Trace elements and endometriosis: the ENDO study.

There has been limited study of trace elements and endometriosis. Using a matched cohort design, 473 women aged 18-44 years were recruited into an operative cohort, along with 131 similarly aged women recruited into a population cohort. Endometriosis was defined as surgically visualized disease in the operative cohort, and magnetic resonance imaging diagnosed disease in the population cohort. Twenty trace elements in urine and three in blood were quantified using inductively coupled plasma mass spectrometry. Logistic regression estimated the adjusted odds (aOR) of endometriosis diagnosis for each element by cohort. No association was observed between any element and endometriosis in the population cohort. In the operative cohort, blood cadmium was associated with a reduced odds of diagnosis (aOR=0.55; 95% CI: 0.31, 0.98), while urinary chromium and copper reflected an increased odds (aOR=1.97; 95% CI: 1.21, 3.19; aOR=2.66; 95% CI: 1.26, 5.64, respectively). The varied associations underscore the need for continued research.

Is infertility associated with childhood autism?

Concerns persist about a possible link between infertility and risk of autism spectrum disorders (ASD). Interpretation of existing studies is limited by racial/ethnic homogeneity of study populations and other factors. Using a case-control design, we evaluated infertility history and treatment documented in medical records of members of Kaiser Permanente Northern California. Among singletons (349 cases, 1,847 controls), we found no evidence to support an increase in risk of ASD associated with infertility. Among multiple births (21 cases, 54 controls), we found an increased risk associated with infertility history and with infertility evaluations and treatment around the time of index pregnancy conception; however, small sample size and lack of detailed data on treatments preclude firm interpretation of results for multiple births.

Perfluorochemicals and endometriosis: the ENDO study.

BACKGROUND: Environmental chemicals may be associated with endometriosis. No published research has focused on the possible role of perfluorochemicals (PFCs) despite their widespread presence in human tissues. METHODS: We formulated two samples. The first was an operative sample comprising 495 women aged 18-44 years scheduled for laparoscopy/laparotomy at one of 14 participating clinical sites in the Salt Lake City or San Francisco area, 2007-2009. The second was a population-based sample comprising 131 women matched to the operative sample on age and residence within a 50-mile radius of participating clinics. Interviews and anthropometric assessments were conducted at enrollment, along with blood collection for the analysis of nine PFCs, which were quantified using liquid chromatography-tandem mass spectrometry. Endometriosis was defined based on surgical visualization (in the operative sample) or magnetic resonance imaging (in the population sample). Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for each PFC (log-transformed), adjusting for age and body mass index, and then parity. RESULTS: Serum perfluorooctanoic acid (PFOA; OR = 1.89 [95% CI = 1.17-3.06]) and perfluorononanoic acid (2.20 [1.02-4.75]) were associated with endometriosis in the operative sample; findings were moderately attenuated with parity adjustment (1.62 [0.99-2.66] and 1.99 [0.91-4.33], respectively). Perfluorooctane sulfonic acid (1.86 [1.05-3.30]) and PFOA (2.58 [1.18-5.64]) increased the odds for moderate/severe endometriosis, although the odds were similarly attenuated with parity adjustment (OR = 1.50 and 1.86, respectively). CONCLUSIONS: Select PFCs were associated with an endometriosis diagnosis. These associations await corroboration.

Comparing apples and pears: women's perceptions of their body size and shape.

BACKGROUND: Obesity is a growing public health problem among reproductive-aged women, with consequences for chronic disease risk and reproductive and obstetric morbidities. Evidence also suggests that body shape (i.e., regional fat distribution) may be independently associated with risk, yet it is not known if women adequately perceive their shape. This study aimed to assess the validity of self-reported body size and shape figure drawings when compared to anthropometric measures among reproductive-aged women. METHODS: Self-reported body size was ascertained using the Stunkard nine-level figures and self-reported body shape using stylized pear, hourglass, rectangle, and apple figures. Anthropometry was performed by trained researchers. Body size and body mass index (BMI) were compared using Spearman's correlation coefficient. Fat distribution indicators were compared across body shapes for nonobese and obese women using analysis of variance (ANOVA) and Fisher's exact test. Percent agreement and kappa statistics were computed for apple and pear body shapes. RESULTS: The 131 women studied were primarily Caucasian (81%), aged 32 years, with a mean BMI of 27.1 kg/m(2) (range 16.6-52.8 kg/m(2)). The correlation between body size and BMI was 0.85 (p<0.001). Among nonobese women, waist-to-hip ratios (WHR) were 0.75, 0.75, 0.80, and 0.82 for pear, hourglass, rectangle, and apple, respectively (p<0.001). Comparing apples and pears, the percent agreement (kappa) for WHR≥0.80 was 83% (0.55). CONCLUSIONS: Self-reported size and shape were consistent with anthropometric measures commonly used to assess obesity and fat distribution, respectively. Self-reported body shape may be a useful proxy measure in addition to body size in large-scale surveys.

Preterm delivery and low birth weight in singleton pregnancies conceived by women with and without a history of infertility.

OBJECTIVE: To determine predictors of low birth weight (LBW) and preterm delivery (PTD) in singleton pregnancies conceived by women with and without a history of infertility. DESIGN: Retrospective cohort study. SETTING: Eleven infertility clinics in northern California. PATIENT(S): Three groups of women who carried singleton pregnancies to ≥20 weeks' gestation: 542 infertile women who conceived after treatment, 441 infertile women who conceived spontaneously, and 1,008 fertile women for comparison. INTERVENTION(S): Chart review. MAIN OUTCOME MEASURE(S): Association of LBW or PTD with infertility treatment, maternal age, parity, obesity, or development of gestational diabetes. RESULT(S): Infertile women who conceived with treatment were more likely to be obese, develop gestational diabetes, and have ovarian, ovulatory, or male factor infertility than infertile women who conceived spontaneously. Infertile women who conceived after treatment had 1.61 times greater odds of having an LBW infant. Nulliparity was an independent predictor of LBW and PTD in all three groups after controlling for maternal age, history of infertility, infertility treatment, obesity, and gestational diabetes. CONCLUSION(S): Nulliparous women and women with a history of infertility who conceive a singleton after treatment may be at increased odds for having an LBW infant. Infertile women do not appear to be at increased odds for PTD.

Persistent lipophilic environmental chemicals 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]; ß-HCH was the only significant predictor in the population cohort (per 1-SD increase in log-transformed ß-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.

Fecundity and sex ratio of offspring in an infertile cohort.

OBJECTIVE: To determine whether male and female subfecundity is associated with the gender ratio. DESIGN: Retrospective cohort study. SETTING: Reproductive endocrinology clinics in California. PATIENT(S): A cohort of 30,448 women who sought infertility treatment or evaluation in California between 1990 and 1998 was identified. A fertile comparison group was assembled after matching data from vital statistics records. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Multivariate logistic regression was used to determine the odds of a male birth based on fertility status. RESULT(S): We identified 5,293 infertile women and 6,730 fertile matched women in the live-birth and fetal death records. There were 6,178 children born to women evaluated and/or treated for infertility, compared with 9,131 born to fertile women, for a total of 15,309 births. There was no significant difference in the secondary sex ratio between births in the infertile cohort and the fertile cohort or on the basis of male factor infertility versus female factor infertility. After controlling for confounding factors, there was no difference in sex ratio based on the use of advanced reproductive technologies, duration of infertility treatment, or the type of infertility. CONCLUSION(S): This study found no statistical evidence to support an association between infertility and secondary sex ratio.

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 $1,182 for medications only to $24,373 and $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--$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.

Increased risk of high-grade prostate cancer among infertile men.

BACKGROUND: 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. METHODS: A total of 22,562 men who were evaluated for infertility from 1967 to 1998 were identified from 15 California infertility centers and linked to the California Cancer Registry. The incidence of prostate cancer was compared with the incidence in an age-matched and geography-matched sample of men from the general population. The risk of prostate cancer in men with and those without male factor infertility was modeled using a Cox proportional hazards regression model. RESULTS: A total of 168 cases of prostate cancer that developed after infertility were identified. Men evaluated for infertility but not necessarily with male factors were not found to have an increased risk of cancer compared with the general population (standardized incidence ratio [SIR], 0.9; 95% confidence interval [95% CI], 0.8-1.1). This risk was found to be highest for men with male factor infertility who developed high-grade prostate cancer (SIR, 2.0; 95% CI, 1.2-3.0). On multivariate analyses, men with male factor infertility were found to be 2.6 times more likely to be diagnosed with high-grade prostate cancer (hazard ratio, 2.6; 95% CI, 1.4-4.8). CONCLUSIONS: Men with male factor infertility were found to have an increased risk of subsequently developing high-grade prostate cancer. Male infertility may be an early and identifiable risk factor for the development of clinically significant prostate cancer.

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.

Differences in the clinical characteristics of primarily and secondarily infertile men with varicocele.

OBJECTIVE: To compare the clinical characteristics of primarily and secondarily infertile men with varicocele. DESIGN: Cross-sectional analysis. SETTING: Male infertility clinic, tertiary health care center. PATIENT(S): Two hundred ninety-five infertile men with palpable varicoceles. INTERVENTION(S): Clinical evaluation including patient reproductive history (including assessment of primary or secondary infertility), physical examination, hormonal assessment and at least two semen analyses. MAIN OUTCOME MEASURE(S): Differences in the characteristics of men with primary vs. secondary infertility. RESULT(S): Two hundred five subjects were identified with primary infertility and 90 with secondary infertility. Secondarily infertile men were older (39.6 years vs. 35.0 years), with older partners (35.4 years vs. 33.2 years), but had higher sperm densities (51.3 vs. 36.0 million/mL) and a greater percentage of morphologically normal sperm (30.6% vs. 24.1%). A lower proportion of secondarily infertile men had total motile sperm count (TMC) <20 million compared with primarily infertile men (31.1% vs. 46.5%). Groups did not differ regarding infertility duration, tobacco or alcohol use, varicocele grade or laterality, testis volumes, or hormonal parameters. In multivariate modeling, secondary infertility (vs. primary) was an independent predictor of TMC >20 million (odds ratio 1.9). CONCLUSION(S): Men with secondary infertility are older and have older partners than primarily infertile men, yet they have significantly better sperm concentrations. Infertility in this group may be influenced by maternal reproductive potential.

Bilateral but not unilateral testicular hypotrophy predicts for severe impairment of semen quality in men with varicocele undergoing infertility evaluation.

OBJECTIVES: Varicocele is a common cause of infertility, and varicocele-associated testicular hypotrophy has been described as a potential cause of decreased semen quality. We investigated the relationship between testicular hypotrophy and poor semen quality in infertile men with varicoceles. We hypothesized that bilateral hypotrophy is required before the semen quality is severely impaired. METHODS: We retrospectively identified consecutive patients with palpable varicoceles undergoing an infertility evaluation at a single academic center. Each patient was evaluated by the same clinician with history and physical examination. Testicular hypotrophy was defined as a size discrepancy of greater than 3 mL or an absolute size of less than 14 mL. Multivariate logistic regression analysis was used to determine the clinical predictors of total motile sperm count (TMC) of less than 20 million. RESULTS: A total of 245 men with complete data were identified, and 103 men with a TMC of less than 20 million sperm (mean age 36.2 +/- 6.6 years) were compared with 142 men with normal TMCs (mean age 37.1 +/- 6.5 years). On multivariate analysis, men with bilateral hypotrophy were nearly nine times more likely to have a TMC of less than 20 million sperm than were men without hypotrophy (odds ratio 8.8, 95% confidence interval 2.4 to 32.1), and six times more likely than those with unilateral hypotrophy (odds ratio 6.0, 95% confidence interval 1.4 to 26.3). Unilateral hypotrophy alone did not predict for a low TMC. CONCLUSIONS: Among men with varicoceles undergoing infertility evaluation, those with bilateral hypotrophy are at the greatest risk of impaired semen quality.

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

PURPOSE: There are marked racial differences in the incidence of testicular germ cell tumors among United States men, with whites having 5 times the incidence of blacks and 3 times that of Asians. Testicular germ cell tumors in boys are rare, and limited racial classification by cancer registries has made attempts to discern racial patterns difficult. We hypothesize that recent diversification of race data by cancer registries may allow for more accurate racial classification, and that there are racial differences in the incidence of testicular germ cell tumors in prepubertal boys. MATERIALS AND METHODS: We identified all cases of histologically confirmed testicular germ cell cancer in boys 0 to 14 years old between 1992 and 2004 through the Surveillance, Epidemiology and End Results Program. We performed subgroup analysis in boys 0 to 9 years old. Race was categorized as white, black, American Indian/Alaska Native or Asian/Pacific Islander. Variables analyzed included age, tumor histology and year of diagnosis. RESULTS: A total of 695 cases of testicular germ cell tumors were diagnosed among boys of all races, with an overall incidence of 6.3 per 1 million person-years. Testicular germ cell tumors were 1.4-fold more likely to develop in Asian/Pacific Islanders compared to whites (RR 1.4, 95% CI 1.1 to 1.8). Increased rates among Asian/Pacific Islanders were constant across all age strata, in cases of yolk sac tumor/embryonal, teratoma and seminoma, and were maintained from 1992 to 2004. CONCLUSIONS: Asian/Pacific Islander boys are more likely to have testicular germ cell tumors compared to whites. Similar to adults, race appears to have a significant role in the incidence of testicular germ cell tumors among prepubertal boys.

The relative accuracy of a questionnaire compared with pedigree analysis in genetic risk assessment for infertility.

PURPOSE: For infertile couples family history assessment can add valuable information about genetic infertility and possible risks for offspring. We created a genetic questionnaire for eliciting family history and asked whether it could capture information similar to a pedigree. MATERIALS AND METHODS: Infertile male patients completed a genetic questionnaire and had a pedigree obtained by a genetic counselor. We assessed the accuracy of the questionnaire to elicit family history information compared to the gold standard pedigree. RESULTS: Of 93 patients 76 (82%) patients indicated relevant genetic information. A comparison of the 2 methods revealed that 61 (80%) patients failed to report key genetic information on the questionnaire that was ascertained by the pedigree. Assessment of 5 relevant family history elements revealed that the questionnaire missed 75% or more of stillbirths, birth defects, developmental delay/learning disabilities/mental retardation, recurrent miscarriages and congenital heart defects. The positive predictive value and the negative predictive value of the questionnaire ranged from 67% to 100% and 74% to 87%, respectively. The sensitivity and specificity of the questionnaire ranged from 12% to 30% and 98% to 100%, respectively. CONCLUSIONS: A comprehensive family history questionnaire is not as reliable for capturing relevant, genetic information as a pedigree. The optimal method will become more important as our knowledge of genetic infertility and its implications expands.

Prepubertal orchiopexy for cryptorchidism may be associated with lower risk of testicular cancer.

PURPOSE: Current indications for orchiopexy are to decrease the risk of infertility and to facilitate testicular self-examination. Although the increased risk of germ cell cancer in cryptorchid testes is undisputed, it is unclear whether orchiopexy affects the natural history of testis cancer development. We hypothesize that early orchiopexy is protective against subsequent development of testicular germ cell cancer. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of the literature. Studies pertaining to cryptorchidism and testicular cancer risk were retrieved by searching MEDLINE, BIOSIS and the Cochrane Library, using cryptorchidism as a keyword, combined with treatment, orchiopexy, testis and cancer. For data extraction exposure was dichotomized to orchiopexy before or after age 10 to 11 years, while outcome was defined as the development of testicular germ cell cancer. Summary risk measures were calculated using the random effects model. RESULTS: Four studies met our criteria. Review of all studies revealed an increased risk of testicular cancer if orchiopexy was delayed until after age 10 to 11 years or was never performed. Odds ratios ranged from 2.9 to 32.0. Meta-analysis showed that testicular cancer was nearly 6 times more likely (OR 5.8 [1.8, 19.3]) to develop in men in whom orchiopexy was delayed or was not performed, compared to those in whom it was performed early. CONCLUSIONS: Prepubertal orchiopexy may decrease the risk of testicular cancer. Thus, early surgical intervention is indicated in children with cryptorchidism. These findings suggest that the testicular environment, as well as underlying genetics, may have a role in testicular carcinogenesis.

Potential association between infertility and spinal neural tube defects in offspring.

BACKGROUND: We examined the possible association between infertility and spinal neural tube defects (NTDs). METHODS: This is a nested case-control study within the Kaiser Permanente Medical Care Program (KPMCP) in Northern California. Among a birth cohort of 110,624 singleton infants > or = 36 weeks gestation, 1994-1997, we electronically identified cases of spinal NTDs and confirmed the diagnosis by chart review. Controls (n = 1,608) were randomly selected from the birth population. History of infertility was defined as: (1) physician diagnosis of infertility; (2) prescription for an infertility medication noted in the KPMCP pharmacy; and/or (3) evaluation at 1 of 15 infertility clinics in Northern California. RESULTS: Eighteen infants diagnosed with spinal NTDs (prevalence 1.6/10,000) included 13 with spina bifida cystica and 5 with spina bifida occulta. Case mothers were more likely to have a history of infertility (4/18 vs. 96/1,608, OR 4.3, 95% CI 1.01-14.0), and to have been prescribed clomiphene citrate within the window spanning 60 days before to 15 days after conception (3/18 vs. 32/1,608, OR 11.7, 95% CI 2.0-44.8). CONCLUSION: This exploratory study suggests that infertility may be associated with an increased risk of spinal NTDs among liveborn, term infants.

Gonadotropin stimulation demonstrates a ceiling effect on in vitro fertilization outcomes.

OBJECTIVE: To determine the effect of number of oocytes retrieved and number of 2PN embryos developed on in vitro fertilization (IVF) outcomes. DESIGN: Retrospective data analysis. SETTING: University practice. PATIENT(S): Reproductive-aged women (n = 467). INTERVENTION(S): First fresh nondonor cycle of IVF. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate RESULT(S): Clinical pregnancy rates increase until age 30 (odds ratio (OR) 1.72 per year (95% confidence interval 1.19-2.49)) before demonstrating a linear decline. In subjects < 37 years old, maximal clinical pregnancy rates are seen when 20 oocytes were retrieved (OR 1.03 (0.96-1.11)), five 2-pronuclei (2PN) embryos developed (OR 1.91 (1.29-2.87)), and no more than two embryos transferred (OR 0.72 (0.56-0.92) for each additional embryo transferred > 2). In subjects > or = 37 years old, maximum clinical pregnancy rates were achieved in subjects who had ten oocytes retrieved (OR 1.09 (1.01-1.18)), 20 2PN embryos developed (OR 1.29 (1.03-1.62)), and no more than two embryos transferred (OR 0.72 (0.56-0.92) for each additional embryo transferred > 2). CONCLUSION(S): The odds of achieving a successful clinical pregnancy with IVF are greatest with retrieval of approximately 20 oocytes, transfer of no more than 2 embryos, and the development of about five 2PN embryos in women < 37 years old and ten 2PN embryos in women > or = 37 years old.

Maternal progestin intake and risk of hypospadias.

BACKGROUND: Previous studies have suggested that maternal intake of progestins during early pregnancy may be associated with an increased risk of hypospadias. Progesterone and its derivatives are commonly prescribed during early pregnancy, for example, in cases of luteal phase dysfunction and in conjunction with ovulation stimulation drugs. OBJECTIVE: To examine whether risk of hypospadias was associated with periconceptional progestin intake. DESIGN AND SETTING: The National Birth Defects Prevention Study, a population-based, multistate, case-control study including deliveries that had estimated due dates from October, 1997 to December, 2000. PARTICIPANTS: Participation in the study was 71% among case mothers and 68% among control mothers. This analysis included 502 subjects diagnosed with second- or third-degree hypospadias (ie, the urethra opened at the penile shaft, scrotum, or perineum) and 1286 male, live-born, nonmalformed control subjects. RESULTS: Forty-two case mothers (8.4%) and 31 control mothers (2.4%) reported any pregnancy-related progestin intake from 4 weeks before through 14 weeks after conception, resulting in an odds ratio of 3.7 (95% confidence interval [CI], 2.3-6.0). Analyses stratified by several potential covariates also suggested elevated risks. For example, among the 10 cases and 13 controls who did not report any fertility-related procedures or treatments other than progestins, the odds ratio was 2.2 (95% CI, 1.0-5.0). Progestin intake for the purpose of contraception was not associated with increased risk. CONCLUSION: This study found that pregnancy-related intake of progestins was associated with increased hypospadias risk.

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," "pre-term 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.

Neonatal outcomes in immediate versus delayed conceptions after spontaneous abortion: a retrospective case series.

OBJECTIVE: This study was undertaken to determine differences in neonatal outcomes between successful pregnancies conceived immediately after a spontaneous abortion (SAB) and successful pregnancies conceived after two menstrual cycles or at least 100 days from the spontaneous abortion. STUDY DESIGN: This study was a retrospective case series. Deliveries were identified from the University of California-San Francisco Perinatal Database among patients with a history of one SAB. Medical records of 268 patients were reviewed. Sixty-four patients fulfilled study criteria, with 19 in the immediate conception group and 45 in the delayed conception group. Categorical variables were analyzed using chi(2) tests and Fisher exact tests for variables with expected values of <5, whereas continuous variables were analyzed using Student t tests. RESULTS: Neonatal outcomes for the 2 groups were similar, although neonates in the delayed conception group were more likely to have at least one of the following: low birth weight, an Apgar score <7 at 5 minutes, or admission to the neonatal intensive care unit. CONCLUSION: In this small retrospective case series, there was no evidence of adverse neonatal outcomes associated with conception immediately after a SAB.