The Role of Multiple Birth and Birth Complications in the Association Between Assisted Reproductive Technology Conception and Autism Diagnosis.

In recent decades, the use of assisted reproductive technology (ART) has increased rapidly. To assess the relationship between ART and autism diagnosis, we linked California birth records from 2000 through 2016 with contemporaneous records from the National ART Surveillance System (NASS) and autism caseload records from California's Department of Developmental Services from 2000 through November 2019. All 95,149 birth records that were successfully linked to a NASS record, indicating an ART birth, were matched 1:1 using propensity scores to non-ART births. We calculated the hazard risk ratio (HRR) for autism diagnosis and the proportions of the relationship between ART conception and autism diagnosis mediated by multiple birth pregnancy and related birth complications. The HRR for autism diagnosis following ART compared with non-ART conception is 1.26 (95% CI, 1.17-1.35). Multiple birth, preterm birth, and Cesarean delivery jointly mediate 77.9% of the relationship between ART conception and autism diagnosis. Thus, increased use of single embryo transfer in the United States to reduce multiple births and related birth complications may be a strategy to address the risk of autism diagnosis among ART-conceived children.

Predicted probabilities of live birth following assisted reproductive technology using United States national surveillance data from 2016 to 2018.

BACKGROUND: As the use of in vitro fertilization continues to increase in the United States, up-to-date models that estimate cumulative live birth rates after multiple oocyte retrievals and embryo transfers (fresh and frozen) are valuable for patients and clinicians weighing treatment options. OBJECTIVE: This study aimed to develop models that generate predicted probabilities of live birth in individuals considering in vitro fertilization based on demographic and reproductive characteristics. STUDY DESIGN: Our population-based cohort study used data from the National Assisted Reproductive Technology Surveillance System 2016 to 2018, including 196,916 women who underwent 207,766 autologous embryo transfer cycles and 25,831 women who underwent 36,909 donor oocyte transfer cycles. We used data on autologous in vitro fertilization cycles to develop models that estimate a patient's cumulative live birth rate after all embryo transfers (fresh and frozen) within 12 months after 1, 2, and 3 oocyte retrievals in new and returning patients. Among patients using donor oocytes, we estimated the cumulative live birth rate after their first, second, and third embryo transfers. Multinomial logistic regression models adjusted for age, prepregnancy body mass index (imputed for 18% of missing values), parity, gravidity, and infertility diagnoses were used to estimate the cumulative live birth rate. RESULTS: Among new and returning patients undergoing autologous in vitro fertilization, female age had the strongest association with cumulative live birth rate. Other factors associated with higher cumulative live birth rates were lower body mass index and parity or gravidity ≥1, although results were inconsistent. Infertility diagnoses of diminished ovarian reserve, uterine factor, and other reasons were associated with a lower cumulative live birth rate, whereas male factor, tubal factor, ovulatory disorders, and unexplained infertility were associated with a higher cumulative live birth rate. Based on our models, a new patient who is 35 years old, with a body mass index of 25 kg/m2, no previous pregnancy, and unexplained infertility diagnoses, has a 48%, 69%, and 80% cumulative live birth rate after the first, second, and third oocyte retrieval, respectively. Cumulative live birth rates are 29%, 48%, and 62%, respectively, if the patient had diminished ovarian reserve, and 25%, 41%, and 52%, respectively, if the patient was 40 years old (with unexplained infertility). Very few recipient characteristics were associated with cumulative live birth rate in donor oocyte patients. CONCLUSION: Our models provided estimates of cumulative live birth rate based on demographic and reproductive characteristics to help inform patients and providers of a woman's probability of success after in vitro fertilization.

Association of state insurance coverage mandates with assisted reproductive technology care discontinuation.

BACKGROUND: Insurance coverage for fertility services may reduce the financial burden of high-cost fertility care such as assisted reproductive technology and improve its utilization. Patients who exit care after failing to reach their reproductive goals report higher rates of mental health problems and a lower sense of well-being. It is important to understand the relationship between state-mandated insurance coverage for fertility services and assisted reproductive technology care discontinuation. OBJECTIVE: This study aimed to assess whether state-mandated insurance coverage for fertility services is associated with lower rates of care discontinuation after an initial assisted reproductive technology cycle that did not result in a live birth. STUDY DESIGN: This is a retrospective, population-based cohort study using data from United States fertility clinics reporting to the National Assisted Reproductive Technology Surveillance System during 2016 and 2018. Patients who began their first autologous assisted reproductive technology cycle during 2016 and 2017 and did not have a live birth were included. We describe the rate of assisted reproductive technology care discontinuation (no additional cycle within 12 months of the previous cycle's date of failure). Multivariable analyses were conducted to evaluate factors independently associated with care discontinuation, including the scope of fertility services included in state coverage mandate at assisted reproductive technology cycle initiation that were as follows: comprehensive (≥3 assisted reproductive technology cycles), limited (1, 2, or an unspecified number of assisted reproductive technology cycles), mandate not including assisted reproductive technology, and no mandate. RESULTS: Among 91,324 patients who underwent their first autologous assisted reproductive technology cycle that did not result in live birth, 24,072 (26.4%) discontinued care. Compared with patients who lived in states with mandates for comprehensive assisted reproductive technology coverage, those in states with mandates for fertility services coverage that did not include assisted reproductive technology or states with no mandate were 46% (adjusted relative risk, 1.46; 95% confidence interval, 1.31-1.63) and 26% (adjusted relative risk, 1.26; 95% confidence interval, 1.15-1.39) more likely to discontinue care, respectively, after controlling for patient and cycle characteristics. Increasing patient age, distance from clinic ≥50 miles, previous live birth, fewer oocytes retrieved, and not having embryos cryopreserved were also associated with higher rates of discontinuation. Non-Hispanic Black, non-Hispanic Asian, and Hispanic patients had higher rates of care discontinuation than non-Hispanic White patients regardless of the existence or scope of state-mandated assisted reproductive technology coverage. CONCLUSION: Comprehensive state-mandated insurance coverage for assisted reproductive technology is associated with lower rates of assisted reproductive technology care discontinuation.

Assisted Reproductive Technology and Perinatal Mortality: Selected States (2006-2011).

OBJECTIVE: This study aimed to compare trends and characteristics of assisted reproductive technology (ART) and non-ART perinatal deaths and to evaluate the association of perinatal mortality and method of conception (ART vs. non-ART) among ART and non-ART deliveries in Florida, Massachusetts, and Michigan from 2006 to 2011. STUDY DESIGN: Retrospective cohort study using linked ART surveillance and vital records data from Florida, Massachusetts, and Michigan. RESULTS: During 2006 to 2011, a total of 570 ART-conceived perinatal deaths and 25,158 non-ART conceived perinatal deaths were identified from the participating states. Overall, ART perinatal mortality rates were lower than non-ART perinatal mortality rates for both singletons (7.0/1,000 births vs. 10.2/1,000 births) and multiples (22.8/1,000 births vs. 41.2/1,000 births). At <28 weeks of gestation, the risk of perinatal death among ART singletons was significantly lower than non-ART singletons (adjusted risk ratio [aRR] = 0.46, 95% confidence interval [CI]: 0.26-0.85). Similar results were observed among multiples at <28 weeks of gestation (aRR = 0.64, 95% CI: 0.45-0.89). CONCLUSION: Our findings suggest that ART use is associated with a decreased risk of perinatal deaths prior to 28 weeks of gestation, which may be explained by earlier detection and management of fetal and maternal conditions among ART-conceived pregnancies. These findings provide valuable information for health care providers, including infertility specialists, obstetricians, and pediatricians when counseling ART users on risk of treatment. KEY POINTS: · ART use is associated with a decreased risk of perinatal deaths prior to 28 weeks of gestation.. · ART perinatal mortality rates were lower than that for non-ART perinatal mortality.. · This study used linked data to examine associations between use of ART and perinatal deaths..

Chlamydial Pgp3 Seropositivity and Population-Attributable Fraction Among Women With Tubal Factor Infertility.

BACKGROUND: Chlamydial infection is associated with tubal factor infertility (TFI); however, assessment of prior chlamydial infection and TFI is imperfect. We previously evaluated a combination of serological assays for association with TFI. We now describe the chlamydial contribution to TFI using a newer Chlamydia trachomatis Pgp3-enhanced serological (Pgp3) assay. METHODS: In our case-control study of women 19 to 42 years old with hysterosalpingogram-diagnosed TFI (cases) and non-TFI (controls) in 2 US infertility clinics, we assessed possible associations and effect modifiers between Pgp3 seropositivity and TFI using adjusted odds ratios with 95% confidence intervals (CIs) stratified by race. We then estimated the adjusted chlamydia population-attributable fraction with 95% CI of TFI. RESULTS: All Black (n = 107) and 618 of 620 non-Black women had Pgp3 results. Pgp3 seropositivity was 25.9% (95% CI, 19.3%-33.8%) for non-Black cases, 15.2% (95% CI, 12.3%-18.7%) for non-Black controls, 66.0% (95% CI, 51.7%-77.8%) for Black cases, and 71.7% (95% CI, 59.2%-81.5%) for Black controls. Among 476 non-Black women without endometriosis (n = 476), Pgp3 was associated with TFI (adjusted odds ratio, 2.6 [95% CI, 1.5-4.4]), adjusting for clinic, age, and income; chlamydia TFI-adjusted population-attributable fraction was 19.8% (95% CI, 7.7%-32.2%) in these women. Pgp3 positivity was not associated with TFI among non-Black women with endometriosis or among Black women (regardless of endometriosis). CONCLUSIONS: Among non-Black infertile women without endometriosis in these clinics, 20% of TFI was attributed to chlamydia. Better biomarkers are needed to estimate chlamydia TFI PAF, especially in Black women.

Tubal Factor Infertility, In Vitro Fertilization, and Racial Disparities: A Retrospective Cohort in Two US Clinics.

BACKGROUND: Nearly 14% of US women report any lifetime infertility which is associated with health care costs and psychosocial consequences. Tubal factor infertility (TFI) often occurs as a result of sexually transmitted diseases and subsequent pelvic inflammatory disease. We sought to evaluate for and describe potential racial disparities in TFI and in vitro fertilization (IVF) prevalence. METHODS: Records of women aged 19 to 42 years in our retrospective cohort from 2 US infertility clinics were reviewed. We calculated TFI prevalence, IVF initiation prevalence, and prevalence ratios (PRs), with 95% confidence intervals (CIs) for each estimate, overall and by race. RESULTS: Among 660 infertile women, 110 (16.7%; 95% CI, 13.8-19.5%) had TFI which was higher in Black compared with White women (30.3% [33/109] vs 13.9% [68/489]; PR, 2.2 [95% CI, 1.5-3.1]). For women with TFI, IVF was offered to similar proportions of women by race (51.5% [17/33] vs 52.9% [36/68] for Black vs White women); however, fewer Black than White women with TFI started IVF (6.7% [1/15] vs 31.0% [9/29]; PR, 0.2 [95% CI, 0-1.0]), although the difference was not statistically different. CONCLUSIONS: Tubal factor infertility prevalence was 2-fold higher among Black than White women seeking care for infertility. Among women with TFI, data suggested a lower likelihood of Black women starting IVF than White women. Improved sexually transmitted disease prevention and treatment might ameliorate disparities in TFI.

US State-Level Infertility Insurance Mandates and Health Plan Expenditures on Infertility Treatments.

Objectives We aimed to examine the extent to which health plan expenditures for infertility services differed by whether women resided in states with mandates requiring coverage of such services and by whether coverage was provided through a self-insured plan subject to state mandates versus fully-insured health plans subject only to federal regulation. Methods This retrospective cohort study used individual-level, de-identified health insurance claims data. We included women 19-45 years of age who were continuously enrolled during 2011 and classified them into three mutually exclusive groups based on highest treatment intensity: in vitro fertilization (IVF), intrauterine insemination (IUI), or ovulation-inducing (OI) medications. Using generalized linear models, we estimated adjusted annual mean, aggregate, and per member per month (PMPM) expenditures among women in states with an infertility insurance mandate and those in states without a mandate, stratified by enrollment in a fully-insured or self-insured health plan. Results Of the 6,006,017 women continuously enrolled during 2011, 9199 (0.15%) had claims for IVF, 10,112 (0.17%) had claims for IUI, and 23,739 (0.40%) had claims for OI medications. Among women enrolled in fully insured plans, PMPM expenditures for infertility treatment were 3.1 times higher for those living in states with a mandate compared with states without a mandate. Among women enrolled in self-insured plans, PMPM infertility treatment expenditures were 1.2 times higher for mandate versus non-mandate states. Conclusions for Practice Recorded infertility treatment expenditures were higher in states with insurance reimbursement mandates versus those without mandates, with most of the difference in expenditures incurred by fully-insured plans.

Preterm Birth and Small Size for Gestational Age in Singleton, In Vitro Fertilization Births Using Donor Oocytes.

We used 2006-2015 US National Assisted Reproductive Technology Surveillance System data to compare preterm birth and fetal growth for liveborn singletons (24-42 weeks' gestation) following in vitro fertilization with donor versus autologous oocytes. Using binary and multinomial logistic regression, we computed adjusted odds ratios and 95% confidence intervals for associations between use of donor oocytes and preterm delivery, being small for gestational age (SGA), and being large for gestational age (LGA), stratified by fresh and thawed embryo status and accounting for maternal characteristics and year of birth. There were 204,855 singleton births from fresh embryo transfers and 106,077 from thawed embryo transfers. Among fresh embryo transfers, donor oocyte births had higher odds of being preterm (adjusted odd ratio (aOR) = 1.32, 95% confidence interval (CI): 1.27, 1.38) or LGA (aOR = 1.27, 95% CI: 1.21, 1.33) but lower odds of being SGA (aOR = 0.81, 95% CI: 0.77, 0.85). Among thawed embryo transfers, donor oocyte births had higher odds of being preterm (aOR = 1.57, 95% CI: 1.48, 1.65) or SGA (aOR = 1.22, 95% CI: 1.14, 1.31) but lower odds of being LGA (aOR = 0.87, 95% CI: 0.82, 0.92). Use of donor oocytes was associated with increased odds of preterm delivery irrespective of embryo status; odds of being SGA were increased for donor versus autologous oocyte births among thawed embryo transfers only.

Effect of frozen/thawed embryo transfer on birthweight, macrosomia, and low birthweight rates in US singleton infants.

BACKGROUND: Singleton infants conceived using assisted reproductive technology have lower average birthweights than naturally conceived infants and are more likely to be born low birthweight (<2500 gr). Lower birthweights are associated with increased infant and child mortality and poor adult health outcomes, including cardiovascular disease, hypertension, and diabetes. Data from registry and single-center studies suggest that frozen/thawed embryo transfer may be associated with larger birthweights. To date, however, a nationwide, full-population study on United States infants born using frozen/thawed embryo transfer has not been reported. OBJECTIVES: The objective of this study was to compare the effect of frozen/thawed vs fresh embryo transfer on birthweight outcomes for singleton, term infants conceived using in vitro fertilization in the United States between 2007 and 2014, including average birthweight and the risks of both macrosomia (>4000 g) and low birthweight (<2500 g). STUDY DESIGN: We used data from the Centers for Disease Control and Prevention's National Assisted Reproductive Technology Surveillance System to compare birthweight outcomes of live-born singleton, autologous oocyte, term (37-43 weeks) infants. Generalized linear models for all infants and stratified by infant sex were used to assess the relationship between frozen/thawed embryo transfer and birthweight, in grams. Infertility diagnosis, year of treatment, maternal age, maternal obstetric history, maternal and paternal race, and infant gestational age and sex were included in the models. Missing race data were imputed. The adjusted relative risks for macrosomia and low birthweight were evaluated using multivariable predicted marginal proportions from logistic regression models. RESULTS: In total, 180,184 singleton, term infants were included, with 55,898 (31.02%) having been conceived from frozen/thawed embryos. Frozen/thawed embryo transfer was associated with, on average, a 142 g increase in birthweight compared with infants born after fresh embryo transfer (P < .001). An interaction between infant sex and embryo transfer type was significant (P < .0001), with frozen/thawed embryo transfer having a larger effect on male infants by 16 g. The adjusted risk of a macrosomic infant was 1.70 times higher (95% confidence interval, 1.64-1.76) following frozen/thawed embryo transfer than fresh embryo transfer. However, adjusted risk of low birthweight following frozen/thawed embryo transfer was 0.52 (95% confidence interval, 0.48-0.56) compared with fresh embryo transfer. CONCLUSION: Frozen/thawed embryo transfer, in comparison with fresh embryo transfer, was associated with increased average birthweight in singleton, autologous oocytes, term infants born in the United States, with a significant interaction between frozen/thawed embryo transfer and infant sex. The risk of macrosomia following frozen/thawed embryo transfer was greater than that following fresh embryo transfer, but the risk of low birthweight among frozen/thawed embryo transfer infants was significantly decreased in comparison with fresh embryo transfer infants.

Assisted reproductive technology with donor sperm: national trends and perinatal outcomes.

BACKGROUND: Information regarding the use of donor sperm in assisted reproductive technology, as well as subsequent treatment and perinatal outcomes, remains limited. Outcome data would aid patient counseling and clinical decision making. OBJECTIVES: The objectives of the study were to report national trends in donor sperm utilization and live birth rates of donor sperm-assisted reproductive technology cycles in the United States and to compare assisted reproductive technology treatment and perinatal outcomes between cycles using donor and nondonor sperm. We hypothesize these outcomes to be comparable between donor and nondonor sperm cycles. STUDY DESIGN: This was a retrospective cohort study using data from all US fertility centers reporting to the Centers for Disease Control and Prevention's National Assisted Reproductive Technology Surveillance System, accounting for ∼98% of assisted reproductive technology cycles (definition excludes intrauterine insemination). The number and percentage of assisted reproductive technology cycles using donor sperm and rates of pregnancy, live birth, preterm birth (<37 weeks), and low birthweight (<2500 g) were the primary outcomes measured. Treatments assessed include use of donor vs nondonor sperm. The trends analysis included all banking and fresh assisted reproductive technology cycles using donor and autologous oocytes performed between 1996 and 2014 (n = 1,710,034). The outcomes analysis was restricted to include only fresh autologous cycles performed between 2010 and 2014 (n = 437,569) to focus on cycles with a potential outcome and cycles reflective of current practice, thereby improving the clinical relevance. Cycles canceled prior to retrieval were excluded. Statistical analysis included linear regression to explore polynomial trends and log-binomial regression to estimate relative risk for outcomes among cycles using donor and nondonor sperm. RESULTS: Of all banking and fresh donor and autologous oocyte assisted reproductive technology cycles performed between 1996 and 2014, 74,892 (4.4%) used donor sperm. In 2014, 7351 assisted reproductive technology cycles using donor sperm were performed, as compared with 1763 in 1996 (6.2% vs 3.8% of all cycles). Among all autologous oocyte cycles performed between 2010 and 2014, the live birth rate was lower for donor sperm (27.9%) than nondonor sperm cycles (32.5%); however, after adjustment for maternal age, donor sperm use was associated with an increased likelihood of live birth (adjusted relative risk, 1.06, 95% confidence interval, 1.01-1.10). Per transfer, there was no significant difference in live birth rates for donor vs nondonor sperm (31.9% vs 36.8%; adjusted relative risk, 1.04, 95% confidence interval, 0.998-1.09). Per singleton live birth, there was no significant difference in preterm birth (11.5% vs 11.8%; adjusted relative risk, 0.98, 95% confidence interval, 0.90-1.06); however, low birthweight delivery was slightly lower in donor sperm cycles (8.8% vs 9.4%; adjusted relative risk, 0.91, 95% confidence interval, 0.83-0.99). CONCLUSION: Donor sperm use in assisted reproductive technology has increased in the United States, accounting for approximately 6% of all assisted reproductive technology cycles in 2014. Assisted reproductive technology treatment and perinatal outcomes were clinically similar in donor and nondonor sperm cycles.

Update: Interim Guidance for Preconception Counseling and Prevention of Sexual Transmission of Zika Virus for Men with Possible Zika Virus Exposure - United States, August 2018.

Zika virus infection can occur as a result of mosquitoborne or sexual transmission of the virus. Infection during pregnancy is a cause of fetal brain abnormalities and other serious birth defects (1,2). CDC has updated the interim guidance for men with possible Zika virus exposure who 1) are planning to conceive with their partner, or 2) want to prevent sexual transmission of Zika virus at any time (3). CDC now recommends that men with possible Zika virus exposure who are planning to conceive with their partner wait for at least 3 months after symptom onset (if symptomatic) or their last possible Zika virus exposure (if asymptomatic) before engaging in unprotected sex. CDC now also recommends that for couples who are not trying to conceive, men can consider using condoms or abstaining from sex for at least 3 months after symptom onset (if symptomatic) or their last possible Zika virus exposure (if asymptomatic) to minimize their risk for sexual transmission of Zika virus. All other guidance for Zika virus remains unchanged. The definition of possible Zika virus exposure remains unchanged and includes travel to or residence in an area with risk for Zika virus transmission (https://wwwnc.cdc.gov/travel/page/world-map-areas-with-zika) or sex without a condom with a partner who traveled to or lives in an area with risk for Zika virus transmission. CDC will continue to update recommendations as new information becomes available.

Birthweight in infants conceived through in vitro fertilization following blastocyst or cleavage-stage embryo transfer: a national registry study.

PURPOSE: In vitro fertilization (IVF) infants have lower birthweights than their peers, predisposing them to long-term health consequences. Blastocyst transfer (BT), at day 5-6 post-fertilization, is increasing in usage, partially due to improved pregnancy outcomes over cleavage-stage transfer (CT, day 2-3). Data to date, however, have been inconclusive regarding BT's effects on birthweight. METHODS: Participants included all US autologous, single-gestation, fresh embryo transfer cycles initiated from 2007 to 2014 that resulted in a term infant (N = 124,154) from the National Assisted Reproductive Technology Surveillance System. Generalized linear models including obstetric history, maternal demographics, and infant sex and gestational age were used to compare birthweight outcomes for infants born following BT (N = 67,169) with infants born following CT (N = 56,985) and to test for an interaction between transfer stage and single embryo transfer (SET). RESULTS: Infants born following BT were 6 g larger than those born following CT (p = 0.04), but rates of macrosomia (RR 1.00, 95% CI 0.96-1.04) and low birthweight (LBW, RR 1.00, 95% CI 0.93-1.06) were not different between the groups. The interaction between SET and transfer stage was significant (p = 0.02). Among SET infants, BT was associated with 19.26 g increased birthweight compared to CT (p = 0.008). CONCLUSIONS: The increase in birthweights identified following BT is unlikely to be clinically relevant, as there were no differences in rates of macrosomia or LBW. These findings are clinically reassuring and indicate that the increasing use of BT is unlikely to further decrease the on average lower birthweights seen in IVF infants compared to their naturally conceived peers.

Surgically acquired sperm use for assisted reproductive technology: trends and perinatal outcomes, USA, 2004-2015.

PURPOSE: To compare national trends and perinatal outcomes following the use of ejaculated versus surgically acquired sperm among IVF cycles with male factor infertility. METHODS: This retrospective cohort includes US fertility clinics reporting to the National ART Surveillance System between 2004 and 2015. Fresh, non-donor IVF male factor cycles (n = 369,426 cycles) were included. We report the following outcomes: (1) Trends in surgically acquired and ejaculated sperm. (2) Adjusted risk ratios comparing outcomes for intracytoplasmic sperm injection (ICSI) cycles using surgically acquired (epididymal or testicular) versus ejaculated sperm. (3) Outcomes per non-canceled cycle: biochemical pregnancy, intrauterine pregnancy, and live birth (≥ 20 weeks). (4) Outcomes per pregnancy: miscarriage (< 20 weeks) and singleton pregnancy. (5) Outcomes per singleton pregnancy: normal birthweight (≥ 2500 g) and full-term delivery (≥ 37 weeks). RESULTS: Percentage of male factor infertility cycles that used surgically acquired sperm increased over the study period, 9.8 (2004) to 11.6% (2015), p < 0.05. The proportion of cycles using testicular sperm increased significantly over the study period, 4.9 (2004) to 6.5% (2015), p < 0.05. Among fresh, non-donor male factor ART cycles which used ICSI (n = 347,078 cycles), cycle, pregnancy, and perinatal outcomes were statistically significant but clinically similar with confidence intervals approaching one between cycles involving epididymal versus ejaculated sperm and between testicular versus ejaculated sperm. Results were similar among cycles with a sole diagnosis of male factor (no female factors), and for the subset in which the female partner was < 35 years old. CONCLUSION: Among couples undergoing ART for treatment of male factor infertility, pregnancy and perinatal outcomes were similar between cycles utilizing ejaculated sperm or surgically acquired testicular and epididymal sperm.

Trends in Testosterone Replacement Therapy Use from 2003 to 2013 among Reproductive-Age Men in the United States.

PURPOSE: Although testosterone replacement therapy use in the United States has increased dramatically in the last decade, to our knowledge trends in testosterone replacement therapy use among reproductive-age men have not been investigated. We assessed changes in testosterone replacement therapy use and practice patterns among 18 to 45-year-old American men from 2003 to 2013 and compared them to older men. MATERIALS AND METHODS: This is a retrospective, cross-sectional analysis of men 18 to 45 and 56 to 64 years old who were enrolled in the Truven Health MarketScan® Commercial Claims Databases throughout each given calendar year from 2003 to 2013, including 5,094,868 men in 2013. Trends in the yearly rates of testosterone replacement therapy use were calculated using Poisson regression. Among testosterone replacement therapy users, the Cochran-Armitage test was used to assess temporal trends in age, formulation type, semen analysis and serum testosterone level testing during the 12 months preceding the documented use of testosterone replacement therapy. RESULTS: Between 2003 and 2013, there was a fourfold increase in the rate of testosterone use among 18 to 45-year-old men from 29.2/10,000 person-years to 118.1/10,000 person-years (p <0.0001). Among testosterone replacement therapy users, topical gel formulations were initially most used. Injection use then doubled between 2009 and 2012 (23.5% and 46.2%, respectively) and surpassed topical gel use in 2013. In men 56 to 64 years old there was a statistically significant threefold increase in testosterone replacement therapy use (p <0.0001), which was significantly smaller than the fourfold increase in younger men (p <0.0001). CONCLUSIONS: In 2003 to 2013, testosterone replacement therapy use increased fourfold in men 18 to 45 years old compared to threefold in older men. This younger age group should be a focus for future studies due to effects on fertility and unknown long-term sequelae.

Population-attributable fraction of tubal factor infertility associated with chlamydia.

BACKGROUND: Chlamydia trachomatis infection is highly prevalent among young women in the United States. Prevention of long-term sequelae of infection, including tubal factor infertility, is a primary goal of chlamydia screening and treatment activities. However, the population-attributable fraction of tubal factor infertility associated with chlamydia is unclear, and optimal measures for assessing tubal factor infertility and prior chlamydia in epidemiological studies have not been established. Black women have increased rates of chlamydia and tubal factor infertility compared with White women but have been underrepresented in prior studies of the association of chlamydia and tubal factor infertility. OBJECTIVES: The objectives of the study were to estimate the population-attributable fraction of tubal factor infertility associated with Chlamydia trachomatis infection by race (Black, non-Black) and assess how different definitions of Chlamydia trachomatis seropositivity and tubal factor infertility affect population-attributable fraction estimates. STUDY DESIGN: We conducted a case-control study, enrolling infertile women attending infertility practices in Birmingham, AL, and Pittsburgh, PA, during October 2012 through June 2015. Tubal factor infertility case status was primarily defined by unilateral or bilateral fallopian tube occlusion (cases) or bilateral fallopian tube patency (controls) on hysterosalpingogram. Alternate tubal factor infertility definitions incorporated history suggestive of tubal damage or were based on laparoscopic evidence of tubal damage. We aimed to enroll all eligible women, with an expected ratio of 1 and 3 controls per case for Black and non-Black women, respectively. We assessed Chlamydia trachomatis seropositivity with a commercial assay and a more sensitive research assay; our primary measure of seropositivity was defined as positivity on either assay. We estimated Chlamydia trachomatis seropositivity and calculated Chlamydia trachomatis-tubal factor infertility odds ratios and population-attributable fraction, stratified by race. RESULTS: We enrolled 107 Black women (47 cases, 60 controls) and 620 non-Black women (140 cases, 480 controls). Chlamydia trachomatis seropositivity by either assay was 81% (95% confidence interval, 73-89%) among Black and 31% (95% confidence interval, 28-35%) among non-Black participants (P < .001). Using the primary Chlamydia trachomatis seropositivity and tubal factor infertility definitions, no significant association was detected between chlamydia and tubal factor infertility among Blacks (odds ratio, 1.22, 95% confidence interval, 0.45-3.28) or non-Blacks (odds ratio, 1.41, 95% confidence interval, 0.95-2.09), and the estimated population-attributable fraction was 15% (95% confidence interval, -97% to 68%) among Blacks and 11% (95% confidence interval, -3% to 23%) among non-Blacks. Use of alternate serological measures and tubal factor infertility definitions had an impact on the magnitude of the chlamydia-tubal factor infertility association and resulted in a significant association among non-Blacks. CONCLUSION: Low population-attributable fraction estimates suggest factors in addition to chlamydia contribute to tubal factor infertility in the study population. However, high background Chlamydia trachomatis seropositivity among controls, most striking among Black participants, could have obscured an association with tubal factor infertility and resulted in a population-attributable fraction that underestimates the true etiological role of chlamydia. Choice of chlamydia and tubal factor infertility definitions also has an impact on the odds ratio and population-attributable fraction estimates.

Effects of Antiretroviral Therapy to Prevent HIV Transmission to Women in Couples Attempting Conception When the Man Has HIV Infection - United States, 2017.

Existing U.S. guidelines recommend that men with human immunodeficiency virus (HIV) infection should achieve virologic suppression* with effective antiretroviral therapy (ART) before attempting conception (1). Clinical studies have demonstrated that effective ART profoundly reduces the risk for HIV transmission (2-4). This information might be useful for counseling couples planning a pregnancy in which the man has HIV infection and the woman does not (i.e., a mixed HIV-status couple, often referred to as a serodiscordant couple).

Strategies for Preventing HIV Infection Among HIV-Uninfected Women Attempting Conception with HIV-Infected Men - United States.

By the end of 2014, a total of 955,081 persons in the United States (299.5 per 100,000 population) had received a diagnosis of human immunodeficiency virus type 1 (HIV-1) infection (1). The annual estimated number of HIV infections and incidence rate in the United States decreased from 2010 to 2014, and the survival rate has increased over time (1). Effective highly active antiretroviral therapy (HAART) is helping persons with HIV to live longer, healthier lives. Many of these persons, including an unknown percentage in discordant relationships (i.e., one partner is HIV-infected, and the other is HIV-uninfected), might wish to have their own biologic children. When the female partner is HIV-infected and the male partner is not, a discordant couple can undergo autologous sperm intrauterine inseminations to achieve conception without placing the man at risk for infection. However, for HIV-discordant couples in which the man is HIV-infected and the woman is not, strategies to minimize the risk for sexual transmission are needed. In 1988, CDC recommended against insemination with semen from HIV-infected men (2). Since 1988, new information has emerged regarding prevention of HIV transmission in HIV-discordant couples. This report reviews laboratory and epidemiologic information regarding the prevention of HIV transmission for HIV-discordant couples, in which the male is HIV-infected and the female is HIV-uninfected, who would like to attempt conception.

Affordability of Fertility Treatments and Multiple Births in the United States.

BACKGROUND: Affordability plays an important role in the utilisation of in vitro fertilisation (IVF) and non-IVF fertility treatments. Fertility treatments are associated with increased risk of multiple births. The objective of this study was to investigate the association between the affordability of fertility treatments across US states and the percentage of multiple births due to natural conception, non-IVF treatments, and IVF, and the association between these percentages and state-specific multiple birth rates. METHODS: State-specific per capita disposable personal income and state-specific infertility insurance mandates were used as measures of affordability. Maternal age-adjusted percentages of multiple births due to natural conception, non-IVF treatments, and IVF were estimated for each state using birth certificate and IVF data. Scatter plots and regression analysis were used to explore associations between state-level measures of affordability, the percentage of multiple births due to natural conception and fertility treatments, and state-specific multiple birth rates. RESULTS: In 2013, age-adjusted contributions of natural conception, non-IVF fertility treatments, and IVF to multiple births in US were 58.2, 22.8, and 19.0% respectively. States with greater affordability of fertility treatments had higher percentages of multiples due to IVF and lower percentages due to natural conception. Higher percentages of multiples due to IVF and lower percentages due to natural conception were associated with higher state-specific multiple birth rates. CONCLUSION: Increasing affordability of fertility treatments may increase state-specific multiple birth rates. Policies and treatment practices encouraging single-gestation pregnancies may help reduce multiple births resulting from these treatments.

Health-Related Quality of Life for Women Ever Experiencing Infertility or Difficulty Staying Pregnant.

INTRODUCTION: Information on the health-related quality of life (HRQOL) for women with infertility is limited and does not account for the co-occurrence of chronic conditions or emotional distress. METHODS: We used data from state-added questions on reproductive health included in the 2013 Behavioral Risk Factor Surveillance System in seven states. HRQOL indicators included: self-reported health status; number of days in the past 30 days when physical and mental health was not good; number of days in the past 30 days that poor physical or mental health limited activities. We computed rate ratios for HRQOL for women ever experiencing infertility or difficulty staying pregnant compared with women never reporting these conditions; interactions with chronic conditions and depressive disorders were assessed. RESULTS: Of 7,526 respondents aged 18-50 years, 387 (4.9%) reported infertility only and 339 (4.3%) reported difficulty staying pregnant only. Infertility was associated with an increase in average number of days with poor physical health for women with chronic conditions [rate ratio (RR) 1.85, 95% confidence interval (CI) 1.04-3.29] but was protective for women without chronic conditions (RR 0.47, 95% CI 0.29-0.75). Difficulty staying pregnant was associated with an increase in average number of days of limited activity among both women with chronic conditions (RR 2.14, 95% CI 1.32-3.45) and women with depressive disorders (RR 1.72 95% CI 1.14-2.62). DISCUSSION: Many HRQOL measures were poorer for women who had infertility or difficulty staying pregnant compared to their counterparts; the association was modified by presence of chronic conditions and depressive disorders.