| Objective To analyze cycle characteristics and endocrinological profiles using PPOS in combination with embryo cryopreservation and ultralong protocol for normal ovarian reserve patients undergoing their first COH cycle and investigate the subsequently pregnancy outcomes of their first embryo transfer cycles,thereby providing rational clinical application of the two ovarian stimulation protocols.Methods A prospective randomized controlled trial was performed in 257 normal ovarian reserve patients in Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from 1 October 2016 to 30 April 2017 and the patients were follow-up until 31 December 2017.Computerized randomization was conducted to assign participants who meet the inclusion criteria into two treatment groups: study group(PPOS group,n=130): h MG and MPA were administered at the beginning of menstrual cycle 3(MC3).Ovulation was co-triggered by a Gn RH-a and a low dose of h CG(1000IU)when dominant follicles matured.Viable embryos were cryopreserved for later transfer;control group(ultralong protocol group,n=127): pituitary down-regulation was obtained by a single long-acting depot dose of Gn RH-a in early follicle phase,ovarian stimulation started after 35 days and h CG(5000IU)was used to trigger.Fresh embryo transfer was the first choice in this group except the patients who had to undergo frozen embryo transfer instead of fresh ones due to some reasons.The embryological outcome such as the number of oocyte retrieved,MII oocytes,top-quality embryos,oocyte retrieval rate and viable embryo rate per oocyte retrieved were measured.The changes of the hormones levels during ovarian stimulations were monitored as well as the incidence of OHSS,h MG dose and h MG duration.Pregnancy outcomes were also compared,for instance,clinical pregnancy rate and implantation rate.Results1.No significant differences were found in the number of oocytes retrieved(11.80±6.53 for the PPOS group versus 11.26±5.62 for the ultralong group,P>0.05)and the number of top-quality embryo(3.91±2.96 for the PPOS group versus 3.40±2.51 for the ultralong group,P>0.05).The oocyte retrieval rate(71.32% for the PPOS group versus 68.59% for the ultralong group,P>0.05)was comparable between the patient cohorts as well as the mature oocyte rate,fertilization rate,and cleavage rate.The proportions of viable embryo rate per oocyte retrieved was 38.20%(586/1534)in the PPOS group and 37.48%(536/1430)in the ultralong protocol group,no significant difference was found either(P>0.05).The stimulation duration and h MG dose in the PPOS group were significantly lower than those in the ultralong protocol group(P<0.05).In the PPOS group,they were 9.12±1.28 days and 2027.88±333.90 IU,while being 11.92±2.25 days and 2672.83±599.45 IU in the control group.There were three women in the ultralong protocol group suffered moderate and severe OHSS,while none of the patients did in the PPOS group.The endocrine characteristics on the first day of gonadotropin stimulation were significantly higher in the PPOS group as pituitary down-regulation was obtained in the ultralong protocol(P<0.05).No one suffered premature LH surge in both groups.2.237 women across both groups completed a total of 316 embryo transfer cycles during the follow-up time.There was no significant difference in the clinical pregnancy rate(58.75% for the PPOS group versus 57.69% for the ultralong protocol group,P>0.05),the implantation rate(39.93% for the PPOS group versus 39.66% for the ultralong protocol group,P>0.05)and the cumulative pregnancy rate(66.92% for the PPOS group versus 62.20% for the ultralong protocol group,P>0.05)between the two groups.A further comparation of their first embryo transfer cycles were made and no significant difference was found in the clinical pregnancy rate(56.52% for the PPOS group versus 57.02% for the ultralong protocol group,P>0.05)and the implantation rate(38.01% for the PPOS group versus 39.15% for the ultralong protocol group,P>0.05)between the two groups.However,the endometrium thickness was significantly higher in the ultralong protocol group than that in the PPOS group(12.25±2.60 versus 11.48±2.40,P<0.05)while using different endometrium preparations.When comparing the pregnancy outcomes of the first frozen embryo transfer cycles in the two groups,the result showed no significant difference in the clinical pregnancy(56.52% for the PPOS group versus 69.57% for the ultralong protocol group,P>0.05)and the implantation rate(38.01% for the PPOS group versus 48.89% for the ultralong protocol group,P>0.05),as well as the endometrial thickness(11.48±2.40 versus 10.99±1.76,P>0.05).Conclusion1.PPOS in combination with embryo cryopreservation can achieve comparable number of oocyte retrieved to ultralong protocol while being effective to prevent the premature LH surge in normal ovarian reserve patients,and the embryos originating from PPOS had identical developmental potential to those from the ultralong protocol.2.PPOS is a more efficient ovarian stimulation protocol of less dosage of h MG administration and less duration of h MG during COH with higher cumulative pregnancy rate when comparing to ultralong protocol.3.Being a new ovarian stimulation protocol based on freeze-all strategy,PPOS can obtain similar clinical outcomes compared with Gn RH-a long protocol and reduce the risk of moderate and severe OHSS.It could be an appropriate alternative of the treatments for infertile patients with normal ovarian reserve undergoing IVF. |
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