A Clinical Study On Administration Of Gonadotrophin Releasing Hormone(GnRH) Antagonist Combined With Gonadotrophin(Gn) For Superovulation

Objective:To investigate the clinical effect of Gonadotrophin Releasing Hormone(GnRH) antagonist combined with Gonadotrophin(Gn) contributing to superovulation in the patients treated with assisted reproduction technology(ART).Methods :Total 32 patients who had underwent IVF (in vitro fertilization) or ICSI (intracytoplasmic sperm injection) during 2006.3-2006.4 in our Reproduction Medicine center were analyzed and they were divided into two groups randomly, study group(11 cases) and control group(21 cases).1. Methods of superovulation: Two groups used Gn to superovulate from day 3 of a menstrual cycle. 11 cases in the study group received GnRH antagonist (Cetrotide) 0.25mg/d on pituitary for down-regulation, their treatment (short protocol) was started on day 5 combind with Gn and ceased on the day that HCG was injected. 21 cases in the contral group received GnRH agonist (Decapeptyle) 0.1 mg/qod on pituitary for down-regulation, their treatment(long protocol) was started on day 21 of the previous menstrual cycle and ceased on the day that HCG was injected.2. Triggering of ovulation: ultrasound monitoring of follicles oogenesis was started on day 7 of a menstrual cycle. Final oocyte maturation was achieved by administration of HCG(10000iu) as soon as mean diameter of the biggest follicle≥18mm or that of more than 2 follicles≥17mm were present in ultrasound, the ratio between the level of serum E₂ and the number of growing follicles (mean diameter≥14mm)≥200pg/ml.3. IVF-ET/ICSI: Oocyte retrieval was carried out 36h after triggering of the final oocytes maturation by HCG, then in vitro, fertilization and embryo transfer (IVF-ET) were performed as a matter of principle. Not more than 2 embryos were transferred to these patients who their age≤35years and they attempt ART in the first. Indexes as follow were recorded: The level of serum LH. E₂, the number of retrieved oocytes, M2 oocytes, 2-pronucleate (2PN) oocytes(undergone ISCI), fertilized oocytes, transferred oocytes, embryos transferred, frozen embryos.4. Luteal supplementation: the luteal phase was supplemented by progesterone( 60mg/d, im)or HCG (2000IU/q2d×4次, im), started on the day oocyte retrieval and continued until 8-12 weeks of gestation or in the presence of a negative pregnancy test.5. Pregnancy diagnosis: the urine pregnancy test was taken on day 14 after embryo transplantation. If positive, ultrasound performed on day 35 afer ET could get the message of fetal development . If ultrasound examination could not find the gestation sac, or the vulue ofβ-HCG was falling , the pregnancy failed and the pregnancy outcome was called biochemistry pregnancy-abortion. Otherwise,the gestation sac were existent under B-mode ultrasonography with or without heart beating, the pregnancy outcome was called clinical pregnancy-abortion.6. Statistical analysis: Data was analyzed by using the software spss11.5. Student t-test was used to sample mean comparison. X²-test was used to group comparison. Differences were considered to be significant if p- value<0.05. Results:1. Comparing of serum LH level on the day HCG injected between the two groups: study group(3.24±3.11), control group(3.18±2.83). There was no statistically significant differences between the two groups(P<0.05).The two proposals have effects on the inhibition of endogenous LH peak. One case in the study group presented praecox LH peak, Oocyte retrieval failed because of earlier ovulation.2. Comparing of serum E2 level on the day HCG injected between the two groups: study group(993.93±685.47), control group(1720.93±625.69), The serum E₂ level in the study group was obviously lower than that of in the group of control, the differences between the two groups have statistical significance (P<0.05) .3. Comparing of effects on ovarian stimulation: the number of retrieved oocytes, M2 oocytes, 2PN oocytes, fertilized oocytes, oocytes transferred, embryos transferred, frozen embryos, oocytes retrieval rate and implantation rate have no statistical difference between the two groups (P>0.05) . The two proposals had equal effects on ovarian stimulation.4. Comparing of implantation rate and pregnancy rate: the implantation rate and pregnancy rate of the study group(23%,25%) were superficially lower than that of the control group(43.8%,50%), however, there was no statistical significance (P>0.05) through statistical management.5. Comparing of complication: there was no ovarian hyperstimulation syndrome (OHSS) occurred in the study group, two cases in the control group developed minor OHSS, no moderate or severe OHSS occurred.6. Comparing of pregnancy outcome: There was no abortion occurred in the study group, two cases among them were pregnant and they delivered 3 babies. There were three cases of miscarriages occurred in the control group, presenting a higher abortion rate.Conclusions: 1. The short GnRHa protocol and the long GnRHA protocol on pituitary fordown-regulation have equal clinical effects on ovarian stimulation.2. GnRHa instantly inhabits the endogenous LH peak with no flare up or smallovary cyst detected.3. Ovary stimulation can be integrated into a whole menstrual cycle and it isavailable, convenient, secure and flexible.4. No ovarian hyperstimulation occured.5. Comparing with the long GnRHA protocol, the short GnRHa protocol onpituitary for down-regulation presented a lower abortion rate.