A Clinical And Mechanism Study Of Preventing Ovarian Hyperstimulation Syndrome: Intravenous Calcium Infusion

Objective: To evaluate the effectiveness of intravenous calcium onprevention and treatment of ovarian hyperstimulation syndrome (OHSS) andoutcome in patients undergoing IVF. To explore the prenventive mechanism ofIV calcium by testing the vascular endothelial growth factor (VEGF) andangiotensin II (AT II) level in serum and follicle fluid.Materials and Methods: A randomly prospective trial was performedfrom December2012to January2013in the Second Hospital of HebeiMedical University. Objects were patients with high risks of OHSSundergoing routine long hyperstimulation protocol of IVF or ICSI. Inclusioncriteria were a peak E2level higher than4000pg/ml and more than20leadingfollicles large than14mm on the day of HCG trigger or more than15oocytesobtained. Exclusion criteria were as follows:①a history of systemic disease,endocrinopathies, hypercholesterolemia or neoplasm;②severehydrosalpinges;③patients need coasting for preventing OHSS;④using anymedication such as insulin-sensitizing drugs and GnRH antagonists;⑤patients need cycle cancellation;⑥severe male infertility requiring testicularsperm extraction. There were67patients involved in the study. They weredivided into two groups randomly just after ovum pickup. The patients incalcium group (n=34) were administered IV calcium gluconate (intravenous10%calcium gluconate,10ml in200ml of physiologic saline) on the day ofovum pickup, day1, day2after OPU to prevent OHSS; while the controlgroup (n=33) received no intervention for prevention of OHSS. Before OPU,4ml blood was collected from the ulnar vein, then seperated within one hour toget the serum. The follicle fluid was collected from mature follicles withoutstain. After centrifugating, supernatant was collected. On day3and day8afterOPU, serum was collected with the same method. All of these samples were preserved in-80℃ultra low temperature freezer to test the level of VEGF andangiotensin II at one time. Moreover, fertilization rate, cleavage rate, numberof available embryos, embryos of good quality and mean difference of ovaryvolume in the calcium group were compared with the control group. On thethird day after OPU, it was decided that patients who developed into mild ormoderate OHSS had all their embryos frozen considering their conditionsexcept few persisting. The moderate or severe OHSS rate, transfer rate,chemical pregnancy rate, clinical pregnancy rate and implantation rate in thecalcium group were also compared with the control group. All data wereanalyzed with SPSS19.0software. Statistical significance was set at P <0.05.Results: The basic characteristics such as age, body mass index, d ofinfertility and basic level of serum FSH in both groups were matched. Theconstituent ratios of etiology in the calcium group were similar with thecontrol group. There was no significant difference in duration or comsuptionof controlled ovarian hyperstimulation and serum E2level on the day of HCGtrigger. However, the number of oocytes retrieved in the calcium group wassignificantly higher than that in the control group(24.5±6.13vs20.67±5.39，P=0.008). Then the fertilization rate, cleavage rate, number of availableembryos, embryos of good quality, difference of ovary volume, transfer rateand the number of embryos transferred were compared between the twogroups. The depth of ascites on the third day after OPU in the calcium groupwas significantly lower than that in the control group(38.41±15.42mm vs48.55±19.95mm, P=0.023). There was one patient who developed intomoderate OHSS in either group. Because of great discomfort, the patient inthe calcium group who developed into late OHSS drained3700ml ascites,while the patient in the control group cancelled embryo transfer. The chemicalpregnancy rate, clinical pregnancy rate and implantation rate in the calciumgroup were a little higher, but the differences were not significant. There wasone patient respectively with embryo diapause in both groups. The patient inthe calcium group got twin pregnancy with single embryo diapause, while thepatient in the control group got single embryo diapause. There was no significant difference in the VEGF level in serum and follicle fluid betweenthe two groups on the day of ovum pickup. However, it showed a significantdifference in the VEGF level between the two on day3after OPU(1805.000±1566.974pg/ml vs934.437±801.176pg/ml, P=0.024). On day8after OPU, the calcium group’s VEGF level was similar to the control group’s.The angiotensin II levels of the two groups in serum and follicle fluid werecompared with each other.Conclusions: The results suggested that IV calcium could effectivelyreduce the depth of ascites of patients at high risk of developing into OHSS. Inaddition, IV calcium was thought to be safe to the early outcomes of ART. TheVEGF level of serum was lowered after IV calcium infusion. However, therelationship between the preventive mechanism of IV calcium and AT IIremained unclear which need more further studies.