OHSS is a series of symptoms that the ovarian excessive responses to the exogenous gonadotropins, in which the specific pathogenesis is uncleared it included an increased capillary permeability, a decreased perfusion of essential organs, electrolyte disturbance, and blood concentration(26). The clinical manifestations are bilateral ovarian enlargement, pleural and ascites, abdominal distension, liver, and kidney dysfunction, and other serious complications. VEGF is currently considered a critical factor in the occurrence of OHSS(27). Risk factors for OHSS included (1) patients’ age < 35 years; (2) polycystic ovary syndrome or polycystic ovarian changes; (3) BMI < 18.5 or BMI > 24; (4) AMH > 3.36 ng/ml; (5) sinus follicles numbers: more AFC was also a sensitive indicator for OHSS prediction. (6) The follicular development and oocytes retrieval numbers; (7) With OHSS history in the former cycles. Some studies showed that (28)the OHSS risks for those young infertile patients aged < 35 years were higher than those patients aged > 35 years. Danninger et al. (29) followed 101 patients who received IVF assisted pregnancy and found that patients with OHSS had a significantly lower BMI than those without OHSS. AMH can identify the ovarian reactivity to exogenous gonadotropins during the ovulation cycle. Lee Et al. (30)have found that AMH was a predictor of OHSS when it was higher than 3.36 ng/ml. Jayaprakasan(31)and other researchers have showed the more numbers of AFC for the infertile patients, the more incidence and risks of the moderate to severe OHSS. It is a question that need to be answer in this retrospective study which one was better for the combined treatment or single medication for OHSS prevention and the pregnancy.
4114 cycles were included in this study according to the E2 levels and retrospective analyzed the embryos culture, the transfer cycles cancel and the pregnancy outcomes for the patients using prednisone combined with bromocriptine or single using bromocriptine. It intended to clarify whether the combined treatments may decrease the cycle cancellation rate during the ovulation process and whether it will influence pregnancy outcomes. We found some differences between the two groups in Gn duration and the endometrial thickness on trigger day (Table 2). Although the Gn duration was different, in which lead to the progesterone and LH level differed on the trigger day, there was no statistical difference in the Gn doses and E2 levels between these two groups. As mentioned in the above that the OHSS diagnostic standard, some cycles in this study have the symptoms of a mild OHSS or even some other patients have no any symptoms of the abdominal distension, discomfort, mild nausea/vomiting and diarrhea and just only with a higher E2 level.
As for the fresh transfer cycle cancellation, it was determined to the ovarian size and hormone levels and whether it occurred pelvic effusion or ascites and its degrees. According to the diagnosis of OHSS, physicians determined whether to cancel the cycle based on the patient's B-ultrasound results, follicular developments, ovarian sizes, and hormone testing results. We compared the OHSS cancellation cycle between the combined and control groups and found a significant difference between these two groups. Among 1489 canceled cycles, 648 cycles were in the combined group, and 841 cycles were in the control group, the OHSS cancellation rate in the combined group was 31.45%, while in the control group it was 40.88%. These results showed a statistically significant difference between them and it also indicated that it was better that prednisone combined treatment with bromocriptine than bromocriptine single using for relieving OHSS and dramatically decrease the cancellation rate for the fresh embryo transfer cycle. Besides this, there was no statistical difference in the COS protocol proportion between these two groups, which mainly existed of the agonist protocols, but the antagonist protocols were in the minority.
We compared the embryo qualities and embryo transfer outcomes and we want to know if prednisone combined with bromocriptine better than the single using of bromocriptine. The definition of the high-quality embryo was those embryos of the grade one and grade two. Our transfer standard for embryo transfer was performed according to the embryos quality evaluation by the embryologists and the patients’ ages and heights, the cesarean delivery histories or other operation histories. According to the statistical analysis results, there had no statistical difference for the total number of the high-quality embryos and the blastocyst formation rate between the two groups. The average number of embryos transferred in the combined group was 1.59, while the average number of embryos transferred in the control group was 1.70, which was higher than it in the combined group with a significant statistical difference (Table 5). In terms of the total number of transfer cycles, 846 cycles were in the combined group, while 753 cycles were in the control group. The single embryo transfer in the combined group were 350 transfer cycles, and 495 cycles for double embryos transfer. In the control group, single embryo transfers were 227 cycles and 517 cycles were the double transfer (P < 0.001). In terms of the embryo implantation, the numbers of implanted embryos in the combined group were 509 cycles, while that in the control group were 442 cycles. The implantation rate of the two groups had a statistically difference between them (P = 0.012). The above results all indicated that combined bromocriptine with prednisone would not only relieve the symptom of OHSS but also wouldn’t influence the transferred embryo qualities.
As for the pregnancy outcomes, we found no statistical differences in terms of clinical pregnancy rate, ongoing pregnancy rate, live birth rate, and early miscarriage rate between the two groups. Although the cycles of control group which we transferred just only one embryo were less than that of the combined group, in terms of implantation rate, the results in the combined group was significantly better than it in the control group. It demonstrated that the advantages of selective embryo transfer and the pregnancy outcome may be closely related to the embryo quality itself and little to do with the embryo transfer numbers. Although the fetal malformation occurred in five cycles in the combined group and three cycles in the control group, including congenital heart disease, six-finger deformity, and abdominal fissure malformation, there was no significant difference in the incidence of fetal malformation and ectopic pregnancy between the two groups. Furthermore, there were no significant statistical differences of the rates of biochemical pregnancy and congenital disabilities between the combined and control group.