An interdisciplinary lifestyle intervention improves clinically relevant fertility outcomes in obese infertile women - preliminary results

CLINICAL FEMALE INFERTILITY AND GYNECOLOGY O-253 Wednesday, October 21, 2015 11:15 AM AN INTERDISCIPLINARY LIFESTYLE INTERVENTION IMPROVES CLINICALLY RELEVANT FERTILITY OUTCOMES IN OBESE INFERTILE WOMEN - PRELIMINARY RESULTS. K. Duval,a,b M. Belan,a,b F. Jean-Denis,b J. Baillargeon.a,b aMedicine, Division of Endocrinology, Universite de Sherbrooke, Sherbrooke, QC, Canada; bCentre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada. OBJECTIVE: To assess the impact of a lifestyle intervention targeting obese infertile women on fertility outcomes. DESIGN: Randomized controlled trial. MATERIALS AND METHODS: Participants were followed for 18 months or until the end of pregnancy. They were randomized into the intervention (interdisciplinary lifestyle intervention without fertility treatments for the first six months) or control group (standard fertility treatments only). The lifestyle intervention consisted in individual’s encounters with a dietician and a kinesiologist every 6 weeks, and weekly group sessions (at least 12 different ones). Pregnancy was defined by a positive serum pregnancy test. A total of 105 women were randomized, 21 were excluded/withdrawn (13 intervention; 8 control), 29 are active in the study and 55 completed (24 intervention; 31 control). Only the results of participants who completed the study are presented. RESULTS: Mean age of participants was 30.2
4.7 yrs, BMI is 40.1
7.5 kg/m2, waist circumference is 118
16 cm, and 67% had polycystic ovary syndrome. As compared with the control group, women in the intervention group had significantly higher pregnancy rate (79.2% vs. 41.9%, p¼0.003) and spontaneous pregnancy rate (50.0% vs. 12.9% of all women, p¼0.003). There was no significant difference between groups for pregnancy following assisted reproductive technology (29% in both groups). Importantly, a tendency to a higher rate of life birth was observed in the intervention group (62.5 % vs. 38.7%, p¼0.08). At any time during the study, 42% of women in the intervention group and 36% in the control group lost R5% of their initial body weight (p¼NS). Furthermore, 50% of women in the intervention group and 36% in the control group lost R5 cm of their initial waist circumference (p¼NS). The median weight loss at time of pregnancy in women who delivered (n¼28) was -2.5% [-6.9 - -1.4%] (p¼0.0001) in the intervention group and -1.6% [-2.4 - +1.0] (p¼0.22) in controls (p¼0.05 between groups). CONCLUSIONS: These results demonstrate that even a modest weight loss following an interdisciplinary lifestyle intervention in obese infertile women could improve significantly their pregnancy rate, mainly the occurrence of a spontaneous pregnancy. They also suggest that the rate of living babies may also be improved. Such interdisciplinary lifestyle intervention may improve fertility by other factors than weight or waist loss alone. Supported by: Quebec Ministry of Health and Social Services, and Canadian Institutes of Health Research. O-254 Wednesday, October 21, 2015 11:30 AM CLOMID STAIR-STEP PROTOCOL MAY SHORTEN THE TIME TO OVULATION BUT NOT TO PREGNANCY: A RANDOMIZED CLINICAL TRIAL. L. B. Craig,a J. D. Peck,b D. Zhao,b K. R. Hansen.a aDept Ob/Gyn, Section Reproductive Endocrinology & Infertility, University of Oklahoma Health Sciences Center, Oklahoma City, OK; bDept of Biostatistics & Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK. OBJECTIVE: A novel dosing regimen for clomiphene citrate that involved increasing the dose (stair-step protocol) without inducing a period with progestin has been retrospectively described. The objective of this study was to prospectively compare length of time to ovulation and pregnancy with escalating doses of clomiphene administration in the traditional protocol versus the stair-step approach in women with ovulatory dysfunction. DESIGN: Unblinded, randomized clinical trial MATERIALS AND METHODS: Women ages 18-45 with anovulatory infertility were randomized in a 1:1 ratio at baseline ultrasound to two protocols for ovulation induction. The traditional protocol included clomiphene followed by progestin withdrawal if anovulatory before increasing the clomiphene dose. Under the stair-step protocol, clomiphene dose was increased cycle day 11-14 without a progestin withdrawal if no

FERTILITY & STERILITYÒ

follicle >12mm. Clomiphene dose started at 50mg and was increased up to 150mg per protocol. Primary outcome was time to ovulation. Secondary outcome was time to pregnancy. Outcomes were compared between the two treatment groups using the log-rank test and the proportions of ovulation/pregnancy versus time were plotted using the Kaplan-Meier method. The proportion of ovulation/pregnancy between the two treatment groups was analyzed with the chi-square test. RESULTS: A total of 120 patients (60 stair-step, 60 traditional) were randomized. The groups were similar in age, BMI, ethnicity, years of infertility, and smoking. There was no significant difference in proportion that ovulated between the stair-step and traditional groups (p¼0.77, 90.0% vs 88.3%). In addition, there was no significant difference in time to first ovulation between the two groups (p¼0.65). However, when comparisons were limited to the 49 patients (34 stair-step, 15 traditional) who did not ovulate at clomiphene 50mg, time to first ovulation was significantly decreased (p<0.001) among women on the stair-step protocol. The proportion of pregnancy was similar between stair-step and traditional groups (35.0% vs 35.0%). In addition, there was no significant difference in time to pregnancy between the two groups (p¼0.87), even when limiting analysis to the 49 subjects who did not ovulate at clomiphene 50mg (p¼ .56). CONCLUSIONS: In anovulatory patients resistant to clomiphene 50mg, the stair-step protocol shortened the time to ovulation, but did not shorten the time to pregnancy. Additional follow-up is necessary to determine if there are differences between treatment groups in the live-birth rate and the rate of congenital anomalies. Patient satisfaction is likely improved with the stairstep protocol by quicker determination of response to medication but this should be evaluated in future studies. This is the first study to prospectively evaluate the stair-step protocol. Supported by: Oklahoma Shared Clinical and Translational Resource Institute NIGMS U54 GM104938

O-255 Wednesday, October 21, 2015 11:45 AM PREDICTORS OF PREGNANCY AND LIVE-BIRTH IN COUPLES WITH UNEXPLAINED INFERTILITY FOLLOWING SUPEROVULATION-INTRAUTERINE INSEMINATION. K. R. Hansen,a A. W. He,b A. K. Styer,c S. Butts,d L. Engmann,e T. NICHD’s Reproductive Med Network.f aObstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK; bBiostatistics, Yale University School of Public Health, New Haven, CT; cMassachusetts General Hospital/Harvard Medical Sch, Boston, MA; dObstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA; eObstetrics and Gynecology, University of Connecticut Health Center, Farmington, CT; fEunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD. OBJECTIVE: To identify baseline characteristics of women associated with conception, clinical pregnancy, and live-birth following up to four cycles of superovulation (SO) with Letrozole, Clomiphene Citrate (CC), or gonadotropins plus intrauterine insemination (IUI) in couples with unexplained infertility. DESIGN: Secondary analyses of data from a prospective, randomized, multicenter clinical trial investigating pregnancy, live-birth, and multiple pregnancy rates following superovulation-intrauterine insemination treatments. MATERIALS AND METHODS: This secondary analysis included all 900 participants from The Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial. Briefly, this trial enrolled women age 18-40 with at least one patent fallopian tube and regular menses to undergo SO-IUI with Letrozole, CC or gonadotropins for up to four treatment cycles. Male partners were required to have a semen analysis with at least 5 million motile sperm in the ejaculate. Baseline demographic and biochemical parameters were evaluated as predictors of the outcomes of conception, pregnancy, and live-birth with bivariate and multivariable analyses. A p-value of < 0.05 was considered statistically significant. RESULTS: In a multivariable logistic regression analysis, age, waist circumference, income, duration of infertility, and a history of prior pregnancy loss were significantly associated with at least one pregnancy outcome. Age (OR¼0.93, CI¼0.90-0.97 per year), an income of > $50,000 USD (OR¼2.07, CI¼1.27-3.38), duration of infertility of >24 months (OR¼0.65, CI¼0.47-0.89), and history of a prior pregnancy loss (OR¼1.59, CI¼1.12-2.27) were significantly associated with the probability of live-birth. Other baseline demographic, biochemical, and lifestyle characteristics were not associated with outcomes. CONCLUSIONS: While age and duration of infertility were significant predictors of all pregnancy outcomes, most other baseline characteristics

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