The Association of Female and Male Preconception Dyslipidemia with Live Birth in Couples Seeking Fertility Treatment.

CONTEXT: Dyslipidemia is common, and resultant endothelial dysfunction may impact reproductive outcomes. No prospective study has examined the effect of preconception lipid parameters in both female and male partners or their interaction on live birth. OBJECTIVE: To determine whether live birth is associated with preconception lipids in both partners by planned fertility treatment. DESIGN: Secondary analysis of the Folic Acid and Zinc Supplementation Trial, conducted between June 2013-December 2017. Couples were followed for nine months after randomization and until delivery. SETTING: Multicenter study. PARTICIPANTS: Couples seeking fertility treatment (n = 2370; females 18-45 years, males ≥18 years). EXPOSURES: Female, male, and couple abnormal versus normal preconception lipid concentrations (total cholesterol [TC], low-density lipoprotein [LDL], high-density lipoprotein [HDL], triglycerides [TG]). MAIN OUTCOME MEASURES: Live birth. RESULTS: Among 2370 couples, most males (84%) and females (76%) had at least one abnormal lipid parameter. Males planning in vitro fertilization (IVF, n = 373) with elevated LDL had lower probability of live birth than those with normal levels (47.4% vs. 59.7%, aRR 0.79, 95% CI 0.65-0.98). In couples planning IVF where both partners had elevated TC or LDL, live birth was lower than those with normal levels (TC: 32.4% vs. 58.0%, aRR 0.53, 95% CI 0.36-0.79; and LDL: 41.9% vs. 63.8%, aRR 0.69, 95% CI 0.55-0.85). Lipid parameters were not associated with live birth for couples planning non-IVF treatments. CONCLUSIONS: Couples planning IVF where both partners had elevated TC or LDL and males planning IVF with elevated LDL had decreased probability of live birth. These findings may support lipid screening in patients seeking fertility treatment for prognostic information for reproductive outcomes.

Cumulative live birth rate in women aged ≤37 years after in vitro fertilization with or without preimplantation genetic testing for aneuploidy: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System retrospective analysis.

Objective: To investigate cumulative live birth rates (CLBRs) in cycles with and without preimplantation genetic testing for aneuploidy (PGT-A) among patients aged <35 and 35-37 years. Design: Retrospective cohort study. Setting: Society for Assisted Reproductive Technology reporting clinics. Patients: A total of 31,900 patients aged ≤ 37 years with initial oocyte retrievals between January 2014 and December 2015 followed through December 2016. Interventions: None. Main outcome measures: The primary outcome was CLBR among patients aged <35 and 35-37 years. The secondary outcomes included multifetal births, miscarriage, preterm birth, perinatal mortality, and the time to pregnancy resulting in a live birth. Adjusted odds ratios (aORs) adjusting for age, body mass index, total 2 pronuclei embryos, embryos transferred, and follow-up timeframe. Results: Among patients aged <35 years, PGT-A was associated with reduced CLBRs (70.6% vs. 71.1%; aOR, 0.82; 95% CI [confidence interval], 0.72-0.93). No association was found between PGT-A and CLBRs among patients aged 35-37 years (66.6% vs. 62.5%; aOR, 0.92; 95% CI, 0.83-1.01). Overall, there was no significant difference in the miscarriage rate (aOR, 0.97; 95% CI, 0.82-1.14). Multifetal birth rates were lower with PGT-A (9.5% vs. 23.1%); however, PGT-A was not an independent predictor of multifetal birth (aOR, 1.11; 95% CI, 0.91-1.36). The average time to pregnancy resulting in a live birth was 2.37 months (SD 3.20) for untested transfers vs. 4.58 months (SD 3.53) for PGT-A transfers. Conclusions: In women aged <35, the CLBR was lower with PGT-A than with the transfer of untested embryos. In women aged 35-37 years, PGT-A did not improve CLBRs.

Low oocyte maturity ratio is associated with a reduced in vitro fertilization and intracytoplasmic sperm injection live birth rate.

OBJECTIVE: To determine whether a low oocyte maturity ratio in a cohort of oocytes from an in vitro fertilization cycle predicts outcomes and to examine clinical factors associated with oocyte maturity. DESIGN: A retrospective cohort study. SETTING: An academic medical center. INTERVENTION(S): Determination of oocyte maturity immediately after the retrieval and 6 hours later if intracytoplasmic sperm injection was performed. MAIN OUTCOME MEASURE(S): The primary outcome was live birth rate after the first embryo transfer. Secondary outcomes included clinical pregnancy, miscarriage, and fertilization rates. RESULT(S): After adjusting for age, preimplantation genetic testing, and number of embryos transferred, we found that a low oocyte maturity ratio was associated with a decreased live birth rate (adjusted odds ratio [AOR], 0.41; 95% confidence interval [CI], 0.22-0.77) and clinical pregnancy rate (AOR, 0.32; 95% CI, 0.17-0.61). We did not find a relationship between oocyte maturity and miscarriage rate (AOR, 0.25; 95% CI, 0.03-1.91) or fertilization rate (Welch test). The number of 2 pronuclei embryos per retrieved oocyte was found to be associated with the maturity ratio at retrieval. Patients with anovulation had slightly reduced oocyte maturity compared with other diagnostic groups. CONCLUSION(S): Low oocyte maturity ratio is an important factor related to poor in vitro fertilization outcomes, including decreased pregnancy and live birth rates.

Intracytoplasmic sperm injection vs. conventional in vitro fertilization in patients with non-male factor infertility.

OBJECTIVE: To compare the cumulative live birth rates (CLBRs) and cost effectiveness of intracytoplasmic sperm injection (ICSI) and conventional in vitro fertilization (cIVF) for non-male factor infertility. DESIGN: A retrospective cohort study. SETTING: Society for Assisted Reproductive Technology clinics. PATIENT(S): A total of 46,967 patients with non-male factor infertility with the first autologous oocyte retrieval cycle between January 2014 and December 2015. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcomes were CLBR, defined as up to 1 live birth from an autologous retrieval cycle between 2014 and 2015, and linked fresh and frozen embryo transfers through 2016. The secondary outcomes included miscarriage rate, 2 pronuclei per oocyte retrieved, and the total number of transferred and frozen embryos. Analyses were performed on subsamples with and without preimplantation genetic testing for aneuploidy (PGT-A). A cost analysis was performed to determine the costs accrued by ICSI. RESULT(S): Among cycles without PGT-A in patients with non-male factor infertility, the CLBR was 60.9% for ICSI cycles vs. 64.3% for cIVF cycles, a difference that was not significantly different after adjustment for covariates (adjusted risk ratio, 0.99; 95% confidence interval, 0.99-1.00). With PGT-A, no difference in CLBR was found between ICSI and cIVF cases after adjustment (64.7% vs. 69.0%, respectively; adjusted risk ratio, 0.97; 95% confidence interval, 0.93-1.01). The patients were charged an estimated additional amount of $37,476,000 for ICSI without genetic testing and an additional amount of $7,213,500 for ICSI with PGT-A over 2 years by Society for Assisted Reproductive Technology clinics. CONCLUSION(S): In patients with non-male factor infertility, ICSI did not improve CLBR. Given the additional cost and the lack of CLBR benefit, our data show that the routine use of ICSI in patients with non-male factor infertility is not warranted.

Fresh embryo transfer after in vitro insemination of fresh vs. cryopreserved anonymous donor oocytes: which has a better live birth rate? A Society for Assisted Reproductive Technology Clinic Outcome Reporting System analysis.

OBJECTIVE: To determine if transfer of fresh embryos derived from fresh or cryopreserved donor oocytes yields a higher live birth rate. DESIGN: Historical cohort study. SETTING: Society for Assisted Reproductive Technology Clinic Outcome Reporting System database. PATIENT(S): A total of 24,663 fresh embryo transfer cycles of donor oocytes. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was live births per number of embryos transferred on day 5. The secondary outcomes included number of infants per embryo transfer, surplus embryos cryopreserved, and characterization of US oocyte recipients. RESULT(S): A total of 16,073 embryo transfers were from fresh oocytes and 8,590 were from cryopreserved oocytes. Recipient age, body mass index (BMI), gravidity, and parity were similar between the groups. Most recipients were of White non-Hispanic race (66.9%), followed by Asian (13.7%), Black non-Hispanic (9.3%), and Hispanic (7.2%). Fresh oocyte cycles were more likely to use elective single embryo transfer (42.5% vs. 37.8%) or double embryo transfer (53.2% vs. 50.4%) and resulted in more surplus embryos for cryopreservation (4.6 vs. 1.2). The live birth rate from fresh oocytes was 57.5% vs. 49.7% from cryopreserved oocytes. Negative predictors of live birth included the use of cryopreserved oocytes (odds ratio [OR] 0.731, 95% confidence interval [CI] 0.665-0.804), Black non-Hispanic race (OR 0.603, 95% CI 0.517-0.703), Asian race (OR 0.756, 95% CI 0.660-0.867), and increasing recipient BMI (OR 0.982, 95% CI 0.977-0.994) after controlling for recipient age, number of embryos transferred on day 5, and unexplained infertility diagnosis. The proportion of multifetal deliveries was greater in cycles utilizing fresh (26.4%) vs. cryopreserved (20.6%) oocytes. CONCLUSION(S): The live birth rate is higher with use of fresh oocytes vs. cryopreserved oocytes in fresh embryo transfer cycles. Negative live birth predictors include recipient Black non-Hispanic or Asian race and increasing BMI.

Predicting personalized cumulative live birth following in vitro fertilization.

OBJECTIVE: To develop in vitro fertilization (IVF) prediction models to estimate the individualized chance of cumulative live birth at two time points: pretreatment (i.e., before starting the first complete cycle of IVF) and posttreatment (i.e., before starting the second complete cycle of IVF in those couples whose first complete cycle was unsuccessful). DESIGN: Population-based cohort study. SETTING: National data from the Society for Assisted Reproductive Technology (SART) Clinic Outcome Reporting System. PATIENT(S): Based on 88,614 women who commenced IVF treatment using their own eggs and partner's sperm in SART member clinics. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): The pretreatment model estimated the cumulative chance of a live birth over a maximum of three complete cycles of IVF, whereas the posttreatment model did so over the second and third complete cycles. One complete cycle included all fresh and frozen embryo transfers resulting from one episode of ovarian stimulation. We considered the first live birth episode, including singletons and multiple births. RESULT(S): Pretreatment predictors included woman's age (35 years vs. 25 years, adjusted odds ratio 0.69, 95% confidence interval 0.66-0.73) and body mass index (35 kg/m2 vs. 25 kg/m2, adjusted odds ratio 0.75, 95% confidence interval 0.72-0.78). The posttreatment model additionally included the number of eggs from the first complete cycle (15 vs. 9 eggs, adjusted odds ratio 1.10, 95% confidence interval 1.03-1.18). According to the pretreatment model, a nulliparous woman aged 34 years with a body mass index of 23.3 kg/m2, male partner infertility, and an antimüllerian hormone level of 3 ng/mL has a 61.7% chance of having a live birth over her first complete cycle of IVF (and a cumulative chance over three complete cycles of 88.8%). If a live birth is not achieved, according to the posttreatment model, her chance of having a live birth over the second complete cycle 1 year later (age 35 years, number of eggs 7) is 42.9%. The C-statistic for all models was between 0.71 and 0.73. CONCLUSION(S): The focus of previous IVF prediction models based on US data has been cumulative live birth excluding cycles involving frozen embryos. These novel prediction models provide clinically relevant estimates that could help clinicians and couples plan IVF treatment at different points in time.

Common practices among consistently high-performing in vitro fertilization programs in the United States: 10-year update.

OBJECTIVE: To evaluate similarities and differences in clinical and laboratory practices among high-performing fertility clinics. DESIGN: Cross-sectional questionnaire study of selected programs. SETTING: Academic and private fertility practices performing in vitro fertilization (IVF). PATIENT(S): Not applicable. INTERVENTION(S): A comprehensive survey was conducted of 13 IVF programs performing at least 100 cycles a year and having high cumulative singleton delivery rates for 2 years. MAIN OUTCOME MEASURE(S): Clinical and laboratory IVF practices. RESULT(S): Although many areas of clinical practice varied among top programs, some commonalities were observed. All programs used a combination of follicle-stimulating hormone and luteinizing hormone for IVF stimulation, intramuscular progesterone in frozen embryo transfer cycles, ultrasound-guided embryo transfers, and a required semen analysis before starting the IVF cycle. Common laboratory practices included vitrification of embryos at the blastocyst stage, air quality control with positive air pressure and high-efficiency particulate air filtration, use of incubator gas filters, working on heated microscope stages, and incubating embryos in a low-oxygen environment, most often in benchtop incubators. CONCLUSION(S): Some areas of consistency in clinical and laboratory practices were noted among high-performing IVF programs that are likely contributing to their success. High-performing programs focused on singleton deliveries. As the field of IVF is rapidly evolving, it is imperative that we share best practices in an effort to improve outcomes from all clinics for the good of our patients.

Elective transfer of one embryo is associated with a higher cumulative live birth rate and improved perinatal outcomes compared to the transfer of two embryos with in vitro fertilization.

OBJECTIVE: To compare the effects of initial elective single embryo transfer (ieSET) and initial double embryo transfer (iDET) strategies on the cumulative live birth rate (CLBR) and perinatal outcomes after IVF. DESIGN: Retrospective cohort study. SETTING: Society for Assisted Reproductive Technology (SART) reporting clinics. PATIENTS: 49,333 patients with initial oocyte retrievals between January 2014 and December 2015. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The primary outcome was CLBR, defined as up to 1 live birth resulting from a retrieval cycle and linked transfer cycles. Secondary outcomes included cycles to pregnancy, multifetal delivery rate, infant birthweight, and perinatal mortality rate. RESULTS: Compared to iDET, ieSET was associated with increased CLBR (74% vs. 57%; adjusted odds ratio [AOR], 1.32; 95% CI, 1.26-1.38). When stratified by age, the same trend was seen in all age categories, with statistical significance for those <38 years of age. ieSET was associated with reduced multifetal delivery (8% vs. 34%; AOR, 0.13; 95% CI, 0.12-0.14), increased birthweight (mean difference, 406 grams; 95% CI, 387-425), reduced preterm births (1.2% vs. 2.8%), and reduced perinatal mortality (0.5% vs. 1.2%). Compared with iDET, ieSET was associated with slightly more embryo transfer cycles (1.7 vs. 1.4 cycles; AOR, 1.19; 95% CI, 1.16-1.21) to achieve a pregnancy resulting in live birth. CONCLUSIONS: The association of ieSET with a higher CLBR and markedly improved perinatal outcomes outweigh the relatively minor increase in time to pregnancy, reinforcing the guidance for eSET in initial transfer cycles, particularly in younger patients with a good prognosis.

The effect of weight and body mass index on serum progesterone values and live birth rate in cryopreserved in vitro fertilization cycles.

OBJECTIVE: To determine if weight or body mass index (BMI) affects the serum progesterone level at the time of the pregnancy test in cryopreserved blastocyst transfer cycles and to determine if those serum progesterone levels affect live births. DESIGN: Retrospective cohort study. SETTING: US academic medical center. PATIENTS: Six hundred thirty-three patients undergoing their first cryopreserved embryo transfer cycle. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The primary outcome was the serum progesterone level on the day of the pregnancy test by patient weight and BMI. Our secondary analysis assessed the serum progesterone effect on live birth rate (LBR) in a clinic where progesterone supplementation was increased if the progesterone level was <15 ng/mL on the day of the pregnancy test. RESULTSS: There was a strong negative correlation between serum progesterone level and both BMI and weight, with BMI accounting for 27% and weight accounting for 29% of the variance in progesterone level. Serum progesterone level on the day of the pregnancy test was <15 ng/mL in 3% of women weighing <68 kg compared with 29% of women weighing ≥90.7 kg. Among women weighing ≥90.7 kg, live birth occurred in 47% whose serum progesterone level was <15 ng/mL on the day of the pregnancy test compared with 49% in those with serum progesterone level of 15-19 ng/mL and 44% in those with serum progesterone level of ≥20 ng/mL. CONCLUSIONS: Body weight was a significant factor in serum progesterone level at the time of the pregnancy test, with nearly 30% of patients weighing ≥90.7 kg having serum progesterone level of <15 ng/mL, a value associated with lower LBRs in prior studies. However, we found no effect of low progesterone levels on LBR after cryopreserved embryo transfer cycles in a clinic where progesterone dosing was increased if serum progesterone levels were <15 ng/mL.

Effect of body mass index on intrauterine insemination cycle success.

OBJECTIVE: To determine whether body mass index (BMI) affects intrauterine insemination treatment success. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): A total of 3,217 intrauterine insemination treatment cycles in 1,306 patients. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Primary outcome was live birth rate stratified by BMI. Secondary outcomes included rates of clinical pregnancy (defined as an intrauterine pregnancy with a heartbeat present on ultrasound), multiple gestation, biochemical pregnancy, missed abortion, ectopic, and spontaneous abortion. RESULT(S): Women with BMI 25 to 29.99 kg/m2 or ≥30 kg/m2 were equally likely to have a live birth as women of normal BMI. Women with BMI ≥30 kg/m2 did have a higher likelihood of biochemical pregnancy than women with normal BMI. CONCLUSION(S): A BMI between 25 and 29.99 kg/m2 or ≥30 kg/m2 does not appear to have a negative effect on live birth after intrauterine insemination. Obesity may be associated with a higher risk of biochemical pregnancy after intrauterine insemination.

Current evidence supporting a goal of singletons: a review of maternal and perinatal outcomes associated with twin versus singleton pregnancies after in vitro fertilization and intracytoplasmic sperm injection.

With increasing use of in vitro fertilization and intracytoplasmic sperm injection (IVF-ICSI) almost 2% of all babies born in the United States each year are now conceived with these technologies, making outcomes of IVF-ICSI extremely important not only to patients and families but to public health. Twin pregnancy rates after IVF-ICSI in the United States have declined since their peak in 2013 but remain at approximately 1 in 10 to 1 in 20 pregnancies. A review of the current international literature on twin versus singleton pregnancy outcomes after IVF-ICSI treatment confirms statistically significantly higher risks to maternal and perinatal health and statistically significantly higher health care costs. The field of infertility care should continue to work to develop practices that lower twin pregnancy rates to an absolute minimum to maximize the safety of these medical treatments.

Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment: A Randomized Clinical Trial.

Importance: Dietary supplements marketed for male fertility commonly contain folic acid and zinc based on limited prior evidence for improving semen quality. However, no large-scale trial has examined the efficacy of this therapy for improving semen quality or live birth. Objective: To determine the effect of daily folic acid and zinc supplementation on semen quality and live birth. Design, Setting, and Participants: The Folic Acid and Zinc Supplementation Trial was a multicenter randomized clinical trial. Couples (n = 2370; men aged ≥18 years and women aged 18-45 years) planning infertility treatment were enrolled at 4 US reproductive endocrinology and infertility care study centers between June 2013 and December 2017. The last 6-month study visit for semen collection occurred during August 2018, with chart abstraction of live birth and pregnancy information completed during April 2019. Interventions: Men were block randomized by study center and planned infertility treatment (in vitro fertilization, other treatment at a study site, and other treatment at an outside clinic) to receive either 5 mg of folic acid and 30 mg of elemental zinc (n = 1185) or placebo (n = 1185) daily for 6 months. Main Outcomes and Measures: The co-primary outcomes were live birth (resulting from pregnancies occurring within 9 months of randomization) and semen quality parameters (sperm concentration, motility, morphology, volume, DNA fragmentation, and total motile sperm count) at 6 months after randomization. Results: Among 2370 men who were randomized (mean age, 33 years), 1773 (75%) attended the final 6-month study visit. Live birth outcomes were available for all couples, and 1629 men (69%) had semen available for analysis at 6 months after randomization. Live birth was not significantly different between treatment groups (404 [34%] in the folic acid and zinc group and 416 [35%] in the placebo group; risk difference, -0.9% [95% CI, -4.7% to 2.8%]). Most of the semen quality parameters (sperm concentration, motility, morphology, volume, and total motile sperm count) were not significantly different between treatment groups at 6 months after randomization. A statistically significant increase in DNA fragmentation was observed with folic acid and zinc supplementation (mean of 29.7% for percentage of DNA fragmentation in the folic acid and zinc group and 27.2% in the placebo group; mean difference, 2.4% [95% CI, 0.5% to 4.4%]). Gastrointestinal symptoms were more common with folic acid and zinc supplementation compared with placebo (abdominal discomfort or pain: 66 [6%] vs 40 [3%], respectively; nausea: 50 [4%] vs 24 [2%]; and vomiting: 32 [3%] vs 17 [1%]). Conclusions and Relevance: Among a general population of couples seeking infertility treatment, the use of folic acid and zinc supplementation by male partners, compared with placebo, did not significantly improve semen quality or couples' live birth rates. These findings do not support the use of folic acid and zinc supplementation by male partners in the treatment of infertility. Trial Registration: ClinicalTrials.gov Identifier: NCT01857310.

A Randomized Trial to Evaluate the Effects of Folic Acid and Zinc Supplementation on Male Fertility and Livebirth: Design and Baseline Characteristics.

The Folic Acid and Zinc Supplementation Trial (FAZST) was a multicenter, double-blind, block-randomized, placebo-controlled trial to determine whether folic acid and zinc supplementation in men improves semen quality and increases livebirth rate among couples seeking infertility treatment (2013-2017). Eligible men were aged 18 years or older with female partners aged 18-45 years, seeking infertility treatment. Men were randomized (1:1) to 5 mg folic acid and 30 mg elemental zinc daily or matching placebo for 6 months. Randomization was stratified by site and intended infertility treatment (in vitro fertilization (IVF), non-IVF/study site, and non-IVF/outside clinic). Follow-up of men continued for 6 months, and female partners were passively followed for a minimum of 9 months. Women who conceived were followed throughout pregnancy. Overall, 2,370 men were randomized during 2013-2017 (1,185 folic acid and zinc, 1,185 placebo); they had a mean age of 33 years and body mass index (weight (kg)/height (m)2) of 29.8. Most participants were white (82%), well educated (83% with some college), and employed (72%). Participant characteristics were balanced across intervention arms. Study visits were completed by 89%, 77%, and 75% of men at months 2, 4, and 6, respectively. Here we describe the study design, recruitment, data collection, lessons learned, and baseline participant characteristics.

A randomized controlled trial of combination letrozole and clomiphene citrate or letrozole alone for ovulation induction in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate whether a combination of letrozole and clomiphene citrate (CC) results in higher ovulation rates than letrozole alone in infertile women with polycystic ovary syndrome (PCOS). DESIGN: Open-label randomized controlled trial. SETTING: Academic medical center using two clinic sites. PATIENT(S): Women 18-40 years of age with a diagnosis of infertility and PCOS as defined by the Rotterdam criteria and no other known cause of infertility. INTERVENTIONS(S): Participants were randomized in a 1:1 ratio, stratified by age and body mass index, to either 2.5 mg letrozole alone or the combination of 2.5 mg letrozole and 50 mg CC daily on cycle days 3-7 for one treatment cycle. MAIN OUTCOME MEASURE(S): Ovulation defined as mid-luteal serum progesterone concentration ≥3 ng/mL. RESULT(S): Seventy patients were randomized: 35 to letrozole alone and 35 to letrozole and CC. Results were analyzed according to the intention-to-treat principle. Women who received the combination of letrozole and CC had a statistically higher ovulation rate compared with those who received letrozole alone (27 of 35 women [77%] vs. 15 of 35 women [43%]). There were no serious adverse events or multiple-gestation pregnancies in either group. The side-effects profile was similar in the two treatment groups. CONCLUSION(S): The combination of letrozole and CC was associated with a higher ovulation rate compared with letrozole alone in women with infertility and PCOS. Further studies are needed to evaluate the effect on live birth rate. CLINICAL TRIAL REGISTRATION NUMBER: NCT02802865.

Risk of prematurity and infant morbidity and mortality by maternal fertility status and plurality.

PURPOSE: To evaluate the risk of prematurity and infant mortality by maternal fertility status, and for in vitro fertilization (IVF) pregnancies, by oocyte source and embryo state combinations. METHODS: Women in 14 States who had IVF-conceived live births during 2004-13 were linked to their infant's birth and death certificates; a 10:1 sample of non-IVF births was selected for comparison; those with an indication of infertility treatment on the birth certificate were categorized as subfertile, all others were categorized as fertile. Risks were modeled separately for the fertile/subfertile/IVF (autologous-fresh only) group and for the IVF group by oocyte source-embryo state combinations, using logistic regression, and reported as adjusted odds ratios (AORs) and 95% confidence intervals (CI). RESULTS: The study population included 2,474,195 pregnancies. Placental complications (placenta previa, abruptio placenta, and other excessive bleeding) and prematurity were both increased with pregestational and gestational diabetes and hypertension, among subfertile and IVF groups, and in IVF pregnancies using donor oocytes. Both subfertile and IVF pregnancies were at risk for prematurity and NICU admission; IVF infants were also at risk for small-for-gestation birthweight, and subfertile infants had greater risks for neonatal and infant death. Within the IVF group, pregnancies with donor oocytes and/or thawed embryos were at greater risk of large-for-gestation birthweight, and pregnancies with thawed embryos were at greater risk of neonatal and infant death. CONCLUSIONS: Prematurity was associated with placental complications, diabetes and hypertension, subfertility and IVF groups, and in IVF pregnancies, donor oocytes and/or thawed embryos.

Effect of body weight on early hormone levels in singleton pregnancies resulting in delivery after in vitro fertilization.

OBJECTIVE: To evaluate which clinical characteristics influence early maternal ß-human chorionic gonadotropin (hCG) and progesterone levels in in vitro fertilization (IVF) pregnancies. DESIGN: Retrospective cohort analysis. SETTING: Academic medical center. PATIENT(S): Women with a live birth after single-blastocyst embryo transfer in either a fresh or frozen cycle between 2004 and 2017, comprising 1,282 pregnancies in 1,057 patients. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The initial human chorionic gonadotropin concentration (ß-hCG1) measured a mean of 10 days (range: 9-12 days) after embryo transfer, the rate of increase in ß-hCG concentrations, and progesterone concentration, with all analyses controlled for number of days between the embryo transfer and the ß-hCG1 measurement. RESULT(S): The clinical factor that positively influenced the ß-hCG1 level in the fresh cycle was the stimulation type (antagonist cycle higher than long agonist cycle). The clinical factors that negatively influenced both fresh and frozen cycle ß-hCG1 were lower embryo quality and increasing body weight. Increasing weight negatively impacted progesterone levels in both fresh and frozen cycles. A 100 lb (45.4 kg) difference in weight was associated with a 34.8% reduction in ß-hCG1 for both fresh and frozen cycle pregnancies. The rate of increase in ß-hCG was unaffected by body weight. A 100 lb (45.4 kg) difference in weight was associated with a 53.3% and a 32.8% reduction in progesterone in fresh and frozen cycles, respectively. CONCLUSION(S): Increasing body weight is associated with significantly lower ß-hCG and progesterone concentrations in early pregnancy after blastocyst single-embryo transfer in both fresh and frozen cycles. Clinicians should consider this when evaluating these hormone levels for prognostic and diagnostic purposes.