Gary Jeng

Does assisted hatching pose a risk for monozygotic twinning in pregnancies conceived through in vitro fertilization

OBJECTIVE To examine the association between assisted hatching and monozygotic (MZ) twinning. DESIGN Case-control. SETTING Population-based sample of IVF-ET cycles initiated in U.S. clinics, 1996. PATIENT(S) The IVF-ET (n = 35,503) cycles and 11,247 resultant pregnancies. INTERVENTION(S) Use of an assisted hatching procedure on embryos transferred. MAIN OUTCOME MEASURE(S) Cases were pregnancies for which number of fetal hearts observed on ultrasound exceeded number of embryos transferred. These pregnancies were considered to contain at least one MZ set of twins. Cases were compared with two control groups: other multiple-gestation pregnancies (>/=2 fetal hearts but number of fetal hearts </= number of embryos transferred); and singleton pregnancies (1 fetal heart). RESULT(S) Women with a case pregnancy were more likely to have received embryos treated with assisted hatching procedures than were women in either control group. After adjustment for patient age, number of embryos transferred, prior cycles, infertility diagnosis, intracytoplasmic sperm injection, and whether embryos from the current cycle were cryopreserved for later use, odds ratios and 95% CIs for use of assisted hatching were 3.2 (1.2-8.0), compared with other multiple-gestation pregnancies, and 3.8 (1.8-9.8), compared with singleton pregnancies. CONCLUSION(S) Assisted hatching may pose a risk for MZ twinning.

Does insurance coverage decrease the risk for multiple births associated with assisted reproductive technology

OBJECTIVE To determine whether insurance coverage for ART is associated with transfer of fewer embryos and decreased risk of multiple births. DESIGN Retrospective cohort study of a population-based sample of IVF procedures performed in six U.S. states during 1998. SETTING Three states with mandated insurance coverage (Illinois, Massachusetts, and Rhode Island) and three states without coverage (Indiana, Michigan, and New Jersey). PARTICIPANT(S) Seven thousand, five hundred sixty-one IVF transfer procedures in patients < or = 35 years of age. MAIN OUTCOME MEASURE(S) Number of embryos transferred, multiple-birth rate, triplet or higher order birth rate, and triplet or higher order gestation rate. RESULT(S) A smaller proportion of procedures included transfer of three or more embryos in Massachusetts (64%) and Rhode Island (74%) than in the noninsurance states (82%). The multiple-birth rate in Massachusetts (38%) was less than in the noninsurance states (43%). The insurance states all had protective odds ratios for triplet or higher order births, but only the odds ratio (0.2) for Massachusetts was significant. This decreased risk in Massachusetts resulted from several factors, including a smaller proportion of patients with three or more embryos transferred, lower implantation rates when three or more embryos were transferred, and greater rates of fetal loss among triplet or higher order gestations. CONCLUSION(S) Insurance appears to affect embryo transfer practices. Whether this translates into decreased multiple birth risk is less clear.

The risk of menstrual abnormalities after tubal sterilization.

BACKGROUND The existence of a post-tubal-ligation syndrome of menstrual abnormalities has been debated for decades. We used data from the U.S. Collaborative Review of Sterilization to determine whether the likelihood of persistent menstrual abnormalities was greater among women who had undergone tubal sterilization than among women who had not. METHODS A total of 9514 women who underwent tubal sterilization and 573 women whose partners underwent vasectomy were followed in a multicenter, prospective cohort study for up to five years by means of annual telephone interviews. All women were asked the same questions about six characteristics of their menstrual cycles in the presterilization and follow-up interviews. Multiple logistic-regression analysis was used to assess the risk of persistent menstrual changes. RESULTS The women who had undergone sterilization were no more likely than those who had not undergone the procedure to report persistent changes in intermenstrual bleeding or the length of the menstrual cycle. They were more likely to have decreases in the number of days of bleeding (odds ratio, 2.4; 95 percent confidence interval, 1.1 to 5.2), the amount of bleeding (odds ratio, 1.5; 95 percent confidence interval, 1.1 to 2.0), and menstrual pain (odds ratio, 1.3; 95 percent confidence interval, 1.0 to 1.8) and to have an increase in cycle irregularity (odds ratio, 1.6; 95 percent confidence interval, 1.1 to 2.3). Among women who had had very heavy bleeding at base line, women who had undergone sterilization were more likely than women who had not undergone the procedure to report decreased bleeding (45 percent vs. 33 percent, P=0.03). CONCLUSIONS Women who have undergone tubal sterilization are no more likely than other women to have menstrual abnormalities.

Spontaneous abortion among pregnancies conceived using assisted reproductive technology in the United States.

OBJECTIVE To examine rates and risk factors for spontaneous abortion among pregnancies conceived using assisted reproductive technology (ART). METHODS Subjects were 62,228 clinical pregnancies resulting from ART procedures initiated in 1996–1998 in US clinics. Spontaneous abortion was based on ART clinic report and was defined as loss of the entire pregnancy. Spontaneous abortion rates for ART pregnancies were compared with spontaneous abortion rates from the National Survey of Family Growth, a population-based survey of US women 15–44 years. RESULTS The spontaneous abortion rate among ART pregnancies was 14.7%. This was similar to rates among pregnancies reported in the National Survey of Family Growth. Among pregnancies conceived with the patients oocytes and freshly fertilized embryos, the spontaneous abortion risk ranged from 10.1% among women 20–29 years to 39.3% among women older than 43. Spontaneous abortion risk among pregnancies conceived with donor eggs was 13.1% with little variation by patient age. Spontaneous abortion risk was increased for pregnancies conceived with frozen and thawed embryos and decreased among multiple-gestation pregnancies. Spontaneous abortion risk was increased among women reporting previous spontaneous abortions and ART attempts, and among women who used clomiphene or zygote intrafallopian transfer. Pregnancies conceived by young women, but gestated by a surrogate, were at increased risk for spontaneous abortion in comparison with young women who gestated their own pregnancies. CONCLUSION These findings suggest that ART does not pose a risk for spontaneous abortion. Factors related to oocyte or embryo quality are of primary importance in assessing spontaneous abortion risk.

Requesting information about and obtaining reversal after tubal sterilization: findings from the U.S. Collaborative Review of Sterilization

OBJECTIVE To determine the cumulative probabilities over 14 y of requesting information on sterilization reversal and of obtaining a reversal and to identify risk factors observable at sterilization for both measures of regret. DESIGN The U.S. Collaborative Review of Sterilization, a prospective cohort study. SETTING Fifteen medical centers in 9 cities. PATIENT(S) 11,232 women. MAIN OUTCOME MEASURE(S) Cumulative probabilities of requesting information on reversal and undergoing reversal. RESULT(S) The 14-y cumulative probability of requesting reversal information was 14.3% (95% confidence interval [CI], 12.4%-16.3%). Among women aged 18 to 24 y at sterilization, the cumulative probability was 40.4% (95% CI, 31.6%-49.2%). Women aged 18 to 24 y were almost 4 times as likely to request reversal information as were women > or = 30 years of age (adjusted rate ratio [RR], 3.5; 95% CI, 2.8-4.4). Number of living children was not associated with requesting reversal information. The overall cumulative probability of obtaining reversal was 1.1% (95% CI, 0.5-1.6). Younger women (18 to 30 y) were more likely to obtain reversal (RR, 7.6; 95% CI, 3.2-18.3). CONCLUSION(S) Women who were sterilized at a young age had a high chance of later requesting information about reversal, regardless of their number of living children.

Outcomes of in vitro fertilization with preimplantation genetic diagnosis: an analysis of the United States Assisted Reproductive Technology Surveillance Data, 2011–2012

OBJECTIVE To assess the characteristics of IVF cycles for which preimplantation genetic diagnosis (PGD) was used and to evaluate indications for PGD and treatment outcomes associated with this procedure as compared with cycles without PGD with the data from the U.S. National ART Surveillance System. DESIGN Retrospective cohort study. SETTING None. PATIENT(S) Fresh autologous cycles that involved transfer of at least one embryo at blastocyst when available. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) PGD indications and age-specific reproductive outcomes. RESULT(S) There were a total of 97,069 non-PGD cycles and 9,833 PGD cycles: 55.6% were performed for aneuploidy screening (PGD Aneuploidy), 29.1% for other reasons (PGD Other), and 15.3% for genetic testing (PGD Genetic). In comparison to non-PGD cycles, PGD Aneuploidy cycles showed a decreased odds of miscarriage among women 35-37 years (adjusted odds ratio [aOR] 0.62; 95% CI, 0.45-0.87) and women >37 years (aOR 0.55; 95% CI, 0.43-0.70); and an increased odds of clinical pregnancy (aOR 1.18; 95% CI, 1.05-1.34), live-birth delivery (aOR 1.43; 95% CI, 1.26-1.62), and multiple-birth delivery (aOR 1.98; 95% CI, 1.52-2.57) among women >37 years. CONCLUSION(S) Aneuploidy screening was the most common indication for PGD. Use of PGD was not observed to be associated with an increased odds of clinical pregnancy or live birth for women <35 years. PGD for aneuploidy was associated with a decreased odds of miscarriage for women >35 years, but an increased odds of a live-birth and a multiple live-birth delivery among women >37 years.

Oral contraceptive formulation and risk of breast cancer

BACKGROUND While evidence on the association between oral contraceptive (OC) use and breast cancer generally suggests little or no increased risk, the question of whether breast cancer risk varies by OC formulation remains controversial. Few studies have examined this issue because large samples and extensive OC histories are required. STUDY DESIGN We used data from a multicenter, population-based, case-control investigation. Women aged 35-64 years were interviewed. To explore the association between OC formulation and breast cancer risk, we used conditional logistic regression to derive adjusted odds ratios, and we used likelihood ratio tests for heterogeneity to assess whether breast cancer risk varied by OC formulation. Key OC exposure variables were ever use, current or former use, duration of use and time since last use. To strengthen inferences about specific formulations, we restricted most analyses to the 2282 women with breast cancer and the 2424 women without breast cancer who reported no OC use or exclusive use of one OC. RESULTS Thirty-eight formulations were reported by the 2674 women who used one OC; most OC formulations were used by only a few women. We conducted multivariable analyses on the 10 formulations that were each used by at least 50 women and conducted supplemental analyses on selected formulations of interest based on recent research. Breast cancer risk did not vary significantly by OC formulation, and no formulation was associated with a significantly increased breast cancer risk. CONCLUSIONS These results add to the small body of literature on the relationship between OC formulation and breast cancer. Our data are reassuring in that, among women 35-64 years of age, we found no evidence that specific OC formulations increase breast cancer risk.

Treatment of bleeding irregularities in women with copper-containing IUDs: a systematic review

BACKGROUND Bleeding irregularities, such as intermenstrual spotting or heavy or prolonged menstrual bleeding, are common among copper-containing intrauterine device (Cu-IUD) users and are one of the leading reasons for method discontinuation. This review evaluates the evidence for effective therapeutic and preventive treatments for bleeding irregularities during Cu-IUD use. STUDY DESIGN We searched the PubMed database for peer-reviewed articles that were published in any language from inception of the database through March 2012 and were relevant to treatments for irregular bleeding during Cu-IUD use. We used standard abstract forms and grading systems to summarize and assess the quality of the evidence. RESULTS From 1470 articles, we identified 17 articles that met our inclusion criteria. Evidence from two studies of poor quality demonstrated that antifibrinolytic agents or nonsteroidal anti-inflammatory drugs (NSAIDs) have been used for intermenstrual bleeding or spotting among a small number of Cu-IUD users with mixed results. Evidence from 10 studies of fair to poor quality suggested that some NSAIDs may significantly reduce menstrual blood loss or bleeding duration among Cu-IUD users with heavy or prolonged menstrual bleeding. Antifibrinolytic drugs or antidiuretics may also help reduce blood loss. High-dose aspirin was shown to increase blood loss among those with baseline menorrhagia. Evidence from five studies of fair to poor quality suggested that bleeding irregularities among new Cu-IUD users may be prevented with NSAIDs, although one large study of good quality suggested that prophylactic treatment with ibuprofen does not affect continuation of Cu-IUD use. Evidence from two studies of fair to poor quality suggested that antifibrinolytic agents might be helpful in preventing heavy or prolonged menstrual bleeding among new Cu-IUD users. CONCLUSIONS Limited evidence suggests that NSAIDs may be effective treatments for bleeding irregularities associated with Cu-IUD use; antifibrinolytic agents and antidiuretics have also been studied as possible treatments in a small number of subjects, but their safety has not been well documented. NSAIDs and antifibrinolytics may also prevent bleeding irregularities among new CU-IUD users. Preventive NSAID use, however, does not impact Cu-IUD continuation.

Linking Birth and Infant Death Records With Assisted Reproductive Technology Data: Massachusetts, 1997–1998

Objectives: To link data from the US assisted reproductive technology (ART) registry with the Massachusetts birth–infant death file to create a comprehensive dataset on the circumstances surrounding conception and maternal and infant outcomes for a population of ART-conceived infants. Methods: The authors sought to link data for 3704 ART-conceived live-born infants from 2703 deliveries in 1997–1998 involving Massachusetts resident mothers who gave birth in Massachusetts, Rhode Island, New Hampshire, or Connecticut to their corresponding Massachusetts birth record using a two-stage algorithm. Maternal and infant dates of birth served as the primary linkage variables. Maternal names for a subset of the ART-conceived infants were obtained and used in the second stage of the algorithm to confirm a sample of records that matched in Stage I, to resolve duplicate matches, and to link unmatched records. Results: In Stage I, 78% of ART deliveries matched with only one Massachusetts record, 2% matched with two records, and 20% remained unmatched. Overall, the complete algorithm using maternal name data for a portion of records yielded an 89% linkage rate. Nearly all of the records that matched during Stage I that were evaluated with maternal name data in Stage II were confirmed as correctly linked. Conclusions: This project confirms that high-yield data linkage can be achieved in the absence of specific identifiers (e.g., name and social security number). Nonetheless, additional matches were achieved when name data were obtained. This linkage creates the first population-based file in the US capturing detailed information on ART births.

Associations of hormonal contraceptive use with measures of HIV disease progression and antiretroviral therapy effectiveness.

OBJECTIVE To examine the associations between hormonal contraceptive use and measures of HIV disease progression and antiretroviral treatment (ART) effectiveness. STUDY DESIGN A prospective cohort study of women with prevalent HIV infection in St. Petersburg, Russia, was conducted. After contraceptive counseling, participants chose to use combined oral contraceptives (COCs), depot-medroxyprogesterone acetate (DMPA), a copper intrauterine device (IUD) or male condoms for pregnancy prevention. Among participants not using ART at enrollment, we used multivariate Cox regression to assess the association between current (time-varying) contraceptive use and disease progression, measured by the primary composite outcome of CD4 decline to <350 cells/mm(3), ART initiation or death. Among participants using ART at enrollment, we used linear mixed models to estimate the predicted mean CD4 change at select time points by contraceptive method. RESULTS During a total of 5233 months follow-up among participants not using ART with enrollment CD4 ≥350 cells/mm(3) (n=315), 97 experienced disease progression. Neither current use of COCs [adjusted hazard ratio (aHR) 0.91, 95% confidence interval (CI) 0.56-1.48] nor DMPA (aHR 1.28, 95% CI 0.71-2.31) was associated with a statistically significant increased risk for disease progression compared with use of nonhormonal methods (IUD or condoms). Among participants using ART at enrollment (n=77), we found no statistically significant differences in the predicted mean changes in CD4 cell count comparing current use of COCs (p=.1) or DMPA (p=.3) with nonhormonal methods. CONCLUSION Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection. IMPLICATIONS Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection.