Middle East Fertility Society Journal (2013) xxx, xxx–xxx Middle East Fertility Society Middle East Fertility Society Journal www.mefsjournal.org www.sciencedirect.com ORIGINAL ARTICLE Risk of first trimester spontaneous miscarriage among singleton gestations following ICSI and its relation to underlying cause of infertility Wessam Magdi Abuelghar a,*, Osama Saleh Elkady a, Tarek Fathi. Tamara a, Mona Hassan Khalil b a Obstetrics and Gynaecology Department, Ain-shams University, Cairo, Egypt b Obstetrics and Gynaecology Department, El Khazendara MOH Hospital, Cairo, Egypt Received 16 April 2013; accepted 12 June 2013 KEYWORDS Abstract Study objective: To assess the association between the first trimester miscarriage rates Miscarriage; among women undergoing intracytoplasmic sperm injection (ICSI) and underlying etiology of ICSI; infertility. Infertility Design: Prospective cohort study. Setting: Ain Shams University maternity hospital. Materials and methods: The study included women who became pregnant with singleton preg- nancy following ICSI as a treatment for different causes of infertility. Women were followed up throughout the first trimester of pregnancy up to 12 weeks’ gestation (10 weeks after the day of embryo transfer). Main outcome measure: First trimester miscarriage rate. Results: Two hundred and thirty four pregnant young women were included in the study, 164 (70.9%) women miscarried. The causes of infertility among these women were as follows: 41 (25%) mild male factor infertility, 40 (24.4%) severe male factor infertility, 45 (27.44%) tubal fac- tor, 7 (4.27%) polycystic ovarian syndrome, 3 (1.83%) endometriosis, 20 (12.19%) unexplained and Abbreviations: BMI, body mass index; CI, confidence interval; E2, estradiol; ET, embryo transfer; FSH, follicle stimulating hormone; GnRH, gonadotropin-releasing hormone; hCG, human chorionic gonadotropin; ICSI, intracytoplasmic sperm injection; IVF, in vitro fertilization; LH, luteinizing hormone; LMP, last menstrual period; OR, odds ratio; SD, standard deviation * Corresponding author. Tel.: +20 1227460679. E-mail address: [email protected] (W.M. Abuelghar). Peer review under responsibility of Middle East Fertility Society. Production and hosting by Elsevier 1110-5690 Ó 2013 Production and hosting by Elsevier B.V. on behalf of Middle East Fertility Society. http://dx.doi.org/10.1016/j.mefs.2013.06.005 Please cite this article in press as: Abuelghar WM et al. Risk of first trimester spontaneous miscarriage among singleton gestations following ICSI and its relation to underlying cause of infertility, Middle East Fertil Soc J (2013), http://dx.doi.org/10.1016/j.mefs.2013.06.005 2 W.M. Abuelghar et al. 8 (4.87%) multifactorial. Stepwise logistic multi-regression analysis showed that both maternal age (>31 years) and tubal block were the most sensitive discriminators for the prediction of first trimes- ter spontaneous miscarriage among the study population (P < 0.01). Major conclusions: First trimester spontaneous miscarriage rates among pregnant women with singleton pregnancy following ICSI were related to maternal age >31 years and/or the presence of tubal block. Ó 2013 Production and hosting by Elsevier B.V. on behalf of Middle East Fertility Society. 1. Introduction According to the underlying cause of infertility, all women were categorized. Tubal factor diagnosis was confirmed by Miscarriage is the most frequent complication of pregnancy hysterosalpingography, and or pelvic laparoscopy and male and it is assumed that fetal viability is only achieved in 30% factor infertility was diagnosed by semen criteria meeting the of all pregnancies, 50% of which are lost prior to the first World Health Organization (1999) criteria (7,8). Mild oligozo- 6 missed period (1). Gestational age, maternal age, previous his- ospermia (1–19 · 10 sperm/ml) was considered as mild male 6 tory of miscarriage and smoking are the major risk factors for factor and severe oligozoospermia (<10 sperm/ml) was con- miscarriage (2). sidered as severe male factor. Polycystic ovary syndrome ICSI (intracytoplasmic sperm injection) is a microscopic (PCOS) was diagnosed according to Rotterdam criteria [2 maneuver used to facilitate fertilization by injecting a single out of 3 from the following: 1. Oligo- or anovulation, 2. Clin- sperm directly into the oocyte (3). Achievement of pregnancy ical and/or biochemical signs of hyperandrogenism, 3. Polycys- in ICSI cycles is a real confrontation to physicians as it is tic ovaries by transvaginal sonography (presence of 12 or more the last and most advanced track in the management of infer- follicles in each ovary measuring 2–9 mm in diameter, and/or tility till now. Although there was a great advancement in the increased ovarian volume >10 ml)] (9). Endometriosis was success rate in the last few years, a range between 30% and diagnosed by either the presence of endometrioma(s) by trans- 40% is never pleasing to both physicians and patients (4). vaginal ultrasound and/or the laparoscopic criteria of the Moreover, miscarriage meaningfully reduces the initial success American Fertility Society classification (10). Infertility was and capability of ICSI treatment, increasing the psychological diagnosed as unexplained if all of the following were within grievance of patients (5). Since chromosomal aberrations (fre- normal: mid-luteal serum progesterone level for the detection quently aneuploidy) have been accounted for 50–75% of mis- of ovulation, hysterosalpingography and/or laparoscopy for carriages during the first trimester of gestation, one measurable tubal patency and semen analysis (11). According to our local outcome to authenticate the safety of ICSI can be the rate of institutional protocol, long mid-luteal protocol was applied in miscarriage among ICSI pregnancies (6). The differences in all cycles. Down regulation was done using gonadotropin- Ò miscarriage rates in ICSI are not completely understood and releasing hormone (GnRH) agonist (Decapeptyl 0.1 mg, Fer- may emanate from predisposing factors that are more preva- ring, Switzerland) starting from day 17 of the previous cycle. lent in patients suffering from infertility (5). The aim of the GnRH agonist was taken as a single subcutaneous injection till current work was to assess the association between underlying day two of the treatment cycle when the dose was reduced to etiology of infertility and first trimester miscarriage rates half the dose till the day of human chorionic gonadotropin among women who underwent intracytoplasmic sperm injec- (hCG) injection. tion (ICSI). The induction of ovulation was done using gonadotropin hormones, 75 IU FSH, 75 IU LH (MerionalÒ,IBSA,Switzer- land), starting from cycle day two calculated according to age, 2. Materials and methods weight and antral follicle count, then the dose was fashioned according to each patient’s response as monitored by follicul- The current prospective study was conducted at the assisted ometry. Embryo transfer had been carried for all cases on the reproduction unit of Ain Shams University maternity hospital 3rd day post ovum pick up. After embryo-transfer, 100 mg from January 2009 to December 2011 and included young intramuscular daily progesterone was given to all women for pregnant women with singleton pregnancy, proved by trans- 8 weeks as a luteal phase support (ProntogestÒ,EIPICOfor vaginal ultrasound, following ICSI as a treatment for different Marcyrl Pharmaceutical Industries, Egypt). Quantitative hCG causes of infertility. Women were followed up throughout the was done 2 weeks later to diagnose chemical pregnancy, and first trimester of pregnancy up to 12 weeks’ gestation (10 weeks once more after 48 h to ensure the doubling pattern, then trans- after the day of embryo transfer). All couples were thoroughly vaginal ultrasound (TVUS) was performed 2 weeks after posi- informed about the treatment procedures, and written in- tive pregnancy tests to confirm the presence of gestational sac formed consent was obtained from all women. The treatment with fetal echo and pulsation and to exclude ectopic pregnancy. protocols were approved by the Ethics Committee of Ain Once more TVUS was performed at 12 weeks gestation to deter- Shams University maternity Hospital, Cairo, Egypt in accor- mine the main outcome measure, early pregnancy failure. dance with local institutional research governance require- The diagnosis of early pregnancy failure was based on the ments. Couples who had frozen–thawed embryo transfers, a findings of obstetric ultrasound examination(s). First trimester history of recurrent pregnancy failure (3 or more miscarriages), missed miscarriage was defined as an intact gestational sac structural or numerical chromosomal aberrations were ex- lacking any fetal cardiac pulsation [6 weeks after last men- cluded. Women with any medical disorders and/or having con- strual period (LMP)], intrauterine gestational sac with the larg- genital malformation of the uterus were also excluded. est diameter more than 10 mm in the absence of yolk sac or an Please cite this article in press as: Abuelghar WM et al. Risk of first trimester spontaneous miscarriage among singleton gestations following ICSI and its relation to underlying cause of infertility, Middle East Fertil Soc J (2013), http://dx.doi.org/10.1016/j.mefs.2013.06.005 Spontaneous miscarriage among singleton gestations following ICSI 3 Figure 1 Participants flowchart. empty gestational sac with a sure confirmed gestational age of ences) software version 17.0. Descriptive statistics were done