ORIGINAL CONTRIBUTION Live-Birth Rates and Multiple-Birth Risk Using In Vitro Fertilization Laura A. Schieve, PhD Context To maximize birth rates, physicians who perform in vitro fertilization (IVF) Herbert B. Peterson, MD often transfer multiple embryos, but this increases the multiple-birth risk. Live-birth and multiple-birth rates may vary by patient age and embryo quality. One marker for Susan F. Meikle, MD embryo quality is cryopreservation of extra embryos (if embryos are set aside for cryo- Gary Jeng, PhD preservation, higher quality embryos may have been available for transfer). Isabella Danel, MD Objective To examine associations between the number of embryos transferred dur- ing IVF and live-birth and multiple-birth rates stratified by maternal age and whether Nancy M. Burnett, BS extra embryos were available (ie, extra embryos cryopreserved). Lynne S. Wilcox, MD Design and Setting Retrospective cohort of 300 US clinics reporting IVF transfer procedures to the Centers for Disease Control and Prevention in 1996. INCE THE GOAL OF IN VITRO FER- tilization (IVF) is pregnancy and, Subjects A total of 35 554 IVF transfer procedures. ultimately, live birth, clinical de- Main Outcome Measures Live-birth and multiple-birth rates (percentage of live cision making about IVF prac- births that were multiple). ticesS is heavily focused on maximizing Results A total number of 9873 live births were reported (multiple births from 1 preg- a woman’s chances of becoming preg- nancy were counted as 1 live birth). The number of embryos needed to achieve maximum nant. One common practice that aims live-birth rates varied by age and whether extra embryos were cryopreserved. Among wom- to increase the likelihood of pregnancy en 20 to 29 years and 30 to 34 years of age, maximum live-birth rates (43% and 36%, is to transfer multiple embryos (often respectively) were achieved when 2 embryos were transferred and extra embryos were more than 3) into the uterine cavity. This cryopreserved. Among women 35 years of age and older, live-birth rates were lower over- all and regardless of whether embryos were cryopreserved, live-birth rates increased if more treatment approach also presents an im- than 2 embryos were transferred. Multiple-birth rates varied by age and the number of portant drawback, however, because it embryos transferred, but not by whether embryos were cryopreserved. With 2 embryos increases the risk for multiple birth. Mul- transferred, multiple-birth rates were 22.7%, 19.7%, 11.6%, and 10.8% for women aged tiple-birth infants are at significant risk 20 to 29, 30 to 34, 35 to 39, and 40 to 44 years, respectively. Multiple-birth rates increased for a number of adverse outcomes in- as high as 45.7% for women aged 20 to 29 years and 39.8% for women aged 30 to 34 cluding preterm delivery, low birth years if 3 embryos were transferred. Among women aged 35 to 39 years, the multiple- weight, congenital malformations, fe- birth rate was 29.4% if 3 embryos were transferred. Among women 40 to 44 years of age, tal and infant death, and long-term mor- the multiple-birth rate was less than 25% even if 5 embryos were transferred. bidity and disability among survi- Conclusions Based on these data, the risk of multiple births from IVF varies by ma- vors.1-5 Twins are 5 times as likely, and ternal age and number of embryos transferred. Embryo quality was not related to mul- triplet and higher-order infants 13 times tiple birth risk but was associated with increased live-birth rates when fewer embryos were transferred. as likely, as singleton infants to die dur- ing the first year of life.2 JAMA. 1999;282:1832-1838 www.jama.com To curtail the multiple-birth risk, sev- eral countries have passed legislation remained outside the legal arena; how- tween various markers of embryo qual- that limits the number of embryos that ever, the American Society for Repro- ity and implantation, attention has fo- can be transferred to 3.6,7 Such a policy ductive Medicine has issued practice cused on whether such data can be 8 is not universally supported as it runs guidelines. The debate about embryo limits has increasingly focused on Author Affiliations: Division of Reproductive Health, counter to the expectation of au- National Center for Chronic Disease Prevention and tonomy in the patient-physician rela- whether to consider prognostic fac- Health Promotion, Centers for Disease Control and Pre- tors when setting guidelines, particu- vention, Atlanta, Ga. tionship. In the United States, the is- Corresponding Author and Reprints: Laura A. Schieve, sue of embryo transfer has thus far larly patient age, which varies in- PhD, Division of Reproductive Health, National Cen- versely with a woman’s chances for ter for Chronic Disease Prevention and Health Pro- achieving pregnancy.9,10 Additionally, motion, Centers for Disease Control and Prevention, See also p 1813 and Patient Page. Mailstop K-34, 4770 Buford Hwy NE, Atlanta, GA as studies demonstrate associations be- 30341 (e-mail: [email protected]). 1832 JAMA, November 17, 1999—Vol 282, No. 19 ©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 BIRTH RATES AND MULTIPLE-BIRTH RISK USING IVF translated into policy in the future. Al- ART data was 1996. In 1996, 300 US transfer, this number actually represents though current grading schemes for centers reported more than 60 000 ART 35 554 IVF transfer procedures. assessing embryo quality have limita- cycles to the CDC. Because some cen- tions, both embryo morphology grade ters did not report their data, despite the Definitions of IVF Outcomes and the ability to select embryos for federal mandate, this number does not We defined pregnancy as the presence transfer have been associated with in- represent every ART cycle performed in of 1 or more gestational sacs observed creased pregnancy and live-birth rates the United States; however, it is esti- on ultrasound (with or without the pres- in previous studies.11-17 An especially mated that data on more than 95% of all ence of a fetal heart). In rare instances provocative study that used population- cycles were reported. (,1%), the number of fetal sacs ob- based data from the United Kingdom Weselectedfresh,nondonorIVFcycles served on ultrasound was not recorded suggested that elective transfer of 2 for inclusion in the current analysis or was recorded as 0, but a pregnancy rather than 3 embryos reduced the mul- (N = 44 723). This refers to cycles in outcome was recorded (live birth, still- tiple-birth risk without affecting the which eggs were removed from a wom- birth, spontaneous abortion, therapeu- chance of live birth for any age group.11 an’s ovaries, combined with sperm, and tic abortion); these cycles were also To determine if this finding is sup- if fertilized, the resulting embryo(s) was coded as pregnancies. A total of 12 115 ported by the US IVF population, we replaced into the same woman’s uterus. pregnancies were reported. Since ART used a population-based dataset of IVF– This selection excludes cycles in which centers do not routinely treat patients assisted reproductive technology (ART) embryos derived from a woman serving beyond the first trimester, live births and cycles initiated in US clinics in 1996 to as an egg donor were transferred to the fetal losses later than the first trimester examine associations between em- patient (n = 5162); cycles in which em- were based on verbal or written reports bryo number and pregnancy, live- bryos derived from a patient were trans- from either the patient or her obstetric birth, and multiple-birth rates. The large ferred into another woman serving as a health care professional. ART centers of- sample afforded us an opportunity to gestational carrier or surrogate (n = 688); ten actively follow-up patients to ascer- more fully explore these associations by and cycles in which the embryos trans- tain pregnancy outcome. An outcome examining several important factors, in- ferred had been retrieved and fertilized (live birth, stillbirth, spontaneous abor- cluding patient age and availability of at an earlier date, frozen via cryopreser- tion, therapeutic abortion) was re- extra embryos for future ART cycles. vation, and thawed for use in the current corded for all but 457 (4%) of these preg- cycle (n = 9290). It also excludes cycles nancies. A total of 9873 live-birth METHODS in which embryos or oocytes were trans- deliveries were reported. We consid- Subjects ferred into a woman’s fallopian tubes ered each live-birth delivery as a single The Fertility Clinic Success Rate and rather than uterus (n = 4117), cycles in live birth; eg, a live-birth delivery of trip- Certification Act of 1992 requires that which embryos were transferred to both lets was counted as 1 live birth. each medical center performing IVF or the uterus and the fallopian tubes We classified a pregnancy as a mul- related ARTs report data for each ART (n = 619), and cycles in which both fresh tiple gestation if either 2 or more fetal cycle initiated to the Centers for Dis- and thawed embryos were transferred hearts were noted on an early ultra- ease Control and Prevention (CDC) an- (n = 125). Because these cycle types may sound, or 2 or more infants were born. nually for the purpose of reporting clinic- vary with respect to implantation and We defined multiple gestation based on specific pregnancy success rates.18 An pregnancy rates, and also with respect to the more stringent criterion of fetal ART cycle is considered to begin when the importance of various prognostic fac- hearts (rather than number of sacs only) a woman begins taking fertility drugs or tors, they were not combined.