Mary S. Croughan

Perinatal outcomes in singletons following in vitro fertilization: A meta-analysis

OBJECTIVE: To estimate whether singleton pregnancies following in vitro fertilization (IVF) are at higher risk of perinatal mortality, preterm delivery, small for gestational age, and low or very low birth weight compared with spontaneous conceptions in studies that adjusted for age and parity. DATA SOURCES: We searched MEDLINE, BIOSIS, Doctoral Dissertations On-Line, bibliographies, and conference proceedings for studies from 1978–2002 using the terms “in vitro fertilization,” “female infertility therapy,” and “reproductive techniques” combined with “fetal death,” “mortality,” “fetal growth restriction,” “small for gestational age,” “birth weight,” “premature labor,” “preterm delivery,” “infant,” “obstetric,” “perinatal,” and “neonatal.” METHODS OF STUDY SELECTION: Inclusion criteria were singleton pregnancies following IVF compared with spontaneous conceptions, control for maternal age and parity; 1 of the above outcomes; and risk ratios or data to determine them. Study selection and data abstraction were performed in duplicate after removing identifying information. TABULATION, INTEGRATION, AND RESULTS: Fifteen studies comprising 12,283 IVF and 1.9 million spontaneously conceived singletons were identified. Random-effects meta-analysis was performed. Compared with spontaneous conceptions, IVF singleton pregnancies were associated with significantly higher odds of each of the perinatal outcomes examined: perinatal mortality (odds ratio [OR] 2.2; 95% confidence interval [CI] 1.6, 3.0), preterm delivery (OR 2.0; 95% CI 1.7, 2.2), low birth weight (OR 1.8; 95% CI 1.4, 2.2), very low birth weight (OR 2.7; 95% CI 2.3, 3.1), and small for gestational age (OR 1.6; 95% CI 1.3, 2.0). Statistical heterogeneity was noted only for preterm delivery and low birth weight. Sensitivity analyses revealed no significant changes in results. Early preterm delivery, spontaneous preterm delivery, placenta previa, gestational diabetes, preeclampsia, and neonatal intensive care admission were also significantly more prevalent in the IVF group. CONCLUSION: In vitro fertilization patients should be advised of the increased risk for adverse perinatal outcomes. Obstetricians should not only manage these pregnancies as high risk but also avoid iatrogenic harm caused by elective preterm labor induction or cesarean.

Increased Risk of Testicular Germ Cell Cancer Among Infertile Men

BACKGROUND The risk of testicular cancer is thought to be higher among men seeking infertility treatment compared with the general population. Confirmation of this risk in a large US cohort of at-risk patients is lacking. This study explored the association between male infertility and subsequent development of testicular cancer in a US-based cohort. METHODS A total of 51 461 couples evaluated for infertility from 1967 to 1998 were recruited from 15 California infertility centers. We linked data on 22 562 identified male partners to the California Cancer Registry. The incidence of testicular cancer in this cohort was compared with the incidence in an age-matched sample of men from the general population using the Surveillance Epidemiology and End Results program. We analyzed the risk for testicular cancer in men with and without male factor infertility using a Cox proportional hazards regression model. RESULTS Thirty-four post-infertility-diagnosis cases of histologically confirmed testicular cancer were identified. Men seeking infertility treatment had an increased risk of subsequently developing testicular cancer (standardized incidence ratio, 1.3; 95% confidence interval, 0.9-1.9), with a markedly higher risk among those with known male factor infertility (2.8; 1.5-4.8). In multivariable analysis, men with male factor infertility were nearly 3 times more likely to develop testicular cancer compared with those without (hazard ratio, 2.8; 95% confidence interval, 1.3-6.0). CONCLUSION Men with male factor infertility have an increased risk of subsequently developing testicular cancer, suggesting the existence of common etiologic factors for infertility and testicular cancer.

Increased Risk of High-Grade Prostate Cancer Among Infertile Men

It has been reported that fatherhood status may be a risk factor for prostate cancer. In the current study, the authors examined the subsequent occurrence of prostate cancer in a cohort of men evaluated for infertility to determine whether male infertility is a risk factor for prostate cancer.

Costs of infertility treatment: results from an 18-month prospective cohort study

OBJECTIVE To examine resource use (costs) by women presenting for infertility evaluation and treatment over 18 months, regardless of treatment pursued. DESIGN Prospective cohort study in which women were followed for 18 months. SETTING Eight infertility practices. PATIENT(S) Three hundred ninety-eight women recruited from infertility practices. INTERVENTION(S) Women completed interviews and questionnaires at baseline and after 4, 10, and 18 months of follow-up. Medical records were abstracted after 18 months to obtain details of services used. MAIN OUTCOME MEASURE(S) Per-person and per-successful-outcome costs. RESULT(S) Treatment groups were defined as highest intensity treatment use. Twenty percent of women did not pursue cycle-based treatment; approximately half pursued IVF. Median per-person costs ranged from

Bisphenol A and phthalates and endometriosis: the Endometriosis: Natural History, Diagnosis and Outcomes Study

1,182 for medications only to

Persistent Lipophilic Environmental Chemicals and Endometriosis: The ENDO Study

24,373 and

Wet heat exposure: a potentially reversible cause of low semen quality in infertile men

38,015 for IVF and IVF-donor egg groups, respectively. Estimates of costs of successful outcomes (delivery or ongoing pregnancy by 18 months) were higher--

Perfluorochemicals and endometriosis: the ENDO study.

61,377 for IVF, for example--reflecting treatment success rates. Within the time frame of the study, costs were not significantly different for women whose outcomes were successful and women whose outcomes were not. CONCLUSION(S) Although individual patient costs vary, these cost estimates developed from actual patient treatment experiences may provide patients with realistic estimates to consider when initiating infertility treatment.

Racial differences among boys with testicular germ cell tumors in the United States.

OBJECTIVE To explore the relation between bisphenol A and 14 phthalate metabolites and endometriosis. DESIGN Matched cohort design. SETTING Fourteen clinical centers. PATIENT(S) The operative cohort comprised 495 women undergoing laparoscopy/laparotomy, whereas the population cohort comprised 131 women matched on age and residence. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Surgically visualized or pelvic magnetic resonance imaging diagnosed endometriosis in the two cohorts, respectively. RESULT(S) Odds ratios (OR) and 95% confidence intervals (CIs) were estimated using logistic regression adjusting for age, body mass index, and creatinine. In the population cohort, six phthalate metabolites-mono-n-butyl phthalate, mono-[(2-carboxymethyl) hexyl] phthalate, mono (2-ethyl-5-carboxyphentyl) phthalate, mono (2-ethylhexyl) phthalate, mono (2-ethyl-5-hydroxyhexyl) phthalate, and mono (2-ethyl-5-oxohexyl) phthalate-were significantly associated with an approximately twofold increase in the odds of an endometriosis diagnosis. Two phthalates were associated with endometriosis in the operative cohort when restricting to visualized and histologic endometriosis (monooctyl phthalate; OR 1.38; 95% CI 1.10-1.72) or when restricting comparison women to those with a postoperative diagnosis of a normal pelvis [mono (2-ethylhexyl) phthalate; OR 1.35; 95% CI 1.03-1.78]. CONCLUSION(S) Select phthalates were associated with higher odds of an endometriosis diagnosis for women with magnetic resonance imaging-diagnosed endometriosis. The lack of consistency of findings across cohorts underscores the impact of methodology on findings.

Trace elements and endometriosis: The ENDO Study

Background: An equivocal literature exists regarding the relation between persistent organochlorine pollutants (POPs) and endometriosis in women, with differences attributed to methodologies. Objectives: We assessed the association between POPs and the odds of an endometriosis diagnosis and the consistency of findings by biological medium and study cohort. Methods: Using a matched cohort design, we assembled an operative cohort of women 18–44 years of age undergoing laparoscopy or laparotomy at 14 participating clinical centers from 2007 to 2009 and a population-based cohort matched on age and residence within a 50-mile catchment area of the clinical centers. Endometriosis was defined as visualized disease in the operative cohort and as diagnosed by magnetic resonance imaging in the population cohort. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for each POP in relation to an endometriosis diagnosis, with separate models run for each medium (omental fat in the operative cohort, serum in both cohorts) and cohort. Adjusted models included age, body mass index, breast-feeding conditional on parity, cotinine, and lipids. Results: Concentrations were higher in omental fat than in serum for all POPs. In the operative cohort, γ-hexachlorocyclohexane (γ-HCH) was the only POP with a significant positive association with endometriosis [per 1-SD increase in log-transformed γ-HCH: adjusted OR (AOR) = 1.27; 95% CI: 1.01, 1.59]; β-HCH was the only significant predictor in the population cohort (per 1-SD increase in log-transformed β-HCH: AOR = 1.72; 95% CI: 1.09, 2.72). Conclusions: Using a matched cohort design, we found that cohort-specific and biological-medium–specific POPs were associated with endometriosis, underscoring the importance of methodological considerations when interpreting findings.