Abstract
ObjectiveTo assess and compare the feasibility of progestin-primed ovarian stimulation (PPOS) protocol with mild stimulation protocol for advanced age women with diminished ovarian reserve (DOR) undergoing their first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle.MethodsPatients aged ≥35 years and DOR undergoing their first IVF/ICSI cycle were enrolled in this retrospective cohort study: 139 and 600 patients underwent the PPOS and mild stimulation protocols, respectively. The primary outcomes were cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLBR). The secondary outcomes were the number of oocytes retrieved and top-quality embryos.ResultsThere was nearly no significant difference of baseline characteristics between the two groups. Although a greater amount of total gonadotropin (1906.61 ± 631.04 IU vs. 997.72 ± 705.73 IU, P<0.001) and longer duration of stimulation (9 (10–7) vs. 6 (8–4), P<0.001) were observed in the PPOS group, the number of retrieved oocytes (3 (6–2) vs. 2 (4–1), P<0.001) and top-quality embryos (1 (2–0) vs. 1 (2–0), P=0.038) was greater in the PPOS group than the mild stimulation group. Meanwhile, the incidence of premature luteinizing hormone (LH) surge rate was significantly lower in the PPOS group (0.7% vs.8.3%, P=0.001) than the mild stimulation group. However, there was no significant difference in conservative CCPR, conservative CLBR, optimistic CCPR, and optimistic CLBR between the two groups (all P>0.05). A multivariate logistic regression model showed significant positive effects of the number of retrieved oocytes and number of top-quality embryos on conservative CCPR (OR=1.236, 95%CI: 1.048–1.456, P=0.012, OR=2.313, 95%CI: 1.676–3.194, P<0.001) and conservative CLBR (OR=1.250, 95%CI: 1.036–1.508, P=0.020, OR=2.634, 95%CI: 1.799–3.857, P<0.001) respectively, while significant negative effects of age were identified for conservative CCPR (OR=0.805, 95%CI: 0.739–0.877, P<0.001) and conservative CLBR (OR=0.797, 95%CI: 0.723–0.879, P<0.001).ConclusionThe PPOS protocol is an effective alternative to the mild stimulation protocol for advanced age patients with DOR, as it provides comparable reproductive outcomes and better control of premature LH surge. Further, more oocytes and top-quality embryos were obtained in the PPOS group, which had a positive association with conservative CCPR and CLBR.
Highlights
With the successive implementation of China’s two-child policy and three-child policy and increasing delays in childbearing age, the number of advanced age women willing to have children is rapidly growing [1]
The results showed that significant positive effects of the number of oocytes retrieved and number of top-quality embryos on conservative CCPR (OR=1.236, 95%confidence intervals (CIs): 1.048–1.456, P=0.012; odds ratios (ORs)=2.313, 95%CI: 1.676–3.194, P
The incidence of premature luteinizing hormone (LH) surge rate and LH levels on the trigger day were significantly lower in the progestin-primed ovarian stimulation (PPOS) group than in the mild stimulation group, which was similar to the results reported in Peng et al’s study [1]
Summary
With the successive implementation of China’s two-child policy and three-child policy and increasing delays in childbearing age, the number of advanced age women willing to have children is rapidly growing [1]. In order to get pregnant, an increasing number of women with advanced age and DOR need to rely on assisted reproductive technology (ART). These women are more prone to poor ovarian response (POR), a premature LH surge, and poor oocyte quality during ART treatment, leading to high cycle cancellation rate, low pregnancy and live birth rate, and high pregnancy loss rate [5]. GnRH antagonist protocol is reportedly associated with about 0.34– 8.0% failure to control premature LH surge in ovulatory women and the predominant risk factors include the increased age, DOR and POR [7]. Mild stimulation IVF has been found to be associated with a higher cycle cancellation rate (CCR), predominantly owing to premature
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