A retrospective comparison of GNRH administration in addition to HCG for ovulation triggering with standard hcg triggering regarding clinical pregnancy outcomes in combined intrauterine insemination cycles with gonadotropin

OBJECTIVE: A standard single dose 250 mcg recombinant human chorionic gonadotropin (hCG) is administered for final follicular maturation and ovulation triggering, after ovulation induction with gonadotropins for intrauterine insemination (IUI) cycles. hCG has the same effect with the long half-life luteinizing hormone (LH). It has a long luteotropic effect that increases the risk of ovarian hyperstimulation syndrome (OHSS). According to recent studies regarding IVF cycles, gonadotropin relasing hormone (GnRH) agonists are used for final follicular maturation and induction of ovulation in order to prevent OHSS. When the ovulation is triggered with GnRH analogue, the peak of FSH (follicle stimulating hormone) imitates the natural cycle. FSH increases the LH receptors on the granulosa cells for ovulation and improves the maturation of the oocyte nucleus. Concurrently, it contributes to the maturation of the oocyte nucleus by providing the endogenous increase of LH. There are many studies that compares the combined use of 0.2 mg GnRH agonist and hCG with standard hCG regarding ovulation triggering, and it appears that combined use of GnRH and hCG triggering is more associated with increased clinical pregnancy rates than standard hCG triggering. There are many prospective randomized controlled studies concerning IVF cycles. We aimed to establish the relationship between the aforementioned combined ovulation triggering and the clinical pregnancy and OHSS outcomes in gonadotropin-induced IUI cycles in our retrospective study. METHOD: Our study was conducted with cases of primary infertility at the infertility clinic of Dokuz Eylul University School of Medicine. The patients had visited the clinic between October 2017 and October 2018, and their planned treatment was intrauterine insemination combined with gonadotropin administration. Before the initiation of the study, ethical approval of Dokuz Eylül University Non-Invasive Research Ethics Committee had been obtained. The total number of included cases is 74: Group I (standard dose 250 mcg recombinant human chorionic gonadotropin) n=38; Group II (in addition to hCG injection, administration of 0.2 mg GnRH analogue 2 hours later); n: 36. According to the case files, ovulation induction with gonadotropins was administered as follows: Daily subcutaneous injection was performed using recombinant FSH and patientspecific, with individualized planned classical or low-dose step-up protocols. Standard semen parameters were evaluated according to the 2010 guidelines of WHO, morphological examination was analyzed in the laboratory of the Department of Obstetrics and Gynecology, Dokuz Eylul University School of Medicine according to Kruger criteria. According to the case files, the same person prepared the samples for insemination. In both groups, 32-36 hours after the ovulation triggering with hCG, intrauterine insemination was performed. After intrauterine insemination, all patients rested in supine position for 10 minutes. The groups received 600 mg of micronized progesterone, applied intravaginally, divided into three capsules per day, for luteal phase support. Two weeks after the insemination, the patients were tested for pregnancy by serum ß-hCG measurement. Patients with serum ß-hCG values above 25 mIU/mL were evaluated as biochemical pregnancies. The presence of clinical pregnancy was defined as the detection of fetal heart beats on transvaginal ultrasound 3 weeks after ß-hCG value positivity. Medison SonoAce X6 C3-7EP, transvaginal ultrasound probe C2-8 was used for follow-up. Blood samples were collected from Central Laboratory of Dokuz Eylül University School of Medicine and the results were evaluated. RESULTS: Results of 74 couples were examined. Group I consisted of 38 cases, while group II had 36 cases. The mean age of the female patients was 28.9 (20-35) and the mean age of the male patients was 33.2 (22-47). Male smoking habit (package / year) and female smoking habit (package / year) were similar in both groups according to patient histories. Similar results were obtained in terms of history of infertility treatment in both groups. The groups were similar in terms of female age, male age, body mass index (BMI) and duration of infertility. No difference was observed between the groups in terms of infertility. Male factor was the most common cause of infertility in both groups. There was no difference between the groups in terms of basal serum hormone levels. While evaluating intrauterine insemination cycles, stimulation time (day), total gonadotropin dose (IU/day) and triggering day endometrial thickness (mm) criteria were evaluated. There was no difference between the groups in terms of these criteria. There was no difference in sperm parameters between the groups. Both biochemical pregnancy and clinical pregnancy rates were %13.2 in Group I and %27.8 in Group II, but there was no statistical difference between the groups (p= .11). Dichorionic diamniotic multiple pregnancy was detected clinically in 2 cases in Group I (p= .16). Group II had no multiple pregnancies. No cases of OHSS was present in the both groups. DISCUSSION: There were no differences between the groups in terms of clinical and biochemical pregnancy outcomes (p= .11). In Group II, multiple pregnancies were not present. Multiple pregnancies (dichorionic diamniotic twin pregnancy) were detected in two patients in group I (p= .16). When the follow-up forms of the cases with multiple pregnancies were examined, it was determined that there were two follicles that were 16 mm or more in diameter on the trigger day. Cases of OHSS were not present in both groups. Concerning clinical pregnancies and outcomes of OHSS, more prospective randomized studies with larger number of cases are needed. KEYWORDS: Intrauterine insemination, OHSS, triggering GnRH agonist