Polycystic ovary syndrome and risk of adverse pregnancy outcomes: a registry linkage study from Massachusetts.

STUDY QUESTION: Do women with polycystic ovary syndrome (PCOS) have a greater risk of adverse pregnancy complications (gestational diabetes, preeclampsia, cesarean section, placental abnormalities) and neonatal outcomes (preterm birth, small for gestational age, prolonged delivery hospitalization) compared to women without a PCOS diagnosis and does this risk vary by BMI, subfertility and fertility treatment utilization? SUMMARY ANSWER: Deliveries to women with a history of PCOS were at greater risk of complications associated with cardiometabolic function, including gestational diabetes and preeclampsia, as well as preterm birth and prolonged length of delivery hospitalization. WHAT IS KNOWN ALREADY: Prior research has suggested that women with PCOS may be at increased risk of adverse pregnancy outcomes. However, findings have been inconsistent possibly due to lack of consistent adjustment for confounding factors, small samples size and other sources of bias. STUDY DESIGN, SIZE, DURATION: Massachusetts deliveries among women ≥18 years old during 2013-2017 from state vital records linked to hospital discharges, observational stays and emergency department visits were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) and the Massachusetts All-Payers Claims Database (APCD). PARTICIPANTS/MATERIALS, SETTING, METHODS: PCOS was identified by ICD9 and ICD10 codes in APCD prior to index delivery. Relative risks (RRs) and 95% CI for pregnancy and delivery complications were modeled using generalized estimating equations with a log link and a Poisson distribution to take multiple cycles into account and were adjusted a priori for maternal age, BMI, race/ethnicity, education, plurality, birth year, chronic hypertension and chronic diabetes. Tests for homogeneity investigated differences between maternal pre-pregnancy BMI categories (<30, ≥30, <25 and ≥25 kg/m2) and between non-infertile deliveries and deliveries that used ART or had a history of subfertility (defined by birth certificates, SART CORS records, APCD or hospital records). MAIN RESULTS AND THE ROLE OF CHANCE: Among 91 825 deliveries, 3.9% had a history of PCOS. Women with a history of PCOS had a 51% greater risk of gestational diabetes (CI: 1.38-1.65) and a 25% greater risk of preeclampsia (CI: 1.15-1.35) compared to women without a diagnosis of PCOS. Neonates born to women with a history of PCOS were more likely to be born preterm (RR: 1.17, CI: 1.06-1.29) and more likely to have a prolonged delivery hospitalization after additionally adjusting for gestational age (RR: 1.23, CI: 1.09-1.40) compared to those of women without a diagnosis of PCOS. The risk for gestational diabetes for women with PCOS was greater among women with a pre-pregnancy BMI <30 kg/m2. LIMITATIONS, REASONS FOR CAUTION: PCOS was defined by ICD documentation prior to delivery so there may be women with undiagnosed PCOS or PCOS diagnosed after delivery included in the unexposed group. The study population is limited to deliveries within Massachusetts among most private insurance payers and inpatient or observational hospitalization in Massachusetts during the follow-up window, therefore there may be diagnoses and or deliveries outside of the state or outside of our sample that were not captured. WIDER IMPLICATIONS OF THE FINDINGS: In this population-based study, women with a history of PCOS were at greater risk of pregnancy complications associated with cardiometabolic function and preterm birth. Obstetricians should be aware of patients' PCOS status and closely monitor for potential pregnancy complications to improve maternal and infant perinatal health outcomes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the NIH (R01HD067270). S.A.M. receives grant funding from NIH, AbbVie and the Marriot Family Foundation; payment/honoraria from the University of British Columbia, World Endometriosis Research Foundation and Huilun Shanghai; travel support for attending meetings for ESHRE 2019, IASP 2019, National Endometriosis Network UK meeting 2019; SRI 2022, ESHRE 2022; participates on the data safety monitoring board/advisory board for AbbVie, Roche, Frontiers in Reproductive Health; and has a leadership role in the Society for Women's Health Research, World Endometriosis Research Foundation, World Endometriosis Society, American Society for Reproductive Medicine and ESHRE. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Pregnancy outcomes among women with endometriosis and fibroids: registry linkage study in Massachusetts.

BACKGROUND: Endometriosis and uterine fibroids are common gynecologic conditions associated with a greater risk for infertility. Previous research has suggested that these conditions are associated with adverse pregnancy outcomes, potentially because of increased utilization of fertility treatments. OBJECTIVE: Our objective was to investigate whether women with a history of endometriosis or fibroids had a greater risk for adverse pregnancy outcomes and whether this risk varied by infertility history and fertility treatment utilization. STUDY DESIGN: Deliveries (2013-2017) recorded in Massachusetts' vital records were linked to assisted reproductive technology data, hospital stays, and all-payer claims database. We identified endometriosis and fibroids diagnoses via the all-payer claims database before index delivery. Adjusted relative risks for pregnancy complications were modeled using generalized estimating equations with a log link and Poisson distribution. The influence of subfertility or infertility and assisted reproductive technology was also investigated. RESULTS: Among 91,825 deliveries, 1560 women had endometriosis and 4212 had fibroids. Approximately 30% of women with endometriosis and 26% of women with fibroids experienced subfertility or infertility without utilizing assisted reproductive technology, and 34% of women with endometriosis and 21% of women with fibroids utilized assisted reproductive technology for the index delivery. Women with a history of endometriosis or fibroids were at a greater risk for pregnancy-induced hypertension, preeclampsia, or eclampsia (endometriosis relative risk, 1.17; fibroids relative risk, 1.08), placental abnormalities (endometriosis relative risk, 1.65; fibroids relative risk, 1.38), and cesarean delivery (endometriosis relative risk, 1.22; fibroids relative risk, 1.17) than women with no history of those conditions. Neonates born to women with a history of endometriosis or fibroids were also at a greater risk for preterm birth (endometriosis relative risk, 1.24; fibroids relative risk, 1.17). Associations between fibroids and low birthweight varied by fertility status or assisted reproductive technology (P homogeneity=.01) and were stronger among noninfertile women. CONCLUSION: Endometriosis or fibroids increased the risk for adverse pregnancy outcomes, possibly warranting differential screening or treatment.

History of cancer and fertility treatment outcomes: a registry linkage study in Massachusetts.

PURPOSE: To investigate assisted reproductive technology (ART) outcomes among adolescent and young-adult female cancer survivors. METHODS: The Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) data were linked to the Massachusetts Cancer Registry for 90,928 ART cycles in Massachusetts to women ≥ 18 years old from 2004 to 2013. To estimate relative risks (RR) and 95% confidence intervals (CI), we used generalized estimating equations with a log link that accounted for multiple cycles per woman and a priori adjusted for maternal age and cycle year. The main outcomes of interest were ART treatment patterns; number of autologous oocytes retrieved, fertilized, and transferred; and rates of implantation, clinical intrauterine gestation (CIG), live birth, and pregnancy loss. RESULTS: We saw no difference in number of oocytes retrieved (aRR: 0.95 (0.89-1.02)) or proportion of autologous oocytes fertilized (aRR: 0.99 (0.95-1.03)) between autologous cycles with and without a history of cancer; however, cancer survivors required a higher total FSH administered (aRR: 1.12 (1.06-1.19)). Among autologous cycle starts, cycles in women with a history of cancer were less likely to result in CIG compared to no history of cancer (aRR: 0.73 (0.65-0.83)); this relationship was absent from donor cycles (aRR: 1.01 (0.85-1.20)). Once achieving CIG, donor cycles for women with a history of cancer were two times more likely to result in pregnancy loss (aRR: 1.99 (1.26-3.16)). CONCLUSIONS: Our analysis suggests that cancer may influence ovarian stimulation response, requiring more FSH and resulting in lower CIG among cycle starts.

Early-life cancer, infertility, and risk of adverse pregnancy outcomes: a registry linkage study in Massachusetts.

PURPOSE: Investigate the relationship between history of cancer and adverse pregnancy outcomes according to subfertility/fertility treatment. METHODS: Deliveries (2004-2013) from Massachusetts (MA) Registry of Vital Records and Statistics were linked to MA assisted reproductive technology data, hospital discharge records, and Cancer Registry. The relative risks (RR) and 95% confidence intervals of adverse outcomes (gestational diabetes (GDM), gestational hypertension (GHTN), cesarean section (CS), low birth weight (LBW), small for gestational age (SGA), preterm birth (PTB), neonatal mortality, and prolonged neonatal hospital stay) were modeled with log-link and Poisson distribution generalized estimating equations. Differences by history of subfertility/fertility treatment were investigated with likelihood ratio tests. RESULTS: Among 662,630 deliveries, 2,983 had a history of cancer. Women with cancer history were not at greater risk of GDM, GHTN, or CS. However, infants born to women with prior cancer had higher risk of LBW (RR: 1.19 [1.07-1.32]), prolonged neonatal hospital stay (RR: 1.16 [1.01-1.34]), and PTB (RR: 1.19 [1.07-1.32]). We found clinically and statistically significant differences in the relationship between cancer history and SGA by subfertility/fertility treatment (p value, test for heterogeneity = 0.02); among deliveries with subfertility or fertility treatment, those with a history of cancer experienced a greater risk of SGA (RRsubfertile: 1.36 [1.02-1.83]). CONCLUSIONS: Women with a history of cancer had greater risk of some adverse pregnancy outcomes; this relationship varied by subfertility and fertility treatment.

Embryo biopsy and maternal and neonatal outcomes following cryopreserved-thawed single embryo transfer.

BACKGROUND: Contemporary embryo biopsy in the United States involves the removal of several cells from a blastocyst that would become the placenta for preimplantation genetic testing. Embryos are then cryopreserved while patients await biopsy results, with transfers occurring in a subsequent cycle as a single frozen-thawed embryo transfer, if euploid. OBJECTIVE: We sought to determine if removal of these cells for preimplantation genetic testing was associated with adverse obstetrical or neonatal outcomes after frozen-thawed single embryo transfer. STUDY DESIGN: We linked assisted reproductive technology surveillance data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System to birth certificates and maternal and neonatal hospitalization discharge diagnoses in Massachusetts from 2014 to 2017, considering only singleton births after frozen-thawed single embryo transfers. We compared outcomes of cycles having embryo biopsy (n=585) to those having no biopsy (n=2191) using chi-square for categorical and binary variables and logistic regression for adjusted odds ratios and 95% confidence intervals, adjusting for mother's age, race, education, parity, body mass index, birth year, insurance, and all infertility diagnoses. RESULTS: Considering no biopsy as the reference, there was no difference between groups with respect to preeclampsia (adjusted odds ratio, 0.82; 95% confidence interval, 0.42-1.61; P=.5685); pregnancy-induced hypertension (adjusted odds ratio, 0.85; 95% confidence interval, 0.46-1.59; P=.6146); placental disorders, including placental abruption, placenta previa, placenta accreta, placenta increta, and placenta percreta (adjusted odds ratio, 1.16; 95% confidence interval, 0.60-2.24; P=.6675); preterm birth (adjusted odds ratio, 1.22; 95% confidence interval 0.73-2.03; P=.4418); low birthweight (adjusted odds ratio, 1.12; 95% confidence interval, 0.58-2.15; P=.7355); cesarean delivery (adjusted odds ratio, 1.04; 95% confidence interval, 0.79-1.38; P=.7762); or gestational diabetes mellitus (adjusted odds ratio, 0.83; 95% confidence interval, 0.50-1.38; P=.4734). In addition, there was no difference between the groups for prolonged hospital stay for mothers (adjusted odds ratio, 1.23; 95% confidence interval, 0.83-1.80; P=.3014) or for infants (95% confidence interval, 1.29; 95% confidence interval, 0.72-2.29; P=.3923). CONCLUSION: Embryo biopsy for preimplantation genetic testing does not increase the odds for diagnoses related to placentation (preeclampsia, pregnancy-related hypertension, placental disorders, preterm delivery, or low birthweight), maternal conditions (gestational diabetes mellitus), or maternal or infant length of stay after delivery.

Optimizing the control group for evaluating ART outcomes: can outpatient claims data yield a better control group?

PURPOSE: We previously developed a subfertile comparison group with which to compare outcomes of assisted reproductive technology (ART) treatment. In this study, we evaluated whether insurance claims data in the Massachusetts All Payers Claims Database (APCD) defined a more appropriate comparison group. METHODS: We used Massachusetts vital records of women who delivered between 2013 and 2017 on whom APCD data were available. ART deliveries were those linked to a national ART database. Deliveries were subfertile if fertility treatment was marked on the birth certificate, had prior hospitalization with ICD code for infertility, or prior fertility treatment. An infertile group included women with an APCD outpatient or inpatient ICD 9/10 infertility code prior to delivery. Fertile deliveries were none of the above. Demographics, health risks, and obstetric outcomes were compared among groups. Multivariable generalized estimating equations were used to calculate adjusted relative risk (aRR) and 95% confidence intervals (CI). RESULTS: There were 70,726 fertile, 4,763 subfertile, 11,970 infertile, and 7,689 ART-treated deliveries. Only 3,297 deliveries were identified as both subfertile and infertile. Both subfertile and infertile were older, and had more education, chronic hypertension, and diabetes than the fertile group and less than the ART-treated group. Prematurity (aRR = 1.15-1.17) and birthweight (aRR = 1.10-1.21) were increased in all groups compared with the fertile group. CONCLUSION: Although the APCD allowed identification of more women than the previously defined subfertile categorization and allowed us to remove previously unidentified infertile women from the fertile group, it is not clear that it offered a clinically significantly improved comparison group.

Utilization and Outcomes of Fertility Preservation Techniques in Women Undergoing Allogeneic Hematopoietic Cell Transplant.

Iatrogenic menopause with consequent infertility is a major complication in reproductive-age women undergoing hematopoietic cell transplantation (HCT). Recent guidelines recommend a discussion of the possibility of infertility and the options for fertility preservation as part of informed consent before initiation of any cancer-directed therapy, including HCT. Women age 15 to 49 years at the time of allogeneic HCT, between the years 2001 and 2017, were identified from the Mayo Clinic Rochester institutional HCT database. One hundred seventy-seven women were eligible, of whom 49 (28%) were excluded due to documented postmenopausal state or prior hysterectomy. The median age of the cohort was 31 years (range, 15 to 49 years) with median gravidity and parity being G1P1 (range, G0 to G8, P0 to P6). Fifty-four (42%) women were nulligravid at the time of HCT. Eighty-two percent underwent myeloablative conditioning (MAC), whereas 18% underwent reduced-intensity conditioning (RIC). Only 34 women (27%) had documented fertility counseling within 72 hours of diagnosis, and a total of 61 (48%) received fertility counseling prior to HCT. Thirty-eight women (30%) were referred to a reproductive endocrinologist, of whom 13 (10%) underwent assisted reproductive technologies (ART; nine oocyte cryopreservation, four embryo cryopreservation). Of these, nine procedures yielded successful cryopreserved tissue (two completed at outside institutions). The median time to completion of the seven successful ART procedures at Mayo Clinic was 13 days (range, 9 to 15 days). The remainder of women referred to reproductive endocrinology did not undergo ART due to disease severity (68%), financial barriers (20%), and/or low antral follicle count (12%). Ninety-three women (73%) received leuprolide for ovarian suppression prior to conditioning. Three (4%) of 75 women who underwent MAC and were alive >365 days after HCT had spontaneous menstrual recovery after HCT (median time, 14 months; range, 6 to 21 months), in comparison to 10 (50%) of 20 women who underwent RIC and were alive >365 days after HCT (P < .01) (median, 21.5 months; range, 5 to 83 months). In the latter cohort, there were two spontaneous pregnancies, occurring at 71 and 72 months after HCT, respectively. Oncofertility is an emerging field due to an increasing number of young cancer survivors. Herein, we document that even at a large tertiary HCT center, the rate of documented fertility counseling and reproductive endocrinology referrals was low and the rate of ART was even lower. Spontaneous menstrual recovery was rare but more likely in the setting of nonmalignant disease and RIC HCT. A concerted multidisciplinary effort is needed to understand parenthood goals and to explore the impact of HCT on decision making about fertility preservation and parenthood. These efforts could improve oncofertility referral, ART utilization, and reproductive outcomes.

Hospitalization before and after delivery in fertile, subfertile, and ART-treated women.

PURPOSE: Pre-pregnancy and post-delivery hospitalizations were compared as markers for health among women who conceived using assisted reproductive technology (ART), non-ART medically assisted reproduction (MAR), no treatment (unassisted subfertile), and who were fertile. METHODS: We analyzed hospital discharge data linked to Massachusetts birth certificates from 2004 to 2013 within 5 years prior to pregnancy and 8-365 days post-delivery. ART deliveries were linked from a national ART database; MAR deliveries had fertility treatment but not ART; unassisted subfertile women had subfertility but no ART or MAR; and fertile women had none of these. Prevalence of diagnoses during hospitalization was quantified. Multivariable logistic regression models with fertile deliveries as reference were adjusted for maternal age, race, education, year, and plurality (post-delivery only) with results reported as adjusted odds ratios (AORs) and 95% confidence intervals (CI). RESULTS: Of 170,605 privately insured, primiparous deliveries, 10,458 were ART, 3005 MAR, 1365 unassisted subfertile, and 155,777 fertile. Pre-pregnancy hospitalization occurred in 6.8% and post-delivery in 2.8% of fertile women. Subfertile groups had more pre-pregnancy hospitalizations (AOR, 95% CI: 1.84, 1.72-1.96 ART; 1.41, 1.24-1.60 MAR; 3.02, 2.62-3.47 unassisted subfertile) with endometriosis, reproductive organ disease, ectopic pregnancy/miscarriage, and disorders of menstruation, ovulation, and genital tract being common. Post-delivery hospitalizations were significantly more frequent in the ART (AOR 1.19, 95% CI 1.05-1.34) and unassisted subfertile (1.59, 1.23-2.07) groups with more digestive tract disorders, thyroid problems, and other grouped chronic disease conditions. CONCLUSIONS: Greater likelihood of hospitalization in the ART, MAR, and unassisted subfertile groups is largely explained by admissions for conditions associated with subfertility.

Birth outcomes of singleton vaginal deliveries to ART-treated, subfertile, and fertile primiparous women.

PURPOSE: To determine whether differences in birth outcomes among assisted reproductive technology (ART)-treated, subfertile, and fertile women exist in primiparous women with, singleton, vaginal deliveries. METHODS: Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) data were linked to Massachusetts vital records and hospital discharges for deliveries between July 2004 and December 2010. Primiparous women with in-state vaginal deliveries, adequate prenatal care, and singleton birth at ≥ 20 weeks (n = 117,779) were classified as ART-treated (linked to ART data from SART CORS, n = 3138); subfertile (not ART-treated but with indicators of subfertility, n = 1507); or fertile (neither ART-treated nor subfertile, n = 113,134). Outcomes of prematurity (< 37 weeks), low birthweight (< 2500 g), perinatal death (death at ≥ 20 weeks to ≤ 7 days), and maternal prolonged length of hospital stay (LOS > 3 days) were compared using multivariable logistic regression. RESULTS: Compared to fertile, higher odds were found for prematurity among ART-treated (adjusted odds ratio [AOR] 1.40, 95% confidence interval [CI] 1.25-1.50) and subfertile (AOR 1.25, 95% CI 1.03-1.50) women, low birthweight among ART-treated (AOR 1.41, 95% CI 1.23-1.62) and subfertile (AOR 1.40, 95% CI 1.15-1.71) women, perinatal death among subfertile (AOR 2.64, 95% CI 1.72-4.05), and prolonged LOS among ART-treated (AOR 1.33, 95% CI 1.19-1.48) women. Differences remained despite stratification by young age and absence of pregnancy/delivery complications. CONCLUSIONS: Greater odds of prematurity and low birthweight in ART-treated and subfertile, and perinatal death in subfertile deliveries are evident among singleton vaginal deliveries. The data suggest that even low-risk pregnancies to ART-treated and subfertile women be managed for adverse outcomes.

Effects of increasing levothyroxine on pregnancy outcomes in women with uncontrolled hypothyroidism.

OBJECTIVE: Uncontrolled hypothyroidism has been associated with an increased risk of adverse pregnancy outcomes. We aimed to assess the effectiveness of increasing levothyroxine (LT4) dose on reducing the risk of adverse outcomes for pregnant women with TSH level greater than the recommended 1st trimester limit. DESIGN, PATIENTS, MEASUREMENTS: We reviewed the electronic medical records of pregnant women evaluated from January 2011 to December 2013, who had history of LT4-treated hypothyroidism and were found to have TSH > 2·5 mIU/l in 1st trimester. Women were divided into two groups: group A - LT4 dose was increased within two weeks from the TSH test, group B - LT4 dose remained stable. We compared the frequency of pregnancy loss (primary outcome) and other prespecified pregnancy-related adverse outcomes between groups. RESULTS: There were 85 women in group A (median TSH: 5·0, interquartile range 3·8-6·8 mIU/l) and 11 women in group B (median TSH: 4·5, interquartile range 3·2-4·9 mIU/l). The groups were not different in baseline clinical and socioeconomic characteristics. The mean interval between TSH test and LT4 dose increase was 4·5 (SD 4·6) days. Pregnancy loss was significantly lower in group A (2/85, 2·4%) vs group B (4/11, 36·4%) (P = 0·001). Other pregnancy-related adverse outcomes were similar between groups. CONCLUSIONS: Increasing LT4 dose for women with uncontrolled hypothyroidism in the 1st trimester of pregnancy was associated with a decreased risk of pregnancy loss. Given the limitations of our study, this association awaits further confirmation from larger studies.

Increased risk of large-for-gestational age birthweight in singleton siblings conceived with in vitro fertilization in frozen versus fresh cycles.

BACKGROUND: Children born from fresh in vitro fertilization (IVF) cycles are at greater risk of being born smaller and earlier, even when limited to singletons; those born from frozen cycles have an increased risk of large-for-gestational age (LGA) birthweight (z-score ≥1.28). This analysis sought to overcome limitations in other studies by using pairs of siblings, and accounting for prior cycle outcomes, maternal characteristics, and embryo state and stage. METHODS: Pairs of singleton births conceived with IVF and born between 2004 and 2013 were identified from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database, matched for embryo stage (blastocyst versus non-blastocyst) and infant gender, categorized by embryo state (fresh versus frozen) in 1st and 2nd births (four groups). RESULTS: The data included 7795 singleton pairs. Birthweight z-scores were 0.00-0.04 and 0.24-0.26 in 1st and 2nd births in fresh cycles, and 0.25-0.34 and 0.50-0.55 in frozen cycles, respectively. LGA was 9.2-9.8 and 14.2-15.4% in 1st and 2nd births in fresh cycles, and 13.1-15.8 and 20.8-21.0% in 1st and 2nd births in frozen cycles. The risk of LGA was increased in frozen cycles (1st births, adjusted odds ratios (AOR) 1.74, 95% CI 1.45, 2.08; and in 2nd births when the 1st birth was not LGA, AOR 1.70, 95% CI 1.46, 1.98 for fresh/frozen and 1.40, 1.11, 1.78 for frozen/frozen). CONCLUSIONS: Our results with siblings indicate that frozen embryo state is associated with an increased risk for LGA. The implications of these findings for childhood health and risk of obesity are unclear, and warrant further investigation.

Inpatient hospitalizations in women with and without assisted reproductive technology live birth.

PURPOSE: The aim of this study is to evaluate frequency of hospitalization before, during, and after assisted reproductive technology (ART) treatment by cycle outcome. METHODS: Six thousand and one hundred thirty women residing in Massachusetts undergoing 17,135 cycles of ART reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SARTCORS) from 2004 to 2011 were linked to hospital discharges and vital records. Women were grouped according to ART treatment cycle outcome as: no pregnancy (n = 1840), one or more pregnancies but no live birth (n = 968), or one or more singleton live births (n = 3322). Hospital delivery discharges during 1998-2011 were categorized as occurring before, during, or after the ART treatment. The most prevalent ICD-9 codes for non-delivery hospital discharges were compared. Groups were compared using chi square test using SAS 9.3 software. RESULTS: The proportion of any hospitalization was 57.0, 58.3, and 91.3% for women with no pregnancy, no live birth, and ART singleton live birth, respectively; the proportion of non-delivery hospitalizations was 30.4, 31.0, and 28.3%, respectively. The non-ART delivery proportion after ART treatment did not differ by group (33.4, 36.2, and 36.9%, respectively, p = 0.17). Most frequent non-delivery diagnoses (including fibroids, obesity, ectopic pregnancy, depression, and endometriosis) also did not differ by group. A secondary analysis limited to only women with no delivery discharges before the first ART cycle showed similar results. CONCLUSIONS: All groups had live birth deliveries during the study period, suggesting an important contribution of non-ART treatment or treatment-independent conception to overall delivery and live births. Hospitalizations not associated with delivery suggested similarity in morbidity for all ART patients regardless of success with ART treatment.

The Aurora A-HP1γ pathway regulates gene expression and mitosis in cells from the sperm lineage.

BACKGROUND: HP1γ, a well-known regulator of gene expression, has been recently identified to be a target of Aurora A, a mitotic kinase which is important for both gametogenesis and embryogenesis. The purpose of this study was to define whether the Aurora A-HP1γ pathway supports cell division of gametes and/or early embryos, using western blot, immunofluorescence, immunohistochemistry, electron microscopy, shRNA-based knockdown, site-directed mutagenesis, and Affymetrix-based genome-wide expression profiles. RESULTS: We find that the form of HP1γ phosphorylated by Aurora A, P-Ser83 HP1γ, is a passenger protein, which localizes to the spermatozoa centriole and axoneme. In addition, disruption in this pathway causes centrosomal abnormalities and aberrations in cell division. Expression profiling of male germ cell lines demonstrates that HP1γ phosphorylation is critical for the regulation of mitosis-associated gene expression networks. In female gametes, we observe that P-Ser83-HP1γ is not present in meiotic centrosomes of M2 oocytes, but after syngamy, it becomes detectable during cleavage divisions, coinciding with early embryonic genome activation. CONCLUSIONS: These results support the idea that phosphorylation of HP1γ by Aurora A plays a role in the regulation of gene expression and mitotic cell division in cells from the sperm lineage and in early embryos. Combined, this data is relevant to better understanding the function of HP1γ in reproductive biology.

Application of a validated prediction model for in vitro fertilization: comparison of live birth rates and multiple birth rates with 1 embryo transferred over 2 cycles vs 2 embryos in 1 cycle.

OBJECTIVE: The purpose of this study was to use a validated prediction model to examine whether single embryo transfer (SET) over 2 cycles results in live birth rates (LBR) comparable with 2 embryos transferred (DET) in 1 cycle and reduces the probability of a multiple birth (ie, multiple birth rate [MBR]). STUDY DESIGN: Prediction models of LBR and MBR for a woman considering assisted reproductive technology developed from linked cycles from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System for 2006-2012 were used to compare SET over 2 cycles with DET in 1 cycle. The prediction model was based on a woman's age, body mass index (BMI), gravidity, previous full-term births, infertility diagnoses, embryo state, number of embryos transferred, and number of cycles. RESULTS: To demonstrate the effect of the number of embryos transferred (1 or 2), the LBRs and MBRs were estimated for women with a single infertility diagnosis (male factor, ovulation disorders, diminished ovarian reserve, and unexplained); nulligravid; BMI of 20, 25, 30, and 35 kg/m2; and ages 25, 35, and 40 years old by cycle (first or second). The cumulative LBR over 2 cycles with SET was similar to or better than the LBR with DET in a single cycle (for example, for women with the diagnosis of ovulation disorders: 35 years old; BMI, 30 kg/m2; 54.4% vs 46.5%; and for women who are 40 years old: BMI, 30 kg/m(2); 31.3% vs 28.9%). The MBR with DET in 1 cycle was 32.8% for women 35 years old and 20.9% for women 40 years old; with SET, the cumulative MBR was 2.7% and 1.6%, respectively. CONCLUSION: The application of this validated predictive model demonstrated that the cumulative LBR is as good as or better with SET over 2 cycles than with DET in 1 cycle, while greatly reducing the probability of a multiple birth.

Screening for Insulin Resistance in Polycystic Ovary Syndrome: Views of Physician Members of the American Society for Reproductive Medicine.

OBJECTIVE: To determine practice patterns for insulin resistance (IR) evaluation and management in women with polycystic: ovary syndrome (PCOS) among physician members of the American Society for Reproductive Medicine (ASRM). STUDY DESIGN: Cross-sectional survey using a web-based questionnaire. RESULTS: A total of 205 members responded. Respondents were board-certified (94%), or board-eligible (6%), in obstetrics and gynecology. Sixty-four percent of the respondents use the Rotterdam 2003 Criteria for a diagnosis of PCOS. Two-thirds (68%) screenfor IR in women with PCOS. Respondents who screen for IR were more likely to also screen for diabetes and impaired glucose tolerance (OR 3.37, 95% CI 1.48-7.21). The 2-hour oral glucose tolerance test with glucose and insulin concentrations was the most common IR screening test used (45%). Metformin therapy was used by 33% of respondents for, "all women with PCOS who have IR." The majority (68%) responded that there is a need for a committee opinion from ASRM on IR testing in PCOS. CONCLUSION: Two-thirds of ASRM physician members surveyed screen women with PCOS for IR in spite of the lack of general consensus on the need for such screening from endocrine societies.

Single-dose intramuscular methotrexate treatment of cervical ectopic pregnancy. A case report.

BACKGROUND: Cervical ectopic pregnancies (CEPs) are increasingly being managed conservatively. However, the efficacy of specific conservative approaches such as the single-dose intramuscular (IM) methotrexate (MTX) therapy has not been evaluated. We reportthe successful management of 2 consecutive CEPs in the same patient with single-dose IM MTX therapy, and review published cases of CEPs treated with a similar regimen, to determine the efficacy of this approach. CASE: In our case, both CEPs resolved with single-dose IM MTX, and the patient subsequently had a successful term delivery. A Medline/OVID English language search, covering the period 1982-2012, identified 38 additional cases of CEPs treated with single-dose IM MTX. Of the total 40 cases analyzed, including our 2 cases, 30 (75%) were successfully treated, with complete remission. Of the 27 cases with no embryonic cardiac activity, 25 (93%) were successfully treated with single-dose IM MTX. CONCLUSION: Appropriately selected cases of CEPs can be successfully managed with single-dose IM MTX with very low complication rates and preservation of future fertility potential.

Emotional Impact of Reduced Access to Assisted Reproductive Care.

OBJECTIVE: To evaluate the impact of cessation of fertility services on patients with infertility. STUDY DESIGN: A cross-sectional, anonymous mail survey was conducted in a university hospital setting. A total of 281 female infertility patients treated from 2003-2006 were mailed surveys. The main outcome measures of the study were the Perceived Stress Scale 10 (PSS-10) and the Impact of Events Scale (IES). RESULTS: Of the 281 patients, 175 (62.3%) responded to the questionnaire. Of those, 51 (29.1%) reported being affected by the closure. The majority (58.9%) reported a somewhat or very negative impact on their perceived quality of life. Affected patients were more likely than unaffected patients to have an elevated PSS-10 result (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.04-4.3). No significant difference was seen in IES results, with 90.2% of affected and 81.5% of unaffected patients scoring in the high distress range (OR 2.1, 95% CI 0.77-5.65). Self-reported average stress levels were reduced following news of resumption of services (3.3, scale 1-10) as compared to both prior to (5.1) and during (7.4) the closure. CONCLUSION: When fertility services are discontinued, there may be significant emotional distress among the population affected. Health care providers should be aware of the impact infertility has on stress-coping and quality of life and be prepared to offer psychological services.

Progesterone support for frozen embryo transfer: intramuscular versus vaginal suppository demonstrates no difference in a cohort.

OBJECTIVE: To evaluate pregnancy rates based on the route of progesterone replacement in frozen embryo transfer (FET) cycles. STUDY DESIGN: A randomized controlled trial and retrospective analysis. In the randomized group 76 FET cycles were randomized. In the retrospective group 508 FET cycles were reviewed. Intramuscular (IM) proges-erone in oil 100 mg daily or oral micronized progesterone prior to transfer followed by compounded vaginal proges-erone 200 mg 3 times daily (OV). The main outcome measure was the clinical pregnancy rate (CPR). RESULTS: Baseline characteristics did not vary be-ween groups in either cohort. In the randomized group there were no significant differences in CPR (31.43% vs. 21.05%) or live birth rate (LBR) (31.43% vs. 18.92%) for IM and OV progesterone replacement, respectively. In the retrospective cohort patients there wore also no significant differences in CPR (35.56% vs. 32.35%) or LBR (32.23% vs. 28.51%)f or the IM and OVp rogester-ne replacement groups, respectively. CONCLUSION: This study demonstrates that either OV or IM progesterone is effective for luteal phase support for FETs.

Lower Pregnancy and Live Birth Rates with Vaginal Endometrin Plus Intramuscular Progesterone Every Third Day Versus Intramuscular Progesterone Alone in Programmed Frozen Embryo Transfers: A Retrospective Case-control Study.

This study aimed to determine whether the use of vaginal Endometrin plus intramuscular progesterone on every third day (VIM) in programmed frozen embryo transfer (FET) is associated with lower pregnancy and live birth rates compared to daily intramuscular progesterone (IM). FET data from a single program were collected between November 2018 and December 2021. A total of 903 FETs were analyzed, including 504 FETs in the IM group, and 399 FETs in the VIM group. Inclusion criteria were women undergoing FETs with either 50 mg daily IM progesterone only (control) or 200 mg Endometrin twice daily plus 50 mg IM progesterone on every third day, with the transfer of a single day 5 or 6 frozen embryo. There were no significant differences in patient age at time of FETs, BMI, endometrial thickness, blastocyst quality, or infertility diagnosis between the groups. The VIM had significantly lower positive hCG and clinical pregnancy rates compared to the IM (60.2% vs 72.0% and 40.6% vs 56.7%, respectively, P = 0.0002 and P < 0.0001). The live birth rate was 36.1% in the VIM, compared to 49.4% in the IM (P < 0.0001). These findings also remained significant when excluding FETs with donor egg (35.9% vs 50.1%, P < 0.0001). This study demonstrated that VIM in FET cycles yields significantly lower pregnancy and live birth rates compared to IM along. IM progesterone alone may be preferable to combined Endometrin and IM progesterone in patients undergoing programmed frozen embryo transfers.

Hospitalizations up to 8 years following delivery in assisted reproductive technology-treated and subfertile women.

OBJECTIVE: To investigate hospitalizations up to 8 years after live birth among women who used assisted reproductive technology (ART) or who were subfertile compared with women who conceived naturally. DESIGN: Retrospective cohort. SETTING: Deliveries among privately insured women aged ≥18 years between 2004 and 2017 from Massachusetts state vital records were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System and hospital observational/inpatient stays. PATIENT(S): We compared patients with ART, medically assisted reproduction (MAR), and unassisted subfertile (USF) delivery with those with fertile delivery. INTERVENTION(S): NA. MAIN OUTCOME MEASURE(S): Postdelivery hospitalization information was derived from the International Classification of Diseases codes for discharges and combined by type. The relative risks and 95% confidence intervals (CIs) of hospitalization for up to the first 8 years postdelivery were modeled. RESULT(S): Among 492,515 deliveries, 5.6% used ART, 1.6% used MAR, and 1.8% were USF. Compared with fertile deliveries, deliveries that used ART or MAR or were USF were more likely to have hospital utilization (inpatient or observational stay) for any reason for up to 8 years of follow-up (USF, adjusted relative risk [aRR], 1.18 [95% CI, 1.12-1.25]; MAR, aRR, 1.20 [1.13-1.27]; and ART, aRR, 1.29 [1.25-1.34]). Assisted reproductive technology deliveries had an increased risk of hospitalization for conditions of the cardiovascular system (aRR, 1.31 [95% CI, 1.20-1.41]), overweight/obesity (aRR, 1.30 [1.17-1.44]), diabetes (aRR, 1.25 [1.05-1.49]), reproductive tract (aRR, 1.62 [1.47-1.79]), digestive tract (aRR, 1.39 [1.30-1.49]), thyroid (aRR, 2.02 [1.80-2.26]), respiratory system (aRR, 1.13 [1.03-1.24]), and cancer (aRR, 1.40 [1.18-1.65]) up to 8 years after delivery. Deliveries with MAR and subfertility had similar patterns of hospitalization as ART deliveries. CONCLUSION(S): Women who conceived through fertility treatment or experienced subfertility were at increased risk of subsequent hospitalization resulting from a variety of chronic and acute conditions.