Distinct cytokine profiles in late pregnancy in Ugandan people with HIV.

During pregnancy, multiple immune regulatory mechanisms establish an immune-tolerant environment for the allogeneic fetus, including cellular signals called cytokines that modify immune responses. However, the impact of maternal HIV infection on these responses is incompletely characterized. We analyzed paired maternal and umbilical cord plasma collected during labor from 147 people with HIV taking antiretroviral therapy and 142 HIV-uninfected comparators. Though cytokine concentrations were overall similar between groups, using Partial Least Squares Discriminant Analysis we identified distinct cytokine profiles in each group, driven by higher IL-5 and lower IL-8 and MIP-1α levels in pregnant people with HIV and higher RANTES and E-selectin in HIV-unexposed umbilical cord plasma (P-value < 0.01). Furthermore, maternal RANTES, SDF-α, gro α -KC, IL-6, and IP-10 levels differed significantly by HIV serostatus (P < 0.01). Although global maternal and umbilical cord cytokine profiles differed significantly (P < 0.01), umbilical cord plasma profiles were similar by maternal HIV serostatus. We demonstrate that HIV infection is associated with a distinct maternal plasma cytokine profile which is not transferred across the placenta, indicating a placental role in coordinating local inflammatory response. Furthermore, maternal cytokine profiles in people with HIV suggest an incomplete shift from Th2 to Th1 immune phenotype at the end of pregnancy.

Development of a Model to Estimate the Optimal Number of Oocytes to Attempt to Fertilize During Assisted Reproductive Technology Treatment.

Importance: Surplus cryopreserved embryos pose a challenge for in vitro fertilization patients and clinics; with Roe v. Wade overturned, some states may deem the discarding of surplus embryos illegal, radically changing in vitro fertilization practice. An evidence-based tool would help limit surplus embryo creation. Objective: To develop a prediction tool for determining how many oocytes should be exposed to sperm to create embryos to conserve the chance of live birth while minimizing surplus embryos. Design, Setting, and Participants: This diagnostic study used data from member clinics of the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System between 2014 to 2019. A total of 410 719 oocyte retrievals and 460 577 embryo transfer cycles from 311 237 patients aged 18 to 45 years old who initiated their first oocyte stimulation cycle between January 1, 2014, and December 31, 2019, were included. Data were analyzed from February to June 2022. Exposures: Female patient age, anti-mullerian hormone level, diminished ovarian reserve diagnosis, number of oocytes retrieved, and the state where the clinic is located were included in the final models. Main Outcomes and Measures: The algorithm was based on 3 models with outcomes: (1) day of transfer; (2) proportion of retrieved oocytes that become usable blastocysts; and (3) number of blastocysts needed for transfer for 1 live birth to occur. Results: The median (IQR) age at stimulation cycle start was 35 (29-32) years and the median (IQR) number of oocytes retrieved was 10 (6-17). The likelihood of recommending that all oocytes be exposed to sperm increased with age; less than 20.0% of retrievals among patients younger than 32 years and more than 99.0% of retrievals among patients older than 42 years received recommendations that all oocytes be exposed to sperm. Among cycles recommended to expose fewer than all oocytes, the median (IQR) numbers recommended for 1 live birth were 7 oocytes (7-8) for patients aged less than 32 years, 8 (7-8) for patients aged 32 to 34 years, and 9 (9-11) for patients aged 35 to 37 years. Conclusions and Relevance: In this diagnostic study of in vitro fertilization cycles, a prediction tool was developed to aid clinicians in determining the optimal number of oocytes to expose to sperm, reducing the number of unused embryos created and immediately addressing current patient and clinician concerns.

State insurance mandates for in vitro fertilization are not associated with improving racial and ethnic disparities in utilization and treatment outcomes.

BACKGROUND: Racial and ethnic disparities in utilization and clinical outcomes following fertility care with in vitro fertilization in the United States are well-documented. Given the cost of fertility care, lack of insurance is a barrier to access across all races and ethnicities. OBJECTIVE: This study aimed to determine how state insurance mandates are associated with racial and ethnic disparities in in vitro fertilization utilization and clinical outcomes. STUDY DESIGN: This was a cohort study using data from the Society for Assisted Reproductive Technology Clinical Outcome Reporting System from 2014 to 2019 for autologous in vitro fertilization cycles. The primary outcomes were utilization-defined as the number of in vitro fertilization cycles per 10,000 reproductive-aged women-and cumulative live birth-defined as the delivery of at least 1 liveborn neonate resulting from a single stimulation cycle and its corresponding fresh or thawed transfers. RESULTS: Most (72.9%) of the 1,096,539 cycles from 487,191 women occurred in states without an insurance mandate. Although utilization was higher across all racial and ethnic groups in mandated states, the increase in utilization was greatest for non-Hispanic Asian and non-Hispanic White women. For instance, in the most recent study year (2019), the utilization rates for non-Hispanic White women compared with non-Hispanic Black/African American women were 23.5 cycles per 10,000 women higher in nonmandated states and 56.2 cycles per 10,000 women higher in mandated states. There was no significant interaction between race and ethnicity and insurance mandate status on any of the clinical outcomes (all P-values for interaction terms > .05). CONCLUSION: Racial and ethnic disparities in utilization of in vitro fertilization and clinical outcomes for autologous cycles persist regardless of state health insurance mandates.

The association between season, day length, and temperature on clinical outcomes after cryopreserved embryo transfer.

OBJECTIVE: To investigate whether there is an association between season, temperature, and day length at oocyte retrieval and/or embryo transfer (ET) and clinical outcomes in frozen ET cycles. DESIGN: Retrospective cohort study. SETTING: Large academically affiliated research hospital. PATIENT(S): A total of 3,004 frozen ET cycles from 1,937 different women with oocyte retrieval and transfer between 2012 and 2017. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation, clinical pregnancy, spontaneous abortion, and live birth. RESULT(S): Frozen ETs with oocyte retrieval dates in summer had 45% greater odds of clinical pregnancy (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.15-1.82) and 42% greater odds of live birth (OR, 1.42; 95% CI, 1.13-1.79) compared with those with oocyte retrieval dates in winter. A 41% greater odds of clinical pregnancy (OR, 1.41; 95% CI, 1.16-1.71) and 34% greater odds of live birth (OR, 1.34; 95% CI, 1.10-1.62) were observed among transfers with an average temperature at oocyte retrieval in the highest tertile (17.2-33.3 °C) compared with those in the lowest tertile (-17.2-6.7 °C). There were no consistent associations between clinical outcomes and day length at oocyte retrieval or between season, day length, or temperature at transfer of thawed embryos. CONCLUSION(S): Warmer temperatures at oocyte retrieval are associated with higher odds of clinical pregnancy and live birth among frozen ET cycles. The consistent associations seen with oocyte retrieval dates and the lack of associations observed with ET dates suggest that any seasonality effects on in vitro fertilization success are related to ovarian function and not uterine receptivity.

Seasonal variation, temperature, day length, and IVF outcomes from fresh cycles.

PURPOSE: It is known that delivery rates from spontaneous conception vary according to season which may be due to cultural or environmental factors; however, conflicting data exist regarding whether outcomes from IVF are also seasonally dependent. The present study was designed to test the hypothesis that the season at oocyte retrieval is associated with livebirth after fresh transfer. METHODS: Dates of oocyte retrieval for all autologous cycles in our IVF program between January 2012 and December 2017 were categorized by season. Dates were linked to local temperature (min, max, average) and day length obtained from meteorological records. Average maximum temperature and day length were categorized into tertiles. Multivariable logistic regression, adjusted for age and quadratic age, were used to model odds (aOR) of implantation, clinical pregnancy, spontaneous abortion, and livebirth. RESULTS: Patient characteristics were similar across seasons. As expected, temperature and day length varied by season. When compared with cycles started during winter, there was no difference in the age-adjusted odds of livebirth for the other three seasons (spring: aOR: 0.97, 95% CI: 0.82-1.13; summer: aOR: 1.05, 0.90-1.23; fall: aOR: 0.98, 0.84-1.15). There was a positive linear trend between temperature and odds of implantation, and clinical pregnancy (p value, test for linear trend (implantation, p = 0.02; clinical pregnancy, p = 0.01)) but no association with livebirth for temperature or day length. CONCLUSIONS: We found that season at oocyte retrieval was not associated with livebirth, contrary to patterns seen in naturally conceived populations. However, our data did suggest modestly higher odds of clinical pregnancy for retrievals in June and July, and that higher temperature at time of retrieval was associated with higher odds of clinical pregnancy but not livebirth.

Choice of statistical model in observational studies of ART.

Analyzing data on ART presents unique and sometimes complicated challenges related to choosing the unit(s) of analysis and the statistical model. In this commentary, we provide examples of how these challenges arise and guidance for overcoming them. We discuss the implications of different ways to count treatment cycles, considering the perspectives of research questions, data management and analysis and patient counseling. We present the advantages and disadvantages of different statistical models, and finally, we discuss the definition and calculation of the cumulative incidence of live birth, which is a key outcome of research on ART.

The importance of mediation in reproductive health studies.

A mediator is a factor that occurs after the exposure of interest, precedes the outcome of interest (i.e. between the exposure and the outcome) and is associated with both the exposure and the outcome of interest (i.e. is on the pathway between exposure and outcome). Mediation analyses can be valuable in many reproductive health contexts, as mediation analysis can help researchers to better identify, quantify and understand the underlying pathways of the association they are studying. The purpose of this commentary is to introduce the concept of mediation and provide examples that solidify understanding of mediation for valid discovery and interpretation in the field of reproductive medicine.

Association of maternal antiretroviral use with microcephaly in children who are HIV-exposed but uninfected (SMARTT): a prospective cohort study.

BACKGROUND: Perinatal HIV transmission has substantially decreased with combination antiretroviral regimens, but complications in children who are HIV-exposed but uninfected, such as microcephaly, warrant ongoing surveillance. We aimed to evaluate whether individual in utero antiretroviral exposures were associated with increased risk of microcephaly based on long-term follow-up of infants and children who are HIV-exposed but uninfected. METHODS: We evaluated children aged younger than 18 years who were HIV-exposed but uninfected with at least one head circumference measurement while enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study at 22 clinical sites in the USA, including Puerto Rico. This prospective cohort study was done by the Pediatric HIV/AIDS Cohort Study network. Microcephaly was defined as having a head circumference Z score <-2 according to the 2000 US Centers for Disease Control and Prevention growth charts for children 6-36 months old and according to Nellhaus standards (head circumference <2nd percentile) after 36 months (SMARTT criteria); an alternate definition for microcephaly was based on applying Nellhaus standards across all ages (Nellhaus criteria). Modified Poisson regression models were fit to obtain relative risks (RRs) for associations between in utero antiretroviral exposure and microcephaly status, adjusted for potential confounders. Neurodevelopmental functioning was compared in children who are HIV-exposed but uninfected with or without microcephaly. FINDINGS: Between March 21, 2007, and Aug 1, 2017, 3055 participants enrolled in SMARTT had at least one head circumference measurement. The cumulative incidence of microcephaly over a median of 5·1 years of follow-up (IQR 3·0-7·2) was 159 (5·2%, 95% CI 4·4-6·1) by Nellhaus criteria and 70 (2·3%, 1·8-2·9) by SMARTT criteria. In adjusted models, in utero exposure to efavirenz (4·7% exposed) was associated with increased risk of microcephaly by both Nellhaus standards (adjusted RR 2·02, 95% CI 1·16-3·51) and SMARTT criteria (2·56, 1·22-5·37). These associations were more pronounced in children exposed to combination regimens of efavirenz that included zidovudine plus lamivudine than those including tenofovir plus emtricitabine. Protective associations were observed for darunavir exposure (adjusted RR 0·50, 95% CI 0·24-1·00). Children who are HIV-exposed but uninfected with microcephaly had lower mean scores on neurodevelopmental assessments at age 1 and 5 years and a higher prevalence of neurodevelopmental impairment than those without microcephaly. INTERPRETATION: These findings support consideration of alternatives to efavirenz as part of first-line antiretroviral therapy for pregnant women. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Gestational carrier in assisted reproductive technology.

OBJECTIVE: To compare clinical outcomes of in vitro fertilization (IVF) cycles with the use of gestational carriers (GCs) with non-GC IVF cycles. DESIGN: Retrospective cohort study of assisted reproductive technology (ART) cycles performed with (24,269) and without (1,313,452) the use of a GC. SETTING: ART centers. PATIENT(S): Infertile patients seeking IVF with or without use of a GC. INTERVENTIONS(S): Autologous and donor oocyte cycles, fresh and cryopreserved embryo transfer cycles. MAIN OUTCOME MEASURE(S): Live birth rate (LBR), twin and high-order multiple birth rates. RESULT(S): Approximately 2% of embryo transfers used a GC. Per embryo transfer, GCs had greater pregnancy rate and LBR across all IVF types compared with non-GC cycles in crude models and models adjusted a priori for potential confounders. For women with uterine-factor infertility, embryo transfer with the use of a GC resulted in a higher odds of live birth for autologous fresh embryos and for cryopreserved embryos compared with patients with non-uterine-factor infertility diagnoses. CONCLUSION(S): GC benefits LBRs for some patients seeking ART. The highest LBRs occurred when the indication for GC was uterine-factor infertility.

Evaluating effects of prenatal exposure to phthalate mixtures on birth weight: A comparison of three statistical approaches.

OBJECTIVES: We applied three statistical approaches for evaluating associations between prenatal urinary concentrations of a mixture of phthalate metabolites and birth weight. METHODS: We included 300 women who provided 732 urine samples during pregnancy and delivered a singleton infant. We measured urinary concentrations of metabolites of di(2-ethylhexyl)-phthalate, di-isobutyl-, di-n-butyl-, butylbenzyl-, and diethyl phthalates. We applied 1) linear regressions; 2) classification methods [principal component analysis (PCA) and structural equation models (SEM)]; and 3) Bayesian kernel machine regression (BKMR), to evaluate associations between phthalate metabolite mixtures and birth weight adjusting for potential confounders. Data were presented as mean differences (95% CI) in birth weight (grams) as each phthalate increased from the 10th to the 90th percentile. RESULTS: When analyzing individual phthalate metabolites using linear regressions, each metabolite demonstrated a modest inverse association with birth weight [from -93 (-206, 21) to -49 (-164, 65)]. When simultaneously including all metabolites in a multivariable model, inflation of the estimates and standard errors were noted. PCA identified two principal components, both inversely associated with birth weight [-23 (-68, 22), -27 (-71, 17), respectively]. These inverse associations were confirmed when applying SEM. BKMR further identified that monoethyl and mono(2-ethylhexyl) phthalate and phthalate concentrations were linearly related to lower birth weight [-51(-164, 63) and -122 (-311, 67), respectively], and suggested no evidence of interaction between metabolites. CONCLUSIONS: While none of the methods produced significant results, we demonstrated the potential issues arising using linear regression models in the context of correlated exposures. Among the other selected approaches, classification techniques identified common sources of exposures with implications for interventions, while BKMR further identified specific contributions of individual metabolites.

Contributions of Disease Severity, Psychosocial Factors, and Cognition to Behavioral Functioning in US Youth Perinatally Exposed to HIV.

Among perinatally HIV-infected (PHIV) and perinatally HIV-exposed, uninfected (PHEU) youth, we evaluated the contributions of home environment, psychosocial, and demographic factors and, among PHIV only, HIV disease severity and antiretroviral treatment (ART), to cognitive functioning (CF) and behavioral functioning (BF). A structural equation modeling (SEM) approach was utilized. Exploratory factor analysis was used to reduce predictor variables to major latent factors. SEMs were developed to measure associations between the latent factors and CF and BF outcomes. Participants included 231 PHIV and 151 PHEU youth (mean age = 10.9 years) enrolled in the PHACS adolescent master protocol. Youth and caregivers completed assessments of CF, BF, psychosocial factors and HIV health. Medical data were also collected. Clusters of predictors were identified, establishing four parsimonious SEMs: child-assessed and caregiver-assessed BF in PHIV and PHEU youth. Among both groups, higher caregiver-child stress predicted worse BF. Caregiver resources and two disease severity variables, late presenter and better past HIV health, were significant predictors of CF in PHIV youth. Higher youth CF was associated with better caregiver-reported BF in both groups. Caregiver resources predicted caregiver-reported BF in PHEU youth, which was mediated via youth CF. Among PHIV youth, better past HIV health and caregiver resources mediated the effects of CF on caregiver-assessed BF. Using SEMs, we found a deleterious impact of caregiver and child stress on BF in both groups and of HIV disease factors on the CF of PHIV youth, reinforcing the importance of early comprehensive intervention to reduce risks for impairment.

Who receives a medical evaluation for infertility in the United States?

OBJECTIVE: To investigate characteristics of receiving a medical evaluation for infertility among infertile women. DESIGN: Prospective cohort. SETTING: Academic institution. PATIENT(S): A total of 7,422 women who reported incident infertility between 1989 and 2009 in the Nurses' Health Study II. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Report of receiving a medical evaluation for infertility. RESULT(S): Approximately 65% of women who reported infertility had a medical evaluation for infertility. Infertile women who were parous (relative risk [RR] = 0.81, 95% confidence interval [CI] 0.78-0.84), older, current smokers (RR = 0.89, 95% CI 0.83-0.96), or who had a higher body mass index (BMI) were less likely to report receiving a medical infertility evaluation. Infertile women who exercised frequently, took multivitamins (RR = 1.03, 95% CI 1.00-1.07), lived in states with comprehensive insurance coverage (RR = 1.09, 95% CI 1.00-1.19), had a high household income, or who had a recent physical examination (RR = 1.15, 95% CI 1.06-1.24) were more likely to report receiving a medical infertility evaluation. CONCLUSION(S): These findings highlight demographic, lifestyle, and access barriers to receiving medical infertility care. Historically, the discussion of barriers to infertility care has centered on financial access, geographic access, and socioeconomic status. Our findings build off literature by supporting previously reported associations and showcasing the importance of demographic and lifestyle factors in accessing care.

Lifestyle and in vitro fertilization: what do patients believe?

BACKGROUND: Patients have many beliefs regarding lifestyle factors and IVF outcomes. METHODS: Observational study of 208 IVF patients at an academic infertility center. Main outcome measures were perceived influence of various lifestyle factors assessed by multivariable logistic regression and p-value tests for linear trend (Pt). RESULTS: A majority of participants believed that there were many women's lifestyle choices that were influential, compared to fewer male factors (cessation of tobacco (72 %), alcohol (69 %), caffeine (62 %), and use of vitamins (88 %)). Compared to participants with less education, participants with a higher education level were less likely to believe vitamins were helpful and some alcohol use was not harmful. As income decreased, participants were less likely to consider dietary factors contributory to IVF success, such as women (p-trend, p = 0.02) and men (p-trend, p = 0.009) consuming a full-fat dairy diet. Participants' beliefs were most commonly influenced by physicians (84 %) and the internet (71 %). CONCLUSIONS: Patients believed many lifestyle factors are associated with IVF success. Understanding patients' assumptions regarding the effect of lifestyle factors on IVF success may better allow physicians to counsel patients about IVF outcomes.

Factors associated with second-trimester pregnancy loss in women with normal uterine anatomy undergoing in vitro fertilization.

OBJECTIVE: To evaluate factors associated with second-trimester pregnancy loss in patients with normal uterine anatomy who conceived through in vitro fertilization. METHODS: Women aged 21-44 years with ongoing in vitro fertilization pregnancy (at least one fetus with fetal heart tones at 12 weeks of gestation) at an academic hospital from 2001 to 2012 were eligible for inclusion in this retrospective cohort. Comprehensive uterine evaluation permitted inclusion of only women with anatomically normal uterine cavities. Maternal and clinical characteristics associated with spontaneous second-trimester pregnancy loss (between 12 1/7 and 23 6/7 weeks of gestation) were assessed. Multivariable logistic regression generated adjusted odds ratios (ORs), 95% confidence intervals (CIs), and Wald two-sided P values. RESULTS: Among ongoing second-trimester pregnancies, 60 (2.1%) ended in spontaneous pregnancy loss and 2,841 (97.9%) ended in live birth. Multiple gestations (twins or more) conferred greater odds of pregnancy loss (adjusted OR 1.93, CI 1.15-3.24, P=.01) and were more prevalent among losses (48.3%) than live births (34.1%). Uterine leiomyomas were present in 16.7% of losses and 4.7% of live births and were associated with a nearly fourfold increased odds of second-trimester pregnancy loss (adjusted OR 3.82, CI 1.85-7.89, P<.001). Women with obese body mass index ([BMI] 30 or higher) at cycle start experienced twofold greater odds of pregnancy loss compared with normal-weight women (adjusted OR 2.38, CI 1.05-5.65, P=.04). There were eight obese women (32%) among losses and 209 obese women (16.5%) among live births. In vitro fertilization treatment parameters were not associated with odds of second-trimester loss nor were maternal age, ethnicity, or history of recurrent pregnancy loss. CONCLUSION: Odds of second-trimester spontaneous pregnancy loss among in vitro fertilization conceived pregnancies were greater with multiple gestations, leiomyomas, and obese maternal BMI. LEVEL OF EVIDENCE: II.

Serum progesterone concentration on day of embryo transfer in donor oocyte cycles.

PURPOSE: To evaluate the association between serum progesterone (P) levels on the day of embryo transfer (ET) and pregnancy rates in fresh donor IVF/ICSI cycles. METHODS: Fresh donor cycles with day 3 ET from 10/2007 to 8/2012 were included (n = 229). Most cycles (93 %) were programmed with a gonadotropin releasing hormone (GnRH) agonist; oral, vaginal or transdermal estradiol was used for endometrial priming, and intramuscular P was used for luteal support (50-100 mg/day). Recipient P levels were measured at ET, and P dose was increased by 50-100 % if <20 ng/mL per clinic practice. The main outcome measure was rate of live birth (> = 24 weeks gestational age). Generalized estimating equations were used to account for multiple cycles from the same recipient, adjusted a priori for recipient and donor age. RESULTS: Mean recipient serum P at ET was 25.5 ± 10.1 ng/mL. Recipients with P < 20 ng/mL at ET, despite P dose increases after ET, were less likely to achieve clinical pregnancy (RR = 0.75, 95 % CI = 0.60-0.94, p = 0.01) and live birth (RR = 0.77, 95 % CI = 0.60-0.98, p = 0.04), as compared to those with P ≥ 20 ng/mL. P dose increases were more often required in overweight and obese recipients. CONCLUSIONS: Serum P levels on the day of ET in fresh donor IVF/ICSI cycles were positively correlated with clinical pregnancy and live birth rates. An increase in P dose after ET was insufficient to rescue pregnancy rates. Overweight and obese recipients may require higher initial doses of P supplementation. Future research is needed to define optimal serum P at ET and the interventions to achieve this target.

Effect of body mass index on in vitro fertilization outcomes in women with polycystic ovary syndrome.

OBJECTIVE: The objective of the investigation was to study the effect of body mass index (BMI) on in vitro fertilization (IVF) outcomes within a polycystic ovary syndrome (PCOS) population. STUDY DESIGN: This was a retrospective cohort study including 101 cycles from 79 women younger than 40 years old with a clinically documented diagnosis of PCOS by Rotterdam criteria undergoing IVF at a university-based infertility clinic from 2001 through 2010. All participants were stratified by BMI calculated from height and weight recorded within 3 months of cycle start: lean (18.7-24.9 kg/m(2), n = 51), overweight (25-29.9 kg/m(2), n = 19), and obese (≥30 kg/m(2), n = 31). Linear, logistic, and Poisson regressions were used as appropriate to estimate the effect of a range of BMIs on IVF outcomes while adjusting for potential confounders. RESULTS: Obese PCOS women had 69% lower odds of clinical pregnancy per cycle start (odds ratio [OR], 0.31; 95% confidence interval [CI], 0.11-0.86; P = .02) and 77% lower odds of clinical pregnancy per embryo transfer (OR, 0.23; 95% CI, -0.08 to 0.68; P = .008) compared with lean PCOS women. Among obese PCOS women, the odds of live birth were 71% lower per cycle start (OR, 0.29; 95% CI, 0.10-0.84; P = .02) and 77% lower per embryo transfer (OR, 0.23; 95% CI, 0.07-0.71; P = .01) compared with lean PCOS women. There was a trend toward decreased ovarian hyperstimulation syndrome incidence with increasing BMI among women with PCOS: 19.6% in lean, 10.5% in overweight, and 3.2% in obese. CONCLUSION: PCOS is a broad syndrome, with our results demonstrating 2 distinct populations, lean and obese, which have different IVF outcomes including ovarian hyperstimulation syndrome risk profiles. This information is important for clinicians because it informs treatment decisions.

Pharmacokinetics of human chorionic gonadotropin injection in obese and normal-weight women.

CONTEXT: Obese women have poorer in vitro fertilization outcomes, but underlying mechanisms remain unclear. OBJECTIVE: The objectives of the study were to compare the pharmacokinetics of human chorionic gonadotropin (hCG) and ovarian steroid hormone production, after subcutaneous (s.c.) and intramuscular (i.m.) injection of hCG in obese and normal-weight women. DESIGN AND SETTING: This was a randomized, experimental study. PATIENTS OR OTHER PARTICIPANTS: Twenty-two women aged 18-42 years with body mass index of 18.5-24.9 (normal) or 30-40 kg/m(2) (obese). INTERVENTIONS: Participants received im urinary hCG or s.c. recombinant hCG and returned for a second injection type after a 4-week washout. Intramuscular injections were performed under ultrasound guidance. Blood was taken 0, 0.5, 1, 2, 4, 6, 8, 12, 24, and 36 hours after injection. MAIN OUTCOME MEASURES: hCG was measured at each time point; estradiol, progesterone, 17-hydroxyprogesterone (17-OHP), testosterone (T), dehydroepiandrosterone, and SHBG were measured at 0 and 36 hours. RESULTS: Twenty-two women completed the study. In both normal-weight and obese women, peak serum concentration (Cmax), area under the curve (AUC), and average hCG concentration were higher after i.m. injection as compared with s.c. injection (all P < .003). Obese women had markedly lower Cmax, AUC, and average hCG concentration after s.c. injection as compared with normal-weight women (P = .02, P = .009, and P = .008, respectively). After i.m. injection, Cmax, AUC, and average concentration were similar for normal-weight and obese women (P = .31, P = .25, and P = .18, respectively). Thirty-six percent of obese women had muscular layers beyond the reach of a standard 1.5 inch needle. hCG caused a significant rise in 17-OHP in both obese and normal-weight women and an increase in T in obese but not normal-weight women (all P < .04). CONCLUSIONS: Subcutaneous injection yields lower hCG levels in obese women. Standard-length needles are insufficient to administer i.m. injections in many obese women.