who undergo bariatric surgery. METHODS: A self-administered survey was completed by women aged 18-45 years at a postoperative clinic visit >2 months after bariatric surgery at an urban teaching hospital. RESULTS: Of the 69 respondents, 94.2% knew to avoid pregnancy for at least 12 months after surgery. However, 16.3% did not use any contraception 2-12 months after surgery. The most common contraceptive methods used were condoms (30.6%) and oral contraceptives (16.3%). Longer-acting reversible contraceptives were used less frequently; for example, only 4% of women used intrauterine devices. Only 21.2% of respondents were referred to an obstetrician/gynecologist for contraceptive counseling. CONCLUSIONS: Many women who undergo bariatric surgery are not using very effective contraceptive methods or any contraception. There is a clear opportunity to improve counseling and increase use of more effective contraception in this population.

Influence of embryo sex on development to the blastocyst stage and euploidy.

OBJECTIVE: To compare the prevalence of blastocyst development and euploidy in XX versus XY embryos. DESIGN: Retrospective cohort study. SETTING: Boston IVF, a large university-affiliated reproductive medicine practice. PATIENT(S): All patients who underwent their first preimplantation genetic screening cycle between January 1, 2006, and December 31, 2007. INTERVENTION(S): In vitro fertilization and preimplantation genetic screening. MAIN OUTCOME MEASURE(S): Proportion of embryos that developed to the blastocyst stage by day 5 and prevalence of euploidy for chromosomes 8, 13, 14, 15, 16, 17, 18, 20, 21, and 22 in XX versus XY embryos. RESULT(S): Seven hundred fifty-eight embryos from 138 cycles in 138 patients were analyzed. Three hundred sixty-six (48%) were XX, and 392 (52%) were XY. XX and XY embryos were equally likely to develop to the blastocyst stage by day 5 and were equally likely to be euploid for the analyzed chromosomes. CONCLUSION(S): Our data suggest that extending embryo culture to day 5 does not lead to sex selection and that euploidy and aneuploidy are not sex dependent.

Follicular fluid-specific distribution of vascular endothelial growth factor isoforms and sFlt-1 in patients undergoing IVF and their correlation with treatment outcomes.

OBJECTIVE: To investigate the distribution of vascular endothelial growth factor (VEGF) isoforms and soluble form of VEGF receptor 1 (sFlt-1) in the follicular fluid (FF) of in vitro fertilization (IVF) patients in relationship to age, body mass index (BMI), diagnosis of polycystic ovary syndrome (PCOS), and their correlation with IVF outcomes. DESIGN: Prospective study. MAIN OUTCOME MEASURES: VEGF( 121) and VEGF(165) isoforms were detected using Western blotting and pixel density analysis. The concentration of sFlt-1 was determined by enzyme-linked immunosorbent assay (ELISA). In vitro fertilization outcomes measured included number of oocytes retrieved, fertilization rate, and clinical pregnancy. Statistical analysis used the Kruskal-Wallis and Mann-Whitney U test where appropriate. RESULTS: There was a statistically significant association between higher VEGF(165) levels and the diagnosis of PCOS, BMI ≥ 30, and age ≥40 years. In vitro fertilization cycles resulting in pregnancy were linked to statistically lower VEGF(165) levels in the FF. No statistically significant trend was identified in levels of VEGF(121) or sFlt-1 relative to patient characteristics or IVF outcomes. CONCLUSION: Our results suggest that elevated VEGF(165) levels are associated with less favorable patient characteristics and clinical IVF outcomes.

A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and standard treatment (FASTT) trial.

OBJECTIVE: To determine the value of gonadotropin/intrauterine insemination (FSH/IUI) therapy for infertile women aged 21-39 years. DESIGN: Randomized controlled trial. SETTING: Academic medical center associated with a private infertility center. PATIENT(S): Couples with unexplained infertility. INTERVENTION(S): Couples were randomized to receive either conventional treatment (n=247) with three cycles of clomiphene citrate (CC)/IUI, three cycles of FSH/IUI, and up to six cycles of IVF or an accelerated treatment (n=256) that omitted the three cycles of FSH/IUI. MAIN OUTCOME MEASURE(S): The time it took to establish a pregnancy that led to a live birth and cost-effectiveness, defined as the ratio of the sum of all health insurance charges between randomization and delivery divided by the number of couples delivering at least one live-born baby. RESULT(S): An increased rate of pregnancy was observed in the accelerated arm (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.00-1.56) compared with the conventional arm. Median time to pregnancy was 8 and 11 months in the accelerated and conventional arms, respectively. Per cycle pregnancy rates for CC/IUI, FSH/IUI, and IVF were 7.6%, 9.8%, and 30.7%, respectively. Average charges per delivery were $9,800 lower (95% CI, $25,100 lower to $3,900 higher) in the accelerated arm compared to conventional treatment. The observed incremental difference was a savings of $2,624 per couple for accelerated treatment and 0.06 more deliveries. CONCLUSION(S): A randomized clinical trial demonstrated that FSH/IUI treatment was of no added value.

Influence of patient age on the association between euploidy and day-3 embryo morphology.

A retrospective cohort study conducted in 138 patients undergoing their first preimplantation genetic screening (PGS) cycle between January 1, 2006, and December 31, 2007, demonstrated that embryos with good day-3 morphology were more likely to be euploid for X/Y, 8, 15, and 18 than those with poor morphology. The strength of association between euploidy and day-3 morphology was not influenced by maternal age.