Abstract

Abstract Study question Does gonadotropin dose adjustment in inadequate ovarian response during controlled ovarian hyperstimulation improve the live birth rates of patients with diminished ovarian reserve? Summary answer The increasing dose adjustment of the gonadotropin according to the ovarian response during COH in DOR provides similar live birth rates to the fixed-dose group. What is known already Since the poor ovarian response is associated with low pregnancy rates and high cycle cancellation rates, the ovarian response should be predicted, especially for stimulation protocol and gonadotropin dose adjustment before COH is initiated. On the other hand, the predicted gonadotropin dose may not be enough for the ovarian response, and the dose adjustment may be required. Nevertheless, the literature has conflicting results on whether dose adjustment during COH improves the pregnancy results. Study design, size, duration This retrospective cohort study was conducted at a tertiary university hospital's ART (assisted reproductive technologies) center. The electronic database of the ART center was screened between the years 2012-2021, and the DOR patients who underwent ICSI-ET (intra-cytoplasmic sperm injection – embryo transfer) were selected. Bologna criteria were used to determine the diminished ovarian reserve. Patients were divided into two groups depending on the presence of dose adjustment on the first ultrasound control during COH. Participants/materials, setting, methods Women who underwent single–fresh good quality (Gardner A or B) blastocyst transfer and aged between 18-40 years, without male infertility and endometrial pathology were included in, and after exclusion, 498 patients were enrolled in the study. Flexible antagonist protocol was used for COH. A vaginal micronized progesterone capsule (3x200 mg) was prescribed for luteal phase support after oocyte retrieval. Live birth rate was determined as the singleton live birth after the 24th week of pregnancy. Main results and the role of chance There were 188 patients in the dose adjustment (DA) group and 310 patients in the fixed-dose (FD) group. The demographic parameters were similar between the groups (Age, Body Mass Index, Ovarian Reserve Parameters). The mean women age was 33.8+4 in the DA group and 33.6+4.1 in the FD group (p = 0.6). The started gonadotropin dose was similar in both groups (300 IU). The type of gonadotropin was mostly HMG in the DA group (67% in DA vs. 48% in the FD group, p = 0.01). The median dose adjustment on the first control was +75 IU in the DA group, and as expected, the total gonadotropin consumption was significantly higher in the DA group (Median values; 3900 vs. 3000 IU, p < 0.01). The follicle output rates, follicle to oocyte indexes, and the embryology parameters were comparable between the groups (number of picked up oocytes, metaphase-2 oocytes, and 2PN embryos). The positive pregnancy rate was 19.7% (36/188) in the DA group vs. 19.1% (61/310) in the FD Group (p = 0.4). The primary outcome of the study; live birth rates were 12% in the DA group vs. 9% in the FD group, and the results were statistically similar (p = 0.3). Limitations, reasons for caution Retrospective design and the sample size limit the power of the study. Wider implications of the findings Our study showed that the gonadotropin dose adjustment in inadequate ovarian response during COH provides similar live birth rates to the fixed-dose group. In patients with inadequate response, dose adjustment may be a necessary action. Trial registration number Not applicable

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