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Conception rates and contraceptive use after bariatric surgery among women with infertility: Evidence from a prospective multicenter cohort study

Published:January 11, 2019DOI:https://doi.org/10.1016/j.soard.2018.12.026

      Highlights

      • Following bariatric surgery, women with infertility and nulliparity history have higher conception rates than those without history.
      • Following bariatric surgery, women with infertility and nulliparity history have higher risk of unprotected intercourse than those without history.

      Abstract

      Background

      Lack of prospective trials have resulted in a dearth of information regarding postbariatric surgery conception rates in women with a preoperative history of infertility.

      Objective

      To examine associations between preoperative history of infertility and postbariatric surgery conception.

      Setting

      A multicenter cohort study at 10 United States hospitals (2006–2009).

      Methods

      Participants completed a preoperative reproductive health questionnaire, with annual postoperative assessments for up to 7 years until January 2015. This report was restricted to women 18- to 44-years old with no history of menopause, hysterectomy, or hormone replacement therapy. The primary outcomes were postoperative (0 to <90 mo) conception rate, early conception rate (0 < 18 mo), and postoperative unprotected intercourse with a male partner while not trying to conceive.

      Results

      Of 740 eligible women, 650 (87.8%) provided required responses. Median interquartile range (IQR) preoperative age was 34 (30–39) years and follow-up was 6.5 (5.9–7.0) years. Nulliparous women with a preoperative history of infertility represented 8.0% (52/650) of the total cohort, 63.5% (33/52) of whom had never conceived. Compared with women without this history, these women had a higher postoperative conception rate (121.2 [95% confidence interval (CI), 102.3–143.5]/1000 versus 47.0 [95%CI, 34.2–62.9]/1000 woman-yr; P < .001), early conception rate (115.4 [95%CI, 96.1–138.5]/1000 versus 33.9 [95%CI, 23.6–47.1]/1,000 woman-yr; P < .01), and a higher risk of unprotected intercourse (ARR 1.48 [95% CI, 1.14-1.90], P = 0.003).

      Conclusion

      After bariatric surgery, preoperative history of infertility and nulliparity was associated higher conception rates and unprotected intercourse.

      Keywords

      Obesity has an inverse association with female reproductive potential that includes increased time to conception [
      • van der Steeg J.W.
      • Steures P.
      • Eijkemans M.J.
      • et al.
      Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women.
      ], increased lifetime odds of nulliparity [
      • Rich-Edwards J.W.
      • Goldman M.B.
      • Willett W.C.
      • et al.
      Adolescent body mass index and infertility caused by ovulatory disorder.
      ,
      • Polotsky A.J.
      • Hailpern S.M.
      • Skurnick J.H.
      • Lo J.C.
      • Sternfeld B.
      • Santoro N.
      Association of adolescent obesity and lifetime nulliparity–the Study of Women's Health Across the Nation (SWAN).
      ], and decreased efficacy of treatment options for infertility [
      • Luke B.
      • Brown M.B.
      • Stern J.E.
      • Missmer S.A.
      • Fujimoto V.Y.
      • Leach R.
      Female obesity adversely affects assisted reproductive technology (ART) pregnancy and live birth rates.
      ]. For patients with severe obesity (body mass index [BMI] ≥40 or 35 to <40 kg/m2 with serious co-morbid conditions), bariatric surgery is the most effective intervention for weight management [
      • Brolin R.E.
      Update: NIH consensus conference. Gastrointestinal surgery for severe obesity.
      ]. A recent position statement by the American Society for Metabolic and Bariatric Surgery, endorsed by the American College of Obstetricians and Gynecologists and the Obesity Society, notes improvements in fertility after bariatric surgery. However, evidence was primarily retrospective and based on case series studies [
      • Kominiarek M.A.
      • Jungheim E.S.
      • Hoeger K.M.
      • Rogers A.M.
      • Kahan S.
      • Kim J.J.
      American Society for Metabolic and Bariatric Surgery position statement on the impact of obesity and obesity treatment on fertility and fertility therapy Endorsed by the American College of Obstetricians and Gynecologists and the Obesity Society.
      ,
      • Legro R.S.
      Effects of obesity treatment on female reproduction: results do not match expectations.
      ]. The lack of prospective trials has resulted in a dearth of information regarding postoperative conception rates in women with a preoperative history of infertility.
      Data are similarly sparse regarding the overall postoperative reproductive practices of women with infertility [
      • Guelinckx I.
      • Devlieger R.
      • Vansant G.
      Reproductive outcome after bariatric surgery: a critical review.
      ]. We previously reported that 41.9% of women who had attempted to conceive before undergoing bariatric surgery had experienced infertility [
      • Gosman G.G.
      • King W.C.
      • Schrope B.
      • et al.
      Reproductive health of women electing bariatric surgery.
      ]. While most conceived and had at least 1 live birth before surgery, 38.6% of these women remained nulliparous [
      • Gosman G.G.
      • King W.C.
      • Schrope B.
      • et al.
      Reproductive health of women electing bariatric surgery.
      ]. This group of nulliparous women with infertility is of particular interest with regard to (1) postoperative fertility and (2) adherence to global recommendations to delay conception 12 to 18 months after bariatric surgery [
      • Mechanick J.I.
      • Youdim A.
      • Jones D.B.
      • et al.
      Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient–2013 update: cosponsored by American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery.
      ].
      The Longitudinal Assessment of Bariatric Surgery-2 study is a multicenter, prospective cohort study that has previously reported preoperative reproductive health status of women undergoing bariatric surgery [
      • Gosman G.G.
      • King W.C.
      • Schrope B.
      • et al.
      Reproductive health of women electing bariatric surgery.
      ] as well as postoperative reproductive-related practices and outcomes [
      • Menke M.N.
      • King W.C.
      • White G.E.
      • et al.
      Contraception and conception after bariatric surgery.
      ]. This report extends that work by examining postoperative conception rates and contraceptive practices among nulliparous women with a preoperative history of infertility.

      Methods

      Recruitment methodology and study design have previously been described [
      • Gosman G.G.
      • King W.C.
      • Schrope B.
      • et al.
      Reproductive health of women electing bariatric surgery.
      ,
      • Menke M.N.
      • King W.C.
      • White G.E.
      • et al.
      Contraception and conception after bariatric surgery.
      ,
      • Courcoulas A.P.
      • Christian N.J.
      • Belle S.H.
      • et al.
      Weight change and health outcomes at 3 years after bariatric surgery among individuals with severe obesity.
      ,
      • Belle S.H.
      • Berk P.D.
      • Courcoulas A.P.
      • et al.
      Safety and efficacy of bariatric surgery: Longitudinal Assessment of Bariatric Surgery.
      ,
      • Belle S.H.
      • Berk P.D.
      • Chapman W.H.
      • et al.
      Baseline characteristics of participants in the Longitudinal Assessment of Bariatric Surgery-2 (LABS-2) study.
      ]. Patients ≥18 years of age who underwent a first bariatric surgical procedure as part of routine care were recruited into Longitudinal Assessment of Bariatric Surgery-2, a multicenter prospective cohort study, at 10 hospitals within 6 clinical centers throughout the United States between 2005 and 2009.
      Before data collection, the institutional review boards at each center approved the protocol and all participants gave written informed consent to participate. Research assessments were conducted by Longitudinal Assessment of Bariatric Surgery–trained and –certified personnel independent of surgical care within 30 days before scheduled surgery dates and annually after surgery for up to 7 years or until January 2015. This report was restricted to women who were 18- to 44-years old and reported no history of surgical or natural menopause, hysterectomy, or hormone replacement therapy before their preoperative or first follow-up reproductive health assessment. Data collected after any of these criteria were met were excluded. Of 1931 female participants, 740 women met eligibility requirements, 650 (87.8%) of whom reported preoperative history of infertility and parity and provided postoperative conception information (Fig. 1).
      Fig. 1.
      Fig. 1Longitudinal Assessment of Bariatric Surgery-2 (LABS-2) Study Flow From Approached Patients to Analysis Sample.
      The primary exposure was preoperative history of infertility and nulliparity. Postoperative (0 <90 mo) conception rate was the primary outcome of interest. Conception rates stratified by postoperative interval and postoperative unprotected intercourse with a male partner while not trying to conceive were secondary outcomes. Use of fertility medications and pregnancy outcomes were exploratory outcomes.

      Assessments and definitions

      The preoperative Reproductive Health Questionnaire has been described [
      • Gosman G.G.
      • King W.C.
      • Schrope B.
      • et al.
      Reproductive health of women electing bariatric surgery.
      ]. A postoperative version was self-administered annually to obtain outcomes in the year before assessment [
      • Gourash W.F.
      • Ebel F.
      • Lancaster K.
      • et al.
      Longitudinal Assessment of Bariatric Surgery (LABS): retention strategy and results at 24 months.
      ]. In addition to the annual postoperative Reproductive Health Questionnaire, which assessed pregnancies in the past year, an annual Short Form (administered starting March 2010) and an Event and Complications Form (completed at the 4- or 5-yr postoperative assessment) assessed pregnancies “since surgery” to address missing data. If a postoperative pregnancy was reported on any form, participants were asked to complete a Pregnancy Questionnaire.
      Infertility was defined as having tried to conceive and a history of at least 12 months of regular, unprotected intercourse with a male partner that did not result in a pregnancy. Based on preoperative assessment, participants were categorized as (1) women who had never tried to conceive, (2) women with no history of infertility, (3) parous women with a history of infertility, and (4) nulliparous women with a history of infertility. Due to the sample size, frequency distribution of categories, and study aims, the first 3 categories were collapsed to evaluate “preoperative history of infertility and nulliparity” status [
      Practice Committee of the American Society for Reproductive M
      Diagnostic evaluation of the infertile female: a committee opinion.
      ].
      Conception rate was calculated as the number of postoperative pregnancies divided by follow-up time. Woman-years of follow-up were calculated using the time from date of surgery to the last date pregnancy status was known through the 7-year assessment window (90 mo postoperatively). In addition to the conception rate across follow-up (i.e., 0 to <90 mo), conception rates were calculated for (1) the early postoperative period during which pregnancy is not recommended (<18 mo), (2) the following 2 years, during which pregnancy is no longer contraindicated (18 to <42 mo), and (3) the remaining follow-up period (42–90 mo), using reported conception dates. If unavailable, conception date was estimated based on other data (due date, length of pregnancy, pregnancy outcome, and outcome date). The adjudication process for inconsistent data has been described previously [
      • Mechanick J.I.
      • Youdim A.
      • Jones D.B.
      • et al.
      Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient–2013 update: cosponsored by American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery.
      ]. Early conception (<18 mo; i.e., yes or no) was determined from conception dates. Pregnancy outcomes were reported as a live birth, still birth (baby lost after 20 wk or 5 mo), miscarriage (fetus lost before 20 wk or 5 mo), ectopic or tubal pregnancy, or abortion.
      Unprotected intercourse, defined as not “always” using contraception during sexual intercourse with a male, was determined at each assessment among women who were sexually active with a male, were not pregnant and were not trying to conceive [
      • Gosman G.G.
      • King W.C.
      • Schrope B.
      • et al.
      Reproductive health of women electing bariatric surgery.
      ,
      • Kim C.
      • Gebremariam A.
      • Iwashyna T.J.
      • Dalton V.K.
      • Lee J.M.
      Longitudinal influences of friends and parents upon unprotected vaginal intercourse in adolescents.
      ]. This classification scheme reflects the fact that the proportion of women reporting contraceptive use “most of the time” or “about half of the time'' was small, and that such practices increase risk of pregnancy. Thus, these categories were grouped with “rarely” and “never” using contraception as “unprotected intercourse.”
      Preoperative reproductive health characteristics. Participants self-reported characteristics of their menstrual cycle; past diagnosis of polycystic ovary syndrome (PCOS) by a healthcare professional; number of prior pregnancies (gravidity), live births and still births (parity); use of contraception for any reason in the past 12 months (yes or no); the importance of being able to become pregnant in the future (on a scale from 0–10); and the anticipated timeframe in which they would first try to become pregnant after surgery. Menstrual regularity was defined as a history of 10 to 12 menstrual periods lasting between 1 and 7 days on average, a usual cycle length of 21 to 35 days, and no spotting or bleeding at times other than menstrual period within the last 12 months. Importance of postoperative pregnancy was categorized as (1) important (rating of 8–10), (2) importance unclear (rating of 3–7), or (3) unimportant (rating of 0–2) or not planned (i.e., ‘never’) [
      • Gosman G.G.
      • King W.C.
      • Schrope B.
      • et al.
      Reproductive health of women electing bariatric surgery.
      ].
      Additional covariates. Age, race, ethnicity, education, medical insurance, marital status, and smoking were assessed using self-administered questionnaires. Race was considered missing for participants who did not report their race as at least 1 of the following: white or Caucasian, Black or black, Asian, American Indian or Alaska Native, or Native Hawaiian or Other Pacific Islander. When >1 type of insurance was reported, insurance type was coded according to the following hierarchy: government, private, other, or unknown. Medical history was determined using a combination of laboratory values, physical examination measures, participant-reported medication use, and co-morbid diagnoses from healthcare providers and medical records review [
      • Belle S.H.
      • Berk P.D.
      • Chapman W.H.
      • et al.
      Baseline characteristics of participants in the Longitudinal Assessment of Bariatric Surgery-2 (LABS-2) study.
      ,
      • Courcoulas A.P.
      • Christian N.J.
      • O'Rourke R.W.
      • et al.
      Preoperative factors and 3-year weight change in the Longitudinal Assessment of Bariatric Surgery (LABS) consortium.
      ]. Nonsurgical contraceptive risk was defined as any level 3 or 4 medical risk for contraceptive use as reported by the United States Medical Eligibility Criteria for Contraceptive Use [
      • Curtis K.M.
      • Tepper N.K.
      • Jatlaoui T.C.
      • et al.
      U.S. Medical Eligibility Criteria for Contraceptive Use, 2016.
      ].

      Statistical analysis

      Analyses were conducted using SAS versions 9.4 (SAS Institute, Cary, NC, USA) and in OpenEpi, Version 3 [
      • Dean A.G.
      • Sullivan K.M.
      • Soe M.M.
      OpenEpi: Open Source Epidemiologic Statistics for Public Health.
      ]. All reported P values were 2-sided; P values < .05 were considered statistically significant. Conception rates, with 95% confidence intervals (CI) constructed assuming the Poisson distribution, are reported by preoperative history of infertility and nulliparity. The mid-P exact test was used to determine whether conception rates differed by group.
      A Poisson mixed model with robust error variance with a person-level random intercept was used to test and estimate associations between preoperative history of infertility and nulliparity with early conception with a person-level random intercept. Analysis was repeated controlling for the following potential preoperative confounders: age [
      • Menke M.N.
      • King W.C.
      • White G.E.
      • et al.
      Contraception and conception after bariatric surgery.
      ,
      American College of Obstetricians and Gynecologists Committee on Gynecologic Practice and Practice Committee
      Female age-related fertility decline. Committee Opinion No. 589.
      ], race [
      • Humphries L.A.
      • Chang O.
      • Humm K.
      • Sakkas D.
      • Hacker M.R.
      Influence of race and ethnicity on in vitro fertilization outcomes: systematic review.
      ], ethnicity [
      • Maalouf W.
      • Maalouf W.
      • Campbell B.
      • Jayaprakasan K.
      Effect of ethnicity on live birth rates after in vitro fertilisation/intracytoplasmic sperm injection treatment: analysis of UK national database.
      ], education [
      • Swift B.E.
      • Liu K.E.
      The effect of age, ethnicity, and level of education on fertility awareness and duration of infertility.
      ], marital status [
      • Menke M.N.
      • King W.C.
      • White G.E.
      • et al.
      Contraception and conception after bariatric surgery.
      ], BMI [
      Practice Committee of the American Society for Reproductive M
      Obesity and reproduction: a committee opinion.
      ], current or recent smoker [
      Practice Committee of the American Society for Reproductive Medicine
      Smoking and infertility: a committee opinion.
      ], menstrual regularity, any contraceptive use, history of PCOS [
      Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.
      ], and surgical procedure.
      Poisson mixed models with robust error variance were used to test and estimate the association between preoperative history of infertility and nulliparity and risk of postoperative unprotected intercourse with a person-level random intercept, controlling for site, preoperative education, and preoperative BMI, which were associated with missing follow-up data, as fixed effects. An interaction with time was considered and retained if significant. Analysis was repeated controlling for the following potential confounders: preoperative age [
      • Mosher W.
      • Jones J.
      • Abma J.
      Nonuse of contraception among women at risk of unintended pregnancy in the United States.
      ], race [
      • Menke M.N.
      • King W.C.
      • White G.E.
      • et al.
      Contraception and conception after bariatric surgery.
      ,
      • Jackson A.V.
      • Karasek D.
      • Dehlendorf C.
      • Foster D.G.
      Racial and ethnic differences in women's preferences for features of contraceptive methods.
      ], ethnicity [
      • Jackson A.V.
      • Karasek D.
      • Dehlendorf C.
      • Foster D.G.
      Racial and ethnic differences in women's preferences for features of contraceptive methods.
      ], education [
      • Mosher W.
      • Jones J.
      • Abma J.
      Nonuse of contraception among women at risk of unintended pregnancy in the United States.
      ], BMI, any contraceptive use [
      • Menke M.N.
      • King W.C.
      • White G.E.
      • et al.
      Contraception and conception after bariatric surgery.
      ], and history of PCOS [
      • Joham A.E.
      • Boyle J.A.
      • Ranasinha S.
      • Zoungas S.
      • Teede H.J.
      Contraception use and pregnancy outcomes in women with polycystic ovary syndrome: data from the Australian Longitudinal Study on Women's Health.
      ]; surgical procedure; and postoperative marital status [
      • Mosher W.
      • Jones J.
      • Abma J.
      Nonuse of contraception among women at risk of unintended pregnancy in the United States.
      ], medical insurance [
      • Mosher W.
      • Jones J.
      • Abma J.
      Nonuse of contraception among women at risk of unintended pregnancy in the United States.
      ], menstrual regularity [
      • Yao X.
      • Stewart E.A.
      • Laughlin-Tommaso S.K.
      • Heien H.C.
      • Borah B.J.
      Medical therapies for heavy menstrual bleeding in women with uterine fibroids: a retrospective analysis of a large commercially insured population in the USA.
      ], and nonsurgical contraceptive risk [
      • Menke M.N.
      • King W.C.
      • White G.E.
      • et al.
      Contraception and conception after bariatric surgery.
      ,
      • Curtis K.M.
      • Tepper N.K.
      • Jatlaoui T.C.
      • et al.
      U.S. Medical Eligibility Criteria for Contraceptive Use, 2016.
      ]. Unadjusted relative risk (RR) and adjusted relative risks (ARR), 95%CI and P values are reported.
      Exploratory analysis. To explore whether importance of postoperative pregnancy might mediate the association between a preoperative history of infertility and nulliparity with early postoperative conception, it was added to the multivariate model. In addition, to explore whether risk of early conception and unprotected intercourse, respectively, differed by the more refined preoperative history of infertility categorizations, the models describe above were repeated comparing, “history of infertility and nulliparity,” “parous with a history of infertility,” and “never tried to conceive,” versus “no history of infertility.” Descriptive statistics were used to report fertility medication use and pregnancy outcomes by preoperative history of infertility and nulliparity.

      Results

      This report includes data provided by 650 women for whom a medical history of infertility or parity was reported. The median follow-up time was 6.5 (5.9–7.0) years. The median interquartile range (IQR) preoperative age was 34 (30–39) years. At preoperative assessment, 53.8% (350/650) reported an interval in their past medical history when they had attempted to conceive, 49.1% (172/350) of these women reported a history of infertility. Most women with a history of infertility subsequently conceived and delivered a live birth before bariatric surgery (69.8%, 120/172); 30.2% (52/172) remained nulliparous. Women with a preoperative history of infertility and nulliparity represented 8.0% (52/650) of the entire sample and 14.9% (52/350) of women who had ever tried to conceive. An additional 18.5% (120/650) of the sample reported a history of both infertility and delivery (i.e., parous with a history of infertility) before bariatric surgery, while 27.2% (177/650) had no history of infertility and 45.5% (296/650) reported never having tried to conceive. Five women (1.0%) reported a history of a live or still birth but did not disclose whether they had a history of infertility.
      Demographic characteristics of women by preoperative history of infertility and nulliparity are reported in Table 1. Nulliparous women with a preoperative history of infertility were not significantly different compared with those without this history with respect to age (P = .19), ethnicity (P = .08), being married or living as married (P = .69), and smoking status (P = .37). However, lower proportions were white (P < .001) and had a college degree (P = .047).
      Table 1Demographic characteristics of women aged 18–44 years before bariatric surgery, stratified by infertility status.
      Total

      (N = 650
      Data are reported as n (%) unless otherwise indicated. Denominators shift between variables due to missing data.
      )
      No history of infertility and/or parous

      (N = 598
      Data are reported as n (%) unless otherwise indicated. Denominators shift between variables due to missing data.
      )
      Nulliparous with a history of infertility

      (N = 52
      Data are reported as n (%) unless otherwise indicated. Denominators shift between variables due to missing data.
      )
      n%n%n%P
      Age, yr.19
       median (25th, 75th percentile)34(30, 39)35(30, 39)32(30, 37)
      White race
      Nonwhite races were combined due to the low frequency of each.
      <.001
       Missing770
       No10316.98615.61732.7
       Yes54083.150585.43567.3
      Hispanic ethnicity.08
       No60292.6
       Yes487.4416.9713.5
      Education.047
       Missing550
       High school or less11117.210117.01019.2
       Some college28444.025442.83057.7
       College degree or higher25038.823840.11223.1
      Married or living as married.69
       Missing660
       No27743.025643.22140.4
       Yes36757.033656.83159.6
      Current or recent smoker.37
       Missing110
       No52981.548981.94076.9
       Yes12018.510818.11223.1
      low asterisk Data are reported as n (%) unless otherwise indicated. Denominators shift between variables due to missing data.
      Nonwhite races were combined due to the low frequency of each.
      Clinical characteristics by preoperative history of infertility and nulliparity are provided in Table 2. Preoperative BMI (P = .37) did not differ by this history. Nulliparous women with a preoperative history of infertility, compared with those without this history, were less likely to have a regular menstrual cycle (P = .02) and to have used contraception in the year before the preoperative assessment (P < .001), and more likely to have a history of PCOS (P < .001). They also had fewer prior pregnancies (P < .001; 63.5% had never conceived), and by definition, no history of live birth. Importance or plan for postoperative pregnancy did vary by this history (P < .001); over half (56.9%) of nulliparous women with a history of infertility reported postoperative pregnancy plans as ‘important’. Surgical procedure did not differ among nulliparous women with a preoperative history of infertility compared with those without this history (P = .60).
      Table 2Clinical characteristics of women aged 18–44 years before bariatric surgery, stratified by infertility status.
      Total

      (N = 650
      Data are reported as N (%) unless otherwise indicated. Denominators shift between variables due to missing data.
      )
      No history of infertility and/or parous

      (N = 598
      Data are reported as N (%) unless otherwise indicated. Denominators shift between variables due to missing data.
      )
      Nulliparous with a history of infertility

      (N = 52
      Data are reported as N (%) unless otherwise indicated. Denominators shift between variables due to missing data.
      )
      n%
      Data are reported as N (%) unless otherwise indicated. Denominators shift between variables due to missing data.
      n%
      Data are reported as N (%) unless otherwise indicated. Denominators shift between variables due to missing data.
      n%
      Data are reported as N (%) unless otherwise indicated. Denominators shift between variables due to missing data.
      P
      Body mass index
      Calculated as weight in kilograms divided by height in meters squared.
      ,
       median (25th, 75th percentile)46.3(42.5, 51.4)46.3(42.4, 51.4)46.9(43.7, 52.7).37
      Menstrual regularity2.02
       Missing15914316
       No23948.721547.42466.7
       Yes25251.324052.71233.3
      History of PCOS13620.910918.22751.9<.001
      Gravidity<.001
       Missing880
       None20832.417529.73363.5
       111618.110818.3815.4
       212219.011719.859.6
       39615.09415.923.8
       4507.8488.123.8
       5274.2254.223.8
       ≥6233.6233.90.0
      History of live birth<.001
       Missing880
       No25439.620234.252100
       Yes38860.438865.800
      History of still birth00.0.47
       Missing880
       No63699.158699.52100
       Yes60.961.900
      Any contraceptive use in prior year932855.4.04
       Missing660
       No29545.826444.63159.6
       Yes34954.232855.42140.4
      Importance or plan for postsurgical pregnancy
       Missing981<.001
       Important19129.816227.52956.9
       Importance unclear9815.38414.21427.5
       Unimportant or not planned35254.934458.3815.7
      Surgical procedure.60
       Roux-en-Y gastric bypass47272.643973.43363.5
       Laparoscopic adjustable band15423.713823.11630.8
       Other
      Sleeve gastrectomy (n = 10), banded Roux-en-Y gastric bypass (n = 6), and biliopancreatic diversion with duodenal switch (n = 8) were combined due to the low frequency of each.
      243.7213.535.8
      PCOS = polycystic ovary syndrome.
      low asterisk Data are reported as N (%) unless otherwise indicated. Denominators shift between variables due to missing data.
      Calculated as weight in kilograms divided by height in meters squared.
      Sleeve gastrectomy (n = 10), banded Roux-en-Y gastric bypass (n = 6), and biliopancreatic diversion with duodenal switch (n = 8) were combined due to the low frequency of each.
      Conception rates stratified by preoperative history of infertility and nulliparity are reported in Table 3. Women with a preoperative history of infertility and nulliparity had a higher conception rate (121.2 [95%CI, 102.3–143.5] per 1000 woman-yr) versus those with no such history (47.0 [95%CI, 34.2–62.9] per 1000 woman-yr) across follow-up (P < .001). Early (<18 mo) and delayed (18 to <42 mo) conception rates were also higher in women with a preoperative history of infertility and nulliparity versus woman without this history, whereas CIs overlapped for late (42 to <90 mo) conception rates (Table 3).
      Table 3Conception rates after bariatric surgery among women aged 18–44 years by infertility status.
      Conception rate (95% CI) per 1000 person-yr
      Preoperative history nulliparity and infertility
      No (N = 598)Yes (N = 52)P
      Mid-P exact test.
      Time since surgery
      Overall: 0 to <90 mo
      Median follow-up time is 6.5 (5.9, 7.0) yr.
      47.0 (34.2–62.9)121.2 (102.3–143.5)<.001
      Early: 0 to <18 mo33.9 (23.6–47.1)115.4 (96.1–138.5)<.01
      Delayed: 18 to <42 mo53.1 (39.4–70.1)147.3 (124.3–173.8)<.001
      Late: 42 to <90 mo42.4 (30.3–57.7)74.8 (58.7–95.0).06
      low asterisk Mid-P exact test.
      Median follow-up time is 6.5 (5.9, 7.0) yr.
      Among 52 women with a preoperative history of infertility and nulliparity, 33 postoperative pregnancies were reported by 22 women. Postoperative use of fertility medications was reported by 30% (6/20; 2 missing) of these women, although only 10% (2/20) reported use at the time(s) of conception. Two thirds (65.6%; 21/32) of pregnancies resulted in live births, 25.0% (8/32) in miscarriages, 6.3% (2/32) in abortions, and 3.1% (1/32) ectopic pregnancies. The outcome of 1 pregnancy was not reported (Table 4).
      Table 4Pregnancy outcomes after bariatric surgery among women aged 18–44 years by infertility status (N = 650).
      Birth outcomen (%)
      Live birthStill birthEctopicMiscarriageAbortion
      No history of infertility and/or parous (n = 598)
      Among 598 women without infertility without live birth, the outcomes of 127 of 166 pregnancies (76.5%) were reported.
      Outcome known (127 pregnancies)87 (68.5)2 (1.6)1 (.8)29 (22.8)8 (6.3)
      Potential values
      The range of potential values for each type of outcome was determined by assigning none to all of the unknown outcomes to each type.
      (166 pregnancies)
      87–1262-411–4029–688–47
      (52.4–75.9)(1.2–24.7)(.6–24.1)(17.5–41.0)(4.8–28.3)
      Nulliparous with a history of infertility (N = 52)
      Among 52 women with infertility without live birth, the outcomes of 32 of 33 pregnancies (97.0%) were reported.
      Outcome known (32 pregnancies)21 (65.6)01 (3.1)8 (25.0)2 (6.3)
      Potential values
      Among 52 women with infertility without live birth, the outcomes of 32 of 33 pregnancies (97.0%) were reported.
      (33 pregnancies)
      21–22 (63.6–66.6)0–1 (0–3.0)1–2 (3.0–6.1)8–9 (24.2–27.3)2–3 (6.1–9.1)
      low asterisk Among 598 women without infertility without live birth, the outcomes of 127 of 166 pregnancies (76.5%) were reported.
      The range of potential values for each type of outcome was determined by assigning none to all of the unknown outcomes to each type.
      Among 52 women with infertility without live birth, the outcomes of 32 of 33 pregnancies (97.0%) were reported.
      Women with a preoperative history of infertility and nulliparity versus no such history had a higher risk of early conception (unadjusted RR 2.99 [95%CI, 1.28–6.99], P = .01). However, the association was slightly attenuated and no longer reached the threshold for statistical significance after adjustment for confounders (ARR 2.53 [95% CI, 0.97–6.59], P = 0.06), likely reflecting low statistical power. When importance of post-surgical pregnancy was added to the multivariate model as an exploratory analysis, the association between preoperative nulliparity with a history of infertility and early conception became weaker still (ARR 1.34 [95% CI, 0.47–3.79], P = 0.58), suggesting it may mediate the association.
      In a second exploratory analysis we utilized the more refined preoperative history of infertility categorizations. When compared to those with no preoperative history of infertility, a history of infertility and nulliparity was significantly associated with a greater risk of early conception, even with adjustment for confounders (RR 4.74 [95% CI, 1.73–12.96]. P = 0.002; ARR 3.85 [95% CI, 1.25–11.88] P = 0.02). RR estimates associated with parous with a history of infertility (RR 2.62 [95% CI, 1.05–6.52], P = 0.04; ARR 2.24 [95% CI 0.78–6.46], P = 0.13) and never tried to conceive (RR 1.72 [95% CI, 0.68–4.38], P = 0.25; ARR 1.53 [95% CI, 0.54–4.29], P = 0.42) versus no preoperative history of infertility were also > than 1, but were not significant.
      With regard to contraception, nulliparous women with a preoperative history of infertility versus no such history had an increased risk of unprotected intercourse while not trying to conceive (RR 1.58 [95%CI, 1.24–2.01], P < .001); this association did not differ over time. After adjustment for potential confounders, this association was slightly attenuated (ARR 1.48 [95% CI, 1.14–1.90], P = 0.003). Further insight was gained with the use of more refined preoperative history of infertility categorizations. Specifically, compared with those with no preoperative history of infertility, both nulliparous women with a preoperative history of infertility (RR 1.74 [95%CI, 1.33–2.27]; ARR 1.59 [95%CI, 1.21–2.08]) and parous women with a preoperative history of infertility (RR 1.39 [95%CI, 1.11–1.75]; ARR 1.30 [95%CI, 1.04–1.64]) were at increased risk of unprotected intercourse; risk did not differ for women who had never tried to conceive (RR 1.05 [95%CI, .83–1.32]; ARR 1.01 [95%CI, .80–1.27]).

      Discussion

      Throughout the postoperative follow-up period, nulliparous women with a history of infertility, compared with women without this history, had a 48% higher risk for unprotected intercourse while not trying to conceive. Our exploratory analysis suggests that compared with those with no history of infertility, parous women with a history of infertility were also at increased risk. These findings may indicate a perceived inability to conceive among women with a preoperative history of infertility and need for counseling regarding the potential effects of bariatric surgery on fertility, which is currently considered adjunctive therapy for infertility [
      Practice Committee of the American Society for Reproductive M
      Obesity and reproduction: a committee opinion.
      ]. Although lifestyle intervention is often recommended as first-line therapy, recent literature suggests that, compared with immediate infertility treatment, weight loss through a structured lifestyle program does not provide benefit in birth outcomes [
      • Mutsaerts M.A.
      • van Oers A.M.
      • Groen H.
      • et al.
      Randomized trial of a lifestyle program in obese infertile women.
      ]. We were unable to compare pregnancy outcomes by preoperative history of infertility and nulliparity due to missing outcome data among those without this history. However, the proportion of miscarriages (25%) in women with preoperative history of infertility and nulliparity is comparable to miscarriage rates (15%–25%) in the general population [
      Practice Committee of the American Society for Reproductive Medicine
      Evaluation and treatment of recurrent pregnancy loss: a committee opinion.
      ].
      We found that postoperative conception rates were approximately 2.5-fold higher in nulliparous women with a preoperative history of infertility compared with those without this history. This increase includes the early, postoperative time frame (<18 mo) when conception is contraindicated. This is consistent with our previous research [
      • Menke M.N.
      • King W.C.
      • White G.E.
      • et al.
      Contraception and conception after bariatric surgery.
      ] showing that postoperative contraceptive use and conception rates among women who undergo bariatric surgery do not reflect recommendations for an 18-month delay in conception after bariatric surgery [
      • Mechanick J.I.
      • Youdim A.
      • Jones D.B.
      • et al.
      Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient–2013 update: cosponsored by American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery.
      ]. Interestingly, delayed (18 to <42 mo) conception rates were also increased in this group suggesting that a preoperative history of infertility and nulliparity may not adversely affect fertility status during the timeframe in which postoperative conception is no longer contraindicated.
      Limitations of this study are primarily related to statistical power, a result of the small number with a history of infertility and nulliparity. Although not as strict as the standard definition of primary infertility (i.e., infertility with no prior history of conception), we anticipated that inclusion of women with a history of infertility who previously conceived, but did not report a history of still or live birth, would capture the population most likely to engage in unprotected postoperative intercourse, as well as those most interested in early and overall postoperative conception, while increasing our statistical power. Still, we had low statistical power to evaluate whether preoperative parity with history of infertility was independently related to risk of early conception. Additionally, small sample sizes did not allow for comparisons of fertility medication use. Despite these limitations, this study's standardized assessment of a large, multicenter cohort of geographically diverse participants over 7 years, distinguish it from previous case-series studies [
      • Kominiarek M.A.
      • Jungheim E.S.
      • Hoeger K.M.
      • Rogers A.M.
      • Kahan S.
      • Kim J.J.
      American Society for Metabolic and Bariatric Surgery position statement on the impact of obesity and obesity treatment on fertility and fertility therapy Endorsed by the American College of Obstetricians and Gynecologists and the Obesity Society.
      ].

      Conclusions

      Nulliparous women with a preoperative history of infertility were at increased risk for unprotected intercourse without intent to conceive across follow-up and had higher early postoperative conception rates compared with women without this history, indicating that effective contraceptive counseling is particularly lacking in this subgroup. Counseling of these women could benefit from recognition that conception rates were also higher in the delayed timeframe. Given these findings, clarification of the role of bariatric surgery for infertility warrants further investigation.

      Disclosures

      A.C. has received research grants from Covidien, Ethicon, Nutrisystem, and PCORI, and consultant fees from Apollo Endosurgery. D.F. has had an advisor role with Pacira Pharmaceuticals, has provided expert testimony for Surgical Consulting LLC, and has received travel expenses from Patient Centered outcomes research institute. W.P. has received research grants from J & J, Janssen Pharmaceuticals. B.W. has received consultant fees from Enteromedics. A.P. is a consultant and speaker for Medtronic and Ethicon and WL Gore and Associates. The other authors did not report any potential conflicts of interest.

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