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Treatment of sub-fertile women aged ≥ 40 years old (AMA) is challenging. Co-treatment with growth hormone (GH) is suggested to improve reproductive outcomes in poor responders. However, few studies, and with conflicting results, focused on women with AMA. A systematic review and meta-analysis of randomized controlled trials (RCTs) and comparative retrospective trials (CRTs) of GH cotreatment in AMA women undergoing in vitro fertilization or intracytoplasmic injection treatment using their autologous oocytes was performed. The search included studies published in English up to the end of 2021. The primary outcome was the clinical pregnancy rate per embryo transfer. Secondary outcomes were the number of mature and retrieved oocytes and the rate of live birth. 406 studies were found. The final analysis included three RCTs and four CRTs with 481 patients who used GH and 400 patients who did not. Clinical pregnancy and live birth rates were significantly higher in the GH cotreatment group compared to the placebo as well as the group without GH co-treatment, (OR 2.2; 95% CI 1.34 - 3.61 and OR 4.12; 95% CI 1.82 - 9.32, respectively). Intriguingly, the subgroup analysis showed that poor-responder patients did not benefit from co-treatment with GH. There were no statistically significant differences in the number of mature or retrieved oocytes. GH cotreatment in a subgroup of women with AMA improves clinical pregnancy and live birth per fresh embryo transfer. However, this conclusion must be taken with caution and further research is needed. The review is registered in PROSPERO database (CRD42021252618). www.crd.york.ac.uk/prospero/.

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In vitro fertilization (IVF) cycles are associated with a defective luteal phase. Although progesterone supplementation to treat this problem is standard practice, estrogen addition is debatable. Our aim was to compare pregnancy outcomes in 220 patients undergoing antagonist intracytoplasmic sperm injection (ICSI) cycles protocol. The patients were randomly assigned into two equal groups to receive either vaginal progesterone alone (90 mg once daily) starting on the day of oocyte retrieval for up to 12 weeks if pregnancy occurred or estradiol addition (2 mg twice daily) starting on the same day and continuing up to seven weeks (foetal viability scan). Primary outcomes were pregnancy and ongoing pregnancy rates per embryo transfer. Secondary outcomes were implantation and early pregnancy loss rates. Pregnancy rates showed no significant difference between group 1 (39.09%) and 2 (43.63%) (p value = 0.3). Similarly, both groups were comparable regarding ongoing pregnancy rate (32.7% group 1 and 36.3% group 2, p value = 0.1). Implantation rates showed no difference between group 1 (19.25%) and group 2 (23.44%) (p value = 0.2). Early pregnancy loss rates were comparable, with 6.3% and 7.2% in groups 1 and 2, respectively, (p value = 0.4). In conclusion, the addition of 4 mg estrogen daily to progesterone for luteal support in antagonist ICSI cycles is not beneficial for pregnancy outcome.

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BACKGROUND: Vaginal hysterectomy is considered the method of choice for removal of the uterus but most gynecologists still prefer the abdominal route for removal of benign uteri >14 weeks in size. Conversion of an abdominal to a potential vaginal hysterectomy by uterine size reduction would be advantageous. Gonadotrophin-releasing hormone (GnRH) agonists can reduce uterine bulk by up to 50%. OBJECTIVE: To evaluate the efficacy of the preoperative administration of a GnRH agonist for women with enlarged non-prolapsing uteri in order to facilitate vaginal hysterectomy, in comparison with patients with enlarged uteri who underwent direct total abdominal hysterectomy (TAH) for the same indication (menorrhagia). STUDY DESIGN: Randomized controlled study. Women scheduled for hysterectomy for menorrhagia with a non-prolapsing uterus of ≥14 weeks size (by clinical and sonographic assessments) were offered a trial of vaginal hysterectomy after pre-treatment with a GnRH agonist (goserelin) for 3 months (study group=Group 1=40). A group of women with uteri of comparable size who underwent abdominal hysterectomy for similar indications served as controls (Group 2=40). Pre- and post-operative data such as hemoglobin, myoma size, uterine weight, duration of procedure and complications, pain score and length of hospital stay were collected prospectively. RESULTS: The weight of the uterine specimen was significantly lower in Group 1 (511.7±217g) compared to Group 2 (736.8±212g); P<0.001. The mean objective decrease in clinical uterine bulk preoperatively in Group 1 was 20.1%. The duration of surgery was nearly 1.5 times as long in vaginal (119.6±41.7min) compared to abdominal hysterectomy (81.1±34.1min), P<0.001, but analgesia use and the length of inpatient stay were significantly lower in Group 1 (2.6±1.3 days) compared to Group 2 (4.12±1.7 days), P<0.001. There was no significant difference between the two groups as regards the rate of occurrence of surgical complications. CONCLUSIONS: In women with ≥14 week size uteri, treatment with a GnRH agonist reduces uterine size sufficiently to allow safe vaginal hysterectomy. Although duration of surgery was longer, women who underwent vaginal hysterectomy required less analgesia and had a shorter inpatient stay.

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