This prospective randomized controlled trial was conducted at the Reproduction & IVF Center, Obstetrics and Gynecology Hospital, Faculty of Medicine, Cairo University from April 2021 to January 2023. The local Ethics Committee accepted this study protocol on August 19, 2021, approval number MD_238_2021. Two groups of 146 poor female responders to COH patients who were experiencing IVF-ICSI with a GnRH antagonist protocol were randomly allocated. The study (“dual-trigger”) arm included 73 patients who received 10000 units of HCG (Choriomon ®, IBSA 10000 IU) plus 0.2 mg of triptorelin (Decapeptyl, FERRING) and the control (“single-trigger”) arm included 73 patients who received a basic dosage of HCG trigger (10000 units of HCG (Choriomon ®, IBSA 10000 IU)).
The sample size calculation was conducted based on the methodology suggested by Maged et al. [15]. It involved comparing the number of MII oocytes between infertile females with poor ovarian response (POR) who had the IVF cycle with a "dual-trigger" treatment and those who were triggered with a "single-trigger" treatment. The PS computations program, namely version 3.0.11, developed by William D. Dupont and Walton D. from Vanderbilt University in Nashville, Tennessee, USA, was utilized. This study's major result was comparing the quantity of mature oocytes (MII) between the double and HCG trigger groups. The secondary outcomes comprised the total quantity of recovered oocytes, good-quality embryos, and clinical pregnancy rate.
Patients who were POR diagnosed according to the Bologna criteria, poor responders to COH who were experiencing IVF-ICSI with a GnRH antagonist protocol, females with at least two episodes of POR (≤ 3 oocytes with conventional stimulation protocol), and females with Body mass index < 35 kg/m2 were among the inclusion criteria. The exclusion criteria comprised patients who are more than 45 years old, have body mass index > 35 kg/m2, Polycystic Ovaries Syndrome, other metabolic disorders (hyperprolactinemia, etc.), endometriosis, infertility due to severe male impact, and Uterine cavity anomalies.
The demographic data and ICSI cycle data for each included patient were obtained via chart review. All patients selected for ICSI in our study underwent questions about their history, overall examination, baseline 2D transvaginal ultrasound (MINDRAY DP-5), and day 3 Serum samples for FSH, LH, E2, Prolactin, and T.S.H. For all patients, the ovarian stimulation was initiated with fixed antagonist protocol using HMG (human menopausal gonadotropin) in a combination using (Fostimon, IBSA) and (Meriofert, IBSA) in a dose of 300 to 450 IU on day 2 or 3 according to age, BMI, AFC, and Previous trials’ response. Starting from the 6th day of HMG stimulation, a subcutaneous injection of cetrorelix (Cetrotide, Serono) at a dosage of 0.25mg per day was done.
In order to assess the ovarian response, Ovarian ultrasound scans were conducted using a 5.0–9.0 MHz multifrequency transvaginal probe (Mindray DP-5). The scans confirmed that at least two dominant follicles had achieved a diameter of 18 mm, at which point the final maturation of the oocytes was induced using "single and dual-triggers". The harvesting of all oocytes was conducted with the assistance of transvaginal ultrasonography, precisely 35 to 36 hours after triggering. On day 3 after fertilization, Ultrasound-guided fresh embryo transfer was performed. The luteal phase protocol consisted of a daily intramuscular injection of 100mg of progesterone, as well as vaginal medications with 400mg of micronized progesterone (Prontogest, IBSA suppository) administered either vaginally or rectally. This supplementation began on the same day as the retrieval of the oocytes. The level of serum β-hCG was assessed 14 days following oocyte retrieval, and any measurement above 5 IU/mL will be classified as indicative of a positive pregnancy. The administration of 400 mg micronized progesterone vaginally will be completed until the 10th week of gestation for all pregnancies that have been confirmed as positive, following the formation of the luteal-placental shift.
After that, the quantity of collected oocytes and the proportion of mature MII oocytes will be measured in patients from both groups. The presence of chemical pregnancies was verified 2 weeks following the transfer of embryos, through the detection of a positive measurement of serum HCG. Clinical pregnancy is determined by using ultrasound to observe the presence of one or more gestational sacs or by identifying clear clinical indications of pregnancy, often occurring at least 4 weeks after embryo transfer. If there was insufficient follicular growth (< 2 mature follicles) found on cycle day 9, no oocytes were extracted, or if fertilization was unsuccessful, the cycle would be stopped.
The data was statistically characterized using measures such as the mean plus or minus the standard deviation (± SD), the median and interquartile range, or frequencies and percentages when applicable. Due to the non-normal distribution of the data, a comparison of numerical variables between the research groups was conducted using the Mann-Whitney U test. A Chi-square (χ2) test was conducted to compare categorical data. P-values that were less than or equal to 0.05 on both sides were deemed to be statistically significant [16, 17]. The statistical computations were performed using IBM SPSS (Statistical Package for the Social Science) release 22, a computer program developed by IBM Corp, Armonk, NY, USA, specifically designed for statistical analysis. The program was run on Microsoft Windows.