Judy E. Stern

Female obesity adversely affects assisted reproductive technology (ART) pregnancy and live birth rates

BACKGROUND Obesity has risen among women in the USA, including those seeking infertility treatments. In 2007, height and weight were added to the Society for Assisted Reproductive Technology Clinic Online Reporting System (SART CORS), permitting calculation of BMI (weight/height(2)) for the first time using this national dataset. METHODS The SART CORS was used to evaluate the odds of failure to achieve a clinical intrauterine pregnancy and failure to achieve a live birth by the womans age, BMI and oocyte source (autologous versus donor), controlling for race and ethnicity, day of embryo transfer, number of embryos transferred and infertility diagnoses. The reference population was women with normal BMI. RESULTS There were 45 163 ART embryo transfers where maternal height and weight were recorded. Increasing obesity was associated with a significant rise in failure to achieve a clinical pregnancy with the use of autologous oocytes (P< 0.0001), but no difference with the use of donor oocytes. Among women using autologous oocytes who did conceive, failure to achieve a live birth increased with increasing obesity, to a greater extent among women <35 years of age. CONCLUSIONS Higher BMI is associated with an increased failure to achieve a clinical intrauterine gestation; this risk was overcome with the use of donor oocytes. Failure to achieve a live birth increases with higher BMI, significantly with the use of autologous oocytes (P< 0.0001), and to a greater extent among women <35 years of age (P< 0.0001).

The effect of increasing obesity on the response to and outcome of assisted reproductive technology: a national study

OBJECTIVE To evaluate the effect of increasing female obesity on response to and outcome of assisted reproductive technology (ART) treatment. DESIGN Historical cohort study. SETTING Clinic-based data. PATIENT(S) A total of 152,500 ART cycle starts from the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System for 2007-2008, limited to women with documented height and grouped by body mass index (BMI, [weight/height(2)]). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Cycle cancellation overall, cycle cancellation due to low response, treatment failure (not pregnant vs. pregnant), and pregnancy failure (fetal loss or stillbirth vs. live birth), as adjusted odds ratios and 95% confidence intervals, with cycles among normal-weight women as the reference group. RESULT(S) Cycle cancellation overall and cancellation due to low response using autologous oocytes significantly paralleled increasing BMI. The odds of treatment failure rose significantly with autologous-fresh cycles, from 1.03 for cycles among overweight women (BMI 25.0-29.9) to 1.53 for cycles among women with BMIs ≥ 50.0 kg/m(2). Likewise, the odds of pregnancy failure were most significant with increasing BMI among women with autologous-fresh cycles, increasing from 1.10 for cycles to overweight women to 2.29 for cycles to women with BMI ≥ 50.0 kg/m(2). CONCLUSION(S) These results indicate significantly higher odds of cycle cancellation. In addition, treatment and pregnancy failures with increasing obesity significantly increased starting with overweight women.

Standardization of grading embryo morphology

Standardization of morphologic assessment for an embryo grading system was developed and is being implemented by the Society for Assisted Reproductive Technology (SART). A recent European consensus conference of embryologists from Europe and America is working toward adopting an embryo classification system modeled similarly to that of SART that, if adopted, would produce a de facto international standard to aid cross-border collaboration.

National collection of embryo morphology data into Society for Assisted Reproductive Technology Clinic Outcomes Reporting System: associations among day 3 cell number, fragmentation and blastomere asymmetry, and live birth rate

OBJECTIVE To evaluate the validity of collecting day 3 embryo morphology variables into the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System (SART CORS). DESIGN Retrospective. SETTING National database-SART CORS. PATIENT(S) Fresh autologous assisted reproductive technology (ART) cycles from 2006-2007 in which embryos were transferred singly (n=1,020) or in pairs (n=6,508) and embryo morphology was collected. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Relationship between live birth, maternal age, and morphology of transferred day 3 embryos as defined by cell number, fragmentation, and blastomere symmetry. Logistic multiple regressions and receiver operating characteristic curve analyses were applied to determine specificity and sensitivity for correctly classifying embryos as either failures or successes. RESULT(S) Live birth rate was positively associated with increasing cell number up to eight cells (<6 cells: 2.9%; 6 cells: 9.6%; 7 cells: 15.5%; 8 cells: 24.3%; and >8 cells: 16.2%), but was negatively associated with maternal age, increasing fragmentation, and asymmetry scores. An area under the receiver operating curve of 0.753 (95% confidence interval 0.740-0.766) was derived, with a sensitivity of 45.0%, a specificity of 83.2%, and 76.4% of embryos being correctly classified with a cutoff probability of 0.3. CONCLUSION(S) This analysis provides support for the validity of collecting morphology fields for day 3 embryos into SART CORS. Standardization of morphology collections will assist in controlling for embryo quality in future database analyses.

Racial and ethnic disparities in assisted reproductive technology pregnancy and live birth rates within body mass index categories

OBJECTIVE To evaluate the effect of maternal race and ethnicity within body mass index (BMI) categories on assisted reproduction technology (ART) pregnancy and live birth rates. DESIGN Historical cohort study. SETTING Clinic-based data. PATIENT(S) 31,672 ART embryo transfers from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System for 2007, limited to women with documented race, ethnicity, height, and weight, with women grouped as white, Asian, Hispanic, or black and by BMI. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Failure to achieve a clinical intrauterine gestation and failure to achieve a live birth as adjusted odds ratios within BMI categories overall with normal-weight women as the reference group, and by race and ethnicity with white women as the reference group. RESULT(S) Failure to achieve a clinical intrauterine gestation was significantly more likely among obese women overall (1.22), normal-weight and obese Asian women (1.36 and 1.73, respectively), normal-weight Hispanic women (1.21), and overweight and obese black women (1.34 and 1.47, respectively). Among women who did conceive, failure to achieve a live birth was significantly more likely among overweight and obese women overall (1.16 and 1.27, respectively), overweight and obese Asian women (1.56 and 2.20, respectively) and Hispanic women (1.57 and 1.76, respectively), and normal-weight and obese black women (1.45 and 1.84, respectively). CONCLUSION(S) These findings indicate significant disparities in pregnancy and live birth rates by race and ethnicity, even within BMI categories.

Practice patterns and outcomes with the use of single embryo transfer in the United States

OBJECTIVE To evaluate factors associated with the use of elective single embryo transfer (eSET) and its effect on assisted reproductive technology (ART) outcome. DESIGN Historical cohort. SETTING Clinic-based data. PATIENT(S) A total of 69,028 ART cycles of autologous fresh embryo transfers with additional embryos cryopreserved during the same cycle performed during 2004-06 and reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Factors associated with the number of embryos transferred, and the odds of pregnancy, live birth, and multiple-infant live birth by number of embryos transferred as adjusted odds ratios (AORs). RESULT(S) Single embryo transfer was used more with uterine factor (AOR 1.76) and less with male factor, endometriosis, or tubal factor (AOR 0.81, 0.72, 0.83, respectively). Compared with women aged <30 years, eSET was used less among women aged 35-39 years and > or =40 years (AOR 0.74 and 0.39, respectively). Compared with White women, eSET was used more with Asian (AOR 1.52) and less with Black or Hispanic women (AOR 0.73 and 0.67, respectively). Compared with eSET, the likelihood of pregnancy, live birth, or multiple-infant live birth was more likely with two embryos (AOR 1.33, 1.34, and 27.4, respectively). CONCLUSION(S) Elective SET, used more for younger women with specific diagnoses, is associated with slightly reduced likelihood of a live birth but much reduced likelihood of multiples.

Use of preimplantation genetic diagnosis and preimplantation genetic screening in the United States: a Society for Assisted Reproductive Technology Writing Group paper.

OBJECTIVE To comprehensively report Society for Assisted Reproductive Technology (SART) member program usage of preimplantation genetic testing (PGT), preimplantation genetic diagnosis (PGD) for diagnosis of specific conditions, and preimplantation genetic screening for aneuploidy (PGS). DESIGN Retrospective study. SETTING United States SART cohort data. PATIENT(S) Women undergoing a PGT cycle in which at least one embryo underwent biopsy. INTERVENTION(S) PGT. MAIN OUTCOME MEASURE(S) PGT use, indications, and delivery rates. RESULT(S) Of 190,260 fresh, nondonor assisted reproductive technology (ART) cycles reported to SART CORS in 2007-2008, 8,337 included PGT. Of 6,971 cycles with a defined indication, 1,382 cycles were for genetic diagnosis, 3,645 for aneuploidy screening (PGS), 527 for translocation, and 1,417 for elective sex election. Although the total number of fresh, autologous cycles increased by 3.6% from 2007 to 2008, the percentage of cycles with PGT decreased by 5.8% (4,293 in 2007 and 4,044 in 2008). As a percentage of fresh, nondonor ART cycles, use dropped from 4.6% (4,293/93,433) in 2007 to 4.2% (4,044/96,827) in 2008. The primary indication for PGT was PGS: cycles performed for this indication decreased (-8.0%). PGD use for single-gene defects (+3.2%), elective sex selection (+5.3%), and translocation analysis (+0.5%) increased. PGT usage varied significantly by geographical region. CONCLUSION(S) PGT usage in the United States decreased between 2007 and 2008 owing to a decrease in PGS. Use of elective sex selection increased. High transfer cancellation rates correlated with reduced live-birth rates for some PGT indications.

National study of factors influencing assisted reproductive technology outcomes with male factor infertility

OBJECTIVE To evaluate the outcomes of assisted reproductive technology (ART) cycles for male factor infertility, and method of sperm collection. DESIGN Historic cohort study. SETTING Clinic-based data. PATIENTS Cycles from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System database for 2004 to 2008 were limited to three groups: non-intracytoplasmic sperm injection (ICSI) and ICSI cycles for tubal ligation only; non-ICSI and ICSI cycles for male factor infertility only; and all cycles (regardless of infertility diagnosis) using ICSI only. INTERVENTION(S) AND MAIN OUTCOME MEASURE(S) Multivariate logistic regression was used to model the adjusted odds ratio (AOR) of clinical intrauterine gestation (CIG) and live birth (LB) rates for tubal ligation versus male factor infertility only; ICSI versus non-ICSI for male factor infertility only; and ICSI outcomes based on method of sperm collection. RESULT(S) Models for male factor infertility only versus tubal ligation only ICSI cycles had lower CIG (AOR 0.92) but not LB (AOR 0.87). No difference was seen for non-ICSI cycles. Within male factor infertility only cycles, ICSI had a worse outcome than non-ICSI for CIG (AOR 0.93) but not for LB (AOR 0.94). For all ICSI cycles with no male factor infertility and ejaculated sperm as the reference group, models showed better rates of CIG with male factor infertility ejaculated sperm (AOR 1.07) and with male factor infertility aspirated sperm (AOR 1.09). The LB rate was higher with male factor infertility ejaculated sperm only (AOR 1.04). CONCLUSION(S) The ICSI and sperm source influence CIG and LB rates in male factor infertility cases.

A comparison of clomiphene citrate and human menopausal gonadotropin for use in conjunction with intrauterine insemination

OBJECTIVE To compare the outcome of superovulation using clomiphene citrate (CC) versus hMG in conjunction with IUI. DESIGN Sequentially assigned, observational study. Couples initially were assigned to receive either CC or hMG for three cycles. SETTING The Clinical Outpatient Department of the Dartmouth-Hitchcock Medical Center. PATIENT(S) Eighty-three infertile couples. INTERVENTION(S) IUI with hMG use. MAIN OUTCOME MEASURE(S) Conception rate, term pregnancy rate (PR), and pregnancy complications, such as spontaneous miscarriage and multiple gestation. RESULT(S) Of 83 couples who underwent at least one treatment cycle, 29 (35%) conceived during the study period. The relative rate of conception for hMG versus CC was 2.08 (95% confidence interval [CI], 0.93 to 4.68). The relative term PR was 2.10 (95% CI, 0.77 to 5.73) for hMG versus CC. There was no difference in the miscarriage rate for hMG versus CC. CONCLUSION(S) Both the conception rate and the term PR were higher using hMG, compared with CC, in combination with IUI, and showed a trend toward statistical significance.

Optimizing the number of cleavage stage embryos to transfer on day 3 in women 38 years of age and older : a Society for Assisted Reproductive Technology database study

OBJECTIVE To develop evidence-based recommendations for the optimum numbers of blastocyst stage embryos to transfer in women >or=38 years old. DESIGN Retrospective analysis of national Society for Assisted Reproductive Technology data from 2000 to 2004. SETTING National writing group. PATIENT(S) Five thousand five hundred sixty-nine day 5 and day 6 ETs in women >or=38 years of age undergoing their first assisted reproductive technology cycle. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Logistic regression was used to model the probability of a delivery, twins, and high-order multiples based on patient characteristics. RESULT(S) In 38- and 39-year-old women there was an increase in delivery rates up to transfer of two embryos. Beyond that, number transferred increased multiple rates but not delivery rates. Transfer of three embryos in 40-year-old women increased delivery but not multiple rate. For 41- to 42-year-olds delivery rate was level after transfer of three, but twin rate continued to increase. Multivariate analysis showed that age, embryo cryopreservation, and use of intracytoplasmic sperm injection influence delivery rate. Increasing numbers of oocytes retrieved showed a trend but was not an independent predictor. CONCLUSION(S) Optimal numbers of blastocyst stage embryos to transfer in first cycles for women 38 to 39 years old differ from those in women >or=40 years. Number transferred should be modified as determined by a model that includes availability of excess embryos to cryopreserve, use of intracytoplasmic sperm injection, and, possibly, number of oocytes retrieved.