Twin Research and Human Genetics Volume 19 Number 2 pp. 146–153 C The Author(s) 2016 doi:10.1017/thg.2016.4 Evidence for No Significant Impact of Mullerian¨ Anomalies on Reproductive Outcomes of Twin Pregnancy in Korean Women Sohyun Shim,1 Yoon-Mi Hur,2 Da Hee Kim,1 Seok Ju Seong,1 Mi-La Kim,1 andJoongSikShin1 1Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University, Seoul, South Korea 2Department of Education, Mokpo National University, Jeonnam, South Korea The present article aimed to evaluate the impact of congenital Mullerian¨ anomalies (MA) on twin pregnancy after 24 gestational weeks in Korean women. All records of twin pregnancies in a large maternity hospital in Korea between January 2005 and July 2013 were analyzed. Patients with monochorionic monoamniotic (MCMA) twins, non-Korean patients, patients with twins delivered prior to 24 gestational weeks, and patients with miscarriage of one fetus or intrauterine fetal death (IUFD) before 24 gestational weeks were excluded from data analysis. In total, 1,422 women with twin pregnancy were eligible for data analysis, including 17 (1.2%) who had a known congenital MA (septate uterus, bicornuate uterus, arcuate uterus, and unicornuate uterus). Except for the mode of conception, baseline demographics were similar between women with MA and those without MA. No significant differences were found in pregnancy outcomes of gestational age at delivery (p = .86), birth weight of smaller and larger twins (p = .54 and p = .65), and number of twins with birth weight <5th percentile for gestational age (p = .43).The rates of obstetrical complications such as pre-eclampsia, gestational diabetes mellitus (GDM), placenta previa, cerclage, IUFD, and postpartum hemorrhage were not significantly different between the two groups either. We concluded that the presence of congenital MA may not increase obstetrical risks in outcomes of pregnancy of twins delivered after 24 gestational weeks. Keywords: Mullerian¨ anomalies, twin, pregnancy outcome, obstetrical complications, uterine anomalies Congenital MA of the female reproductive tract com- A meta-analysis based on nine studies consisting of 3,805 prise a range of abnormalities caused by failure of any patients with MA (Chan et al., 2011) evaluated the effects part of the complex developmental series of the female of three types of MA (arcuate uteri, canalization defects, reproductive tracts, including failure of Mullerian¨ duct and unification defects) on reproductive outcomes. The development, elongation, fusion, canalization, and septal meta-analysis found that while all three types were sig- resorption. In MA, cervix, fallopian tubes, vagina, and nificantly related to fetal malformation at delivery, arcu- uterine anomalies are most common. The prevalence of ate uteri was specifically associated with increased rates MA in the general population is unknown, but several re- of second-trimester miscarriage, canalization defects, and cent studies indicated that MA occurs in approximately with reduced pregnancy rates, increased rates of first- 1–4% of reproductive-aged women, and 2–8% of infer- trimester miscarriage, and preterm birth, and unification tile women (Chan et al., 2011; Lin et al., 2002;Propst& defects as associated with increased rates of preterm deliv- Hill, 2000; Simon et al., 1991). Although some patients ery. However, all of the cases included in the meta-analysis have no significant clinical symptoms, congenital MA is associated with infertility and/or adverse pregnancy out- comes: approximately 5–10% of women with MA have RECEIVED 1 November 2015; ACCEPTED 13 January 2016. First been documented to have experienced recurrent early preg- published online 16 February 2016. nancy loss and up to 25% of women have experienced ADDRESS FOR CORRESPONDENCE: Joong Sik Shin or Mi-La Kim, late first- or second-trimester pregnancy loss, preterm Department of Obstetrics and Gynecology, CHA Gangnam labor, or fetal malpresentation following cesarean deliv- Medical Center, CHA University, 566, Nonhyeon-ro, Gangnam- ery (Lin et al., 2002;Propst&Hill,2000; Simon et al., gu, Seoul 135–081, South Korea. E-mail: [email protected]; 1991). [email protected] 146 Downloaded from https://www.cambridge.org/core. IP address: 170.106.202.226, on 24 Sep 2021 at 12:12:37, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/thg.2016.4 Mullerian¨ Anomalies in Twin Pregnancy were about singleton pregnancy, and none about twin phy (3-D ultrasonography), hysterosalpingography (HSG), pregnancies. Studies of the impact of MA on twin pregnan- hysteroscopy, laparoscopy, and magnetic resonance imag- cies were rarely done. To the best of our knowledge, only 14 ing (MRI). We included the corrected anomalies such as case reports (Ahmad et al., 2000; Arora et al., 2007;Aruh complete or partial resection of uterine septum using hys- et al., 2005;Brown,1999; Check et al., 1992; Cruceyra et al., teroscopy in the congenital MA group (AFS classifications, 2011; Doruk et al., 2013; Kekkonen et al., 1991;Nahra- 1988). Lynch & Toffle, 1997;Nahum,1997; Nanda et al., 2009; All twin pregnancies were managed following the uni- Nohara et al., 2003;Sugaya,2010; Weissman et al., 2006), form protocol of our clinic. During the first trimester, we and one comparative study (Fox et al., 2014) examined the confirmed the gestational age and chorionicity by TVS. If effect of MA on twin pregnancies to date. These studies also the patient visited our hospital after late second trimester suggested that the presence of MA in twin pregnancies sig- and chorionicity was unclear, we confirmed the chorionic- nificantly increased the risks for negative reproductive out- ity by pathological examination of the placenta. We adapted comes, including cerclage, preterm birth, and lower birth the definition of birth weight percentiles for gestational age weights and other obstetrical complications. presented in standard tables for twin pregnancies (Yarkoni Due to a recent rapid development of various assisted et al., 1987). reproductive technologies (ART), the rates of twin births Statistical analysis was performed using SPSS (version have been increased dramatically worldwide. For example, 12.0; SPSS, Chicago, IL, USA). Chi-square and Fisher’s exact the twinning rates rose from 18.9 in 1980 to 33.7 per thou- tests were used for analysis of categorical variables. Quanti- sand live births in 2013 in the United States (Martin et al., tative variables were compared by means of Mann–Whitney 2015). In South Korea, twin births increased from approxi- Utests.Ap value of <.05 was considered statistically mately 10 in 1981 to 18.8 per thousand births in 2007 (Hur significant. &Kwon,2005;Hur&Song,2009). As clinicians gener- ally recommend ART to women with congenital MA who experience infertility, the incidence of twin pregnancies in womenwithMAisexpectedtoincreaseinthefuture.How- Results ever, twin pregnancy itself is well known to have increased During the study period, a total of 1,478 twin deliveries risks in obstetrical complications, such as pre-eclampsia after gestational age of 24 weeks were recorded. Of these, 5 (Krotz et al., 2002), and negative outcomes of pregnancy cases were excluded as they had MCMA twins, 36 cases were such as preterm delivery (Kogan et al., 2002)andlowbirth patients who were non-Korean, and 13 cases were patients weight (Martin et al., 2015). Thus, it is important to inves- who had experienced miscarriage of one fetus or two fetuses tigatewhetherornotthepresenceofMAconfersadditional or IUFD at less than 24 gestational weeks. In total, 1,422 risks on twin pregnancies. In this study, we reviewed all patients were analyzed for the purpose of the present study. records of twin pregnancies in a large maternity hospital in Seventeen cases (1.2%) had a known congenital MA (septate Korea between January of 2005 and July of 2013 and com- uterus; n = 10), bicornuate uterus (n = 3), arcuate uterus pared obstetrical outcomes and complication rates in twin (n = 2), and unicornuate uterus (n = 2). All of the patients pregnancies with and without congenital MA. diagnosed with a septated uterus underwent hysteroscopic septotomy before the twin pregnancy. The baseline characteristics of the patients with MA and Materials and Methods those without MA are compared in Table 1.Onlymode In a review of maternity records, we used the following in- of conception was significantly different between patients clusion criteria for data analysis: (1) twins delivered after 24 with MA and those without MA (p < .001). However, a gestational weeks; (2) initially triplet pregnancy reduced to post-hoc analysis indicated that the rate of in vitro fer- twin pregnancy at the time of delivery due to miscarriage of tilization (IVF) was not significantly different between the one fetus, IUFD, or selective abortion before 24 gestational two groups (64.7% vs. 71.8%; p = 59), while two other cate- weeks; (3) one or two fetus IUFD after 24 gestational weeks. gories (natural or timed intercourse [TI], controlled ovarian We excluded the following cases from analysis: (1) patients hyperstimulation [COH] + TI; intrauterine insemination with MCMA twins because of the risk of cord entanglement [IUI] or COH + IUI) showed significant differences. and associated risk of IUFD or intended preterm delivery; Thepregnancyoutcomesbetweenthetwogroupsare (2) non-Korean patients; (3) patients with missed abortion shown in Table 2. There were no significant differences in of