Live birth rates and birth outcomes by diagnosis using linked cycles from the SART CORS database.

PURPOSE: This study uses linked cycles of assisted reproductive technology (ART) to examine cumulative live birth rates, birthweight, and length of gestation by diagnostic category. METHODS: We studied 145,660 women with 235,985 ART cycles reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System during 2004-2010. ART cycles were linked to individual women by name, date of birth, social security number, partner's name, and sequence of ART treatments. The study population included the first four autologous oocyte cycles for women with a single diagnosis of male factor, endometriosis, ovulation disorders, diminished ovarian reserve, or unexplained infertility. Live birth rates were calculated per cycle, per cycle number (1-4), and cumulatively. Birthweight and length of gestation were calculated for singleton births. RESULTS: Within each diagnosis, live birth rates were highest in the first cycle and declined with successive cycles. Women with diminished ovarian reserve had the lowest live birth rate (cumulative rate of 28.3 %); the live birth rate for the other diagnoses were very similar (cumulative rates from 62.1 % to 65.7 %). Singleton birthweights and lengths of gestation did not differ substantially across diagnoses, ranging from 3,112 to 3,286 g and 265 to 270 days, respectively. These outcomes were comparable with national averages for singleton births in the United States (3,296 g and 271 days). CONCLUSION: Women with the diagnosis of diminished ovarian reserve had substantially lower live birth rates. However, singleton birthweights and lengths of gestation outcomes were similar across all other diagnoses.

Is the fertile window extended in women with polycystic ovary syndrome? Utilizing the Society for Assisted Reproductive Technology registry to assess the impact of reproductive aging on live-birth rate.

OBJECTIVE: To assess whether women with polycystic ovary syndrome (PCOS) follow the same age-related decline in IVF outcomes as women with tubal factor infertility over the reproductive life span. PCOS is characterized by increased ovarian reserve as assessed by antral follicle counts and anti-Müllerian hormone levels. It is unclear whether these surrogate markers of ovarian reserve reflect a true lengthening of the reproductive window. DESIGN: Retrospective cohort. SETTING: Not applicable. PATIENT(S): Women with PCOS and tubal factor infertility (42,286 cycles). INTERVENTION(S): IVF. MAIN OUTCOME MEASURE(S): Pregnancy and live-birth rates. RESULT(S): The mean number of oocytes retrieved was higher in women with PCOS compared with in women with tubal factor (16.4 vs. 12.8; odds ratio [OR], 1.27; 95% confidence interval [CI], 1.25-1.29). The clinical pregnancy (42.5% vs. 35.8%; OR, 1.32; 95% CI, 1.27-1.38) and live-birth rates were also increased in women with PCOS (34.8% vs. 29.1%; OR, 1.30; 95% CI, 1.24-1.35). A similar rate of decline in clinical pregnancy and live-birth rates was noted in both groups (20-44 years). The implantation, clinical pregnancy, miscarriage, and live-birth rates were not significantly different for each year after age 40 in the two groups. CONCLUSION(S): Despite a higher oocyte yield in all age groups, women with PCOS over age 40 had similar clinical pregnancy and live-birth rates compared with women with tubal factor infertility. These findings suggest that the reproductive window may not be extended in PCOS and that patients with infertility should be treated in a timely manner despite indicators of high ovarian reserve.

Extended embryo culture and an increased risk of preterm delivery.

OBJECTIVE: To estimate whether extended embryo culture is associated with preterm delivery, very preterm delivery, low birth weight, or a combination of these in neonates conceived through in vitro fertilization (IVF). METHODS: U.S. IVF live births were identified using the Society of Assisted Reproductive Technologies database (2004-2006). Associations were assessed in neonates born after extended embryo culture (day 5 to 6) as compared with cleavage-stage transfer (day 3). Analyses were stratified by singleton and twin birth. Subanalyses in neonates born to oocyte donation recipients and primiparous patients were performed. RESULTS: A total of 69,039 live births were identified; 46,288 neonates were born after cleavage-stage embryo transfer and 22,751 neonates after blastocyst transfer. Singleton IVF births conceived after blastocyst transfer, as compared with cleavage-stage transfer, were at an increased risk for preterm delivery (18.6% compared with 14.4%, respectively; adjusted odds ratio [OR] 1.39, P<.001) and very preterm delivery (2.8% compared with 2.2%, respectively; adjusted OR 1.35, P<.001), but not low birth weight (10.3% compared with 9.1%, respectively; adjusted OR 1.10, P=.06). Findings remained robust in subanalyses. In twin births, adverse outcome was more prevalent in both groups and an association of blastocyst transfer was noted for preterm delivery (67.3% compared with 60.5%; adjusted OR 1.81, P<.001) very preterm delivery (adjusted OR 14.0% compared with 12.0%; adjusted OR 1.75, P<.001), and low birth weight (71.1% compared with 68.6%, adjusted OR 1.19, P<.001). CONCLUSION: Extended culture of embryos from cleavage stage to blastocyst stage increases the risk of preterm delivery. Unless blastocyst transfer results in a reduction in multiple births, it may be contributing to the perinatal morbidity associated with IVF-assisted conception.

In vitro fertilization and adverse childhood outcomes: what we know, where we are going, and how we will get there. A glimpse into what lies behind and beckons ahead.

The majority of perinatal morbidity after in vitro fertilization (IVF) is due to multiple pregnancy; however, even singleton infants are at an increased risk for adverse outcomes. We have summarized data that evaluates adverse outcomes in IVF infants and recent attempts to delineate the underlying causes of this risk. We submit that practitioners of reproductive medicine should remain at the forefront of this investigation.

Ovarian stimulation and low birth weight in newborns conceived through in vitro fertilization.

OBJECTIVE: Singleton neonates born after in vitro fertilization (IVF) are at increased risk for low birth weight, preterm delivery, or both. We sought to assess whether the alteration of the peri-implantation maternal environment resulting from ovarian stimulation may contribute to increased risk of low birth weight in IVF births. METHODS: The Society for Assisted Reproductive Technologies database was used to identify IVF-conceived neonates born in the United States between 2004 and 2006. Associations were assessed in neonates born after fresh compared with frozen and thawed embryo transfer in women of similar ovarian responsiveness, in paired analysis of neonates born to the same woman after both types of embryo transfer, and in neonates born after oocyte donation. RESULTS: Of 56,792 neonates identified, 38,626 and 18,166 were conceived after transfer of fresh and frozen embryos, respectively. In singletons, there was no difference in preterm delivery. However, the odds of overall low birth weight (10% compared with 7.2%; adjusted odds ratio [OR] 1.35; 95% confidence interval [CI] 1.20-1.51), low birth weight at term (2.5% compared with 1.2%, adjusted OR 1.73, 95% CI 1.31-2.29), and preterm low birth weight (34.1% compared with 23.8%, adjusted OR 1.49, 95% CI 1.24-1.78) were all significantly higher after fresh embryo transfer. In singletons, after either fresh or frozen embryo transfer in the same patient, this association was even stronger (low birth weight: 11.5% compared with 5.6%, adjusted OR 4.66, 95% CI 1.18-18.38). In oocyte donor recipients who do not undergo any ovarian hormonal stimulation for either a fresh or a frozen embryo transfer, no difference in low birth weight was demonstrated (11.5% compared with 11.3% adjusted OR 0.99, 95% CI 0.82-1.18). CONCLUSION: The ovarian stimulation-induced maternal environment appears to represent an independent mediator contributing to the risk of low birth weight, but not preterm delivery, in neonates conceived after IVF. LEVEL OF EVIDENCE: II.

The association of in vitro fertilization and perinatal morbidity.

In recent years, there has been increasing concern regarding the safety of in vitro fertilization (IVF) because of the potential health impact on these infants. Multiple pregnancy contributes the vast majority of morbidity associated with IVF and, initially, many thought that adverse outcomes after IVF were solely attributable to the high incidence of twin pregnancies. More recently, multiple studies have suggested that IVF singleton pregnancies may be at increased risk for preterm birth, low birth weight, congenital anomalies, perinatal mortality, and several other pregnancy-related complications compared with unassisted singleton pregnancies. We have focused this review on the increased risk of adverse outcomes in IVF singleton conceptions compared with that of unassisted conceptions. The available evidence evaluating the association between IVF and low birth weight, preterm delivery, placental abruption, preeclampsia, congenital anomalies, and perinatal mortality in singleton pregnancies is summarized. In addition, data reporting an increased risk of congenital and chromosomal anomalies after IVF are presented.

Symptomatic fibroids in two patients on hormone replacement therapy with primary ovarian failure secondary to prepubertal gonadotoxic cancer treatment.

BACKGROUND: We report two childhood cancer patients with primary ovarian failure who underwent exogenous hormone-induced puberty and had symptomatic fibroids while on hormone replacement therapy (HRT). CASES: A 26-year-old woman with a history of myelodysplastic syndrome complained of irregular, heavy menstrual bleeding and painful menses; physical examination revealed a 5 cm x 3.5 cm prolapsing fibroid. A 23-year-old woman with a history of acute lymphocytic leukemia complained of irregular and heavy menstrual bleeding; physical examination revealed a 5.5 cm prolapsing fibroid. CONCLUSIONS: Patients with primary ovarian failure who are on HRT are capable of developing symptomatic fibroids despite lack of endogenously induced puberty. Diagnosis may be delayed if symptomatic uterine fibroids are not included in the differential diagnosis of abnormal uterine bleeding and pain.