| With the development of ART, more and more professors are focusing on its security which includes newborns and their mothers. Ovarian hyperstimulation syndrome (OHSS) is a serious potential lethality iatrogenic complication which occurs in the process of controlled ovarian stimulation (COS), especially after the day of HCG administration. According to the time, it can be divided into two types:early onset OHSS and late onset OHSS, and it has been supported that early type has more connection with COS than the late type. Although there has been not definite pathogenesis about it till now, the vascular endothelial growth factor(VEGF),which has the ability to proliferate the vessel and vascular endothelium, has been thought to play a key role in OHSS. With the increasing of the vascular permeability, the fluid leaks into the third space of the body, which results the blood concentration increased, the hypovolemia, the electrolyte disturbance and so on. In some serious cases, the patients with severe OHSS may suffer from embolism, liver and nephron dysfunctions and acute respiratory distress syndrome (ARDS), etc, which threat the security of their life. So, it is more important to prevent it. Coasting is one of the methods which are used to prevent OHSS and widely accepted by most of foreign professors. It is a strategy that it involves withdrawing exogenous gonadotropins postponing HCG administration until the patient’s serum estradiol (E2) decrease to a "safe" level when there is too much follicle developed and/or too high E2level during the COS process. It has the advantage that it would not bring more physiological, psychological and economical burden to the patients, but in the same time, its clinical outcome seems unstable.Our study respectively analysed the clinical characteristics and outcomes of coasting in IVF-ET cycles which was used luteal long protocol in COS. and we hoped to give some advise for this prevention strategy.Part Ⅰ the analysis of clinical characteristics and outcome of coasting in IVF-ET cycles with GnRHa long protocolObjective:To summary the characteristics and clinical outcomes of coasting cycles in our center, and to compare them between pregnant and non-pregnant groups. It was expected to be helpful to apply this method in preventing OHSS.Materials and methods:Total124coasting cycles were included in our study from Jan2005to Dec2011. The inclusion standards were those as following:using luteal long protocol in COS; withdrawing Gn but continuing using GnRHa until HCG administration. And the exclusion standards were those as following:the cycles with GnRHant or short protocol where coasting was used; withdrawing Gn without permission. The ages of the infertility women in our study were from21years old to39years old; the infertility durations were from1to13years; the etiology of the patients included: female factors(pelvic diseases, endomeriosis, ovulation failure),male factors, both male and female factors and unknown factors.COS was performed using long GnRH agonist down-regulation protocol. Gn was withdrawn when serum E2level was higher than3000pg/ml and/or the total number of≥10mm follicles was more than30. The E2concentration was evaluated at8-10AM, and the follicle situation was monitored by vaginal B ultrasound. HCG was administrated when the serum E2decreased to a safe level, and there were2to3main follicles which size was≥16mm. The does of HCG was4000to6000IU.35to36hours later, the follicles were punctured.4to6hours after retrieval, granulose cells in the outside layer of oocytes were removed, when the indications for intracytoplasmic sperm injection (ICSI) were fit based on previous or present results of semen, the morphology and the maturity of the oocytes were observed. If there were no ICSI indications, conventional IVF was applied. The fertilization rate of oocytes and the status of embro development were observed and recored. On the third day after oocyte retrieval, the good embryos were chosen to be transferred, and the left were frozed.We analysed the clinical characteristics and outcomes of total124coasting cycles; and compared them between pregnant and non-pregnant groups. SPSS13.0software was applied. Date was expressed by mean±standard deviation, and analyzed statistically using one-way ANOVA and chi-square test. P<0.05was accepted as indication of statistical significance.Results:1.There were64IVF cycles,50ICIS cycles and10IVF+ICSI cycles in this study. Half of the women were the patients with PCO or PCOS. The beginning does of Gn was (186.1±63.5) IU/ml, the mean duration of COS was (10.4±2.4) day, we began coasting when the serum E2was on the mean level of (3602.0±1976.9)pg/ml, and in the same time, the numble of≥14mm follicles was (12.3±5.1). On the HCG day, the mean level of E2was (2836.8±1751.4)pg/ml, and the number of≥14mm follicles was (16.4±5.4). The oocyte retrieved rate was46.6%(1939/4165)..In the ICSI cycles, the mature oocyte rate was83.1%(624/773), the fertilization rate was69.9%(449/642); in the IVF cycles, the fertilization rate was66.8%(773/1157). The D2cleavage rate was96.6%(1181/1222). The mean number of good embryos was (3.7±3.4).The embryo transferring of12cycles were cancelled, the cancellation rate was9.7%(12/124). In the12cycles, there was respectively one case of thin endometrium, endometrial polyp and transferring difficulty. The cancellation reason of other three cases was uterus effusion, and the reason of six cases was for prevention of OHSS.64cycles of patients got clinical pregnancy, the clinical pregnancy rate was57.1%(64/112), the implantation rate was38.2%(92/241). Three patients suffered early natural abortion, one late abortion, and one ectopic pregnancy respectively.Just only one case of severe late OHSS happened in total124cycles, it was suggested to have more relationship with pregnancy; and six moderate OHSS happened. The incidence of severe OHSS was0.8%(1/124), and the moderate was4.8%(6/124).2.The patients in pregnant group were younger and have more antrol follicle count (AFC) than patients in non-pregnant group(P<0.05); and there were no significance on the infertility duration, the percentage of PCO or PCOS cycles, basal FSH,LH and E2level, and treatment indicators between these two groups (P>0.05). The oocyte retrieved rate of pregnant group was higher than that in non-pregnant group(P<0.05). In the ICSI cycyles, the mature oocyte rate and normal fertilization rate of pregnant group were higher than non-pregnant group (P<0.05). The normal fertilization rate of IVF cycles and the D2cleavage rate of total cycles were no significance between the two groups (P>0.05). And there were also no significance on the mean number of transferred embryos and good transferred embryos (P>0.05).Conclusions:it was supposed to apply coasting in the IVF cycles whose patients have the high risk of OHSS. It can prevent moderate and severe OHSS effectively, and not affect the qualities of oocytes and embryos, and the clinical outcomes.Part Ⅱ the effect of serum E2variation on the clinical outcomes in coasting cyclesObjective:To investigate the serum E2concentration variety in the coasting cycles, and to compare the clinical characteristics and outcomes in the E2variety groups.Materials and methods:The124cycles were divided into three groups according to the variety of serum E2during the coasting period:E2decreased>50%group (n=34); E2decreased0～50%group (n=45); and E2increased group (n=45). The statistical method was the same as it used in Part I.Results1. the relationship between serum E2level and coasting duration.Totally speaking, the serum E2concentration on the initiated day was above3000pg/ml, and the higher the initiated E2level was, the longer the coasting duration was. The mean E2level on HCG day decreased, and was below3000pg/ml. During the two days coasting periods, serum E2level increased a little before decreasing.2. the clinical characteristics and treatment outcomes in the three different E2variation groupsAfter1to3days coasting, there were45E2increasing cycles (36.3%,45/124).E2decreased>50%group had more AFC than other two groups(P<0.05). there were no significance on the age, the infertility duration, the percentage of PCO or PCOS patients, the BMI, the basal FSH,LH and E2(P<0.05). There were no differences on the initial Gn does, the total Gn does and the E2level on the coasting initial day(P>0.05). The duration of coasting prolonged with the E2decreasing range extended., and the variety trends of LH and P were the same as E2, both of the different has statistical significance(P<0.05).There were no differences on the number of>14mm, and10-13mm follicles on coasting initial day and HCG day among groups(P>0.05); the oocyte retrieval rate of E2decreased>50%group was the lest in three groups(P<0.05).In the ICSI cycles, there was significant difference in three groups on the oocyte maturation rate (P<0.05); but there were no differences on the normal fertilization rate and the D2cleavage rate in both IVF and ICSI cycles in these groups(P>0.05).Although there was significant difference on the number of available embryos in three groups, the P value was close to0.05(P=0.048), the E2level decreased>50%group was less than other two groups. There were no differences on the number of good embryos and frozen embryos in these groups (p<0.05).There were no significant differences on the cycle cancellation rate, the incidence of middle and severe OHSS, the clinical pregnancy rate and the embryo implantation rate(P>0.05).Conclusions:1.Coasting1to3days is an effective strategy to prevent OHSS, especially in some ovarian hyperrespondence cycles. During the period of coasting, the E2level in some cycles may increase before decreasing, and in other cycles, the E2level on HCG day may still be higher than it on the initiated day.2. Althouth the E2level increased a little after coasting, there was no significant increasing of the incidence of moderate and severe OHSS. 3. The range of E2decreasing would effect the quantity of the oocytes, instead of the clinical outcomes.Part Ⅲ the effect of the duration of coasting on the quality of oocytes, embryos and the clinical outcomesObjective:To investigate the clinical characteristics and the effect of the coasting duration on the quality of oocytes and embryos, and clinical outcomes.Materials and methods:The total124cycles were divided into two groups according to the duration of coasting,1day group(n=84) and>1day group(n=40). The statistical method was the same as Part Ⅰ.Results:1.the comparison of clinical characteristics between these two groupsThere were no difference on the age, the infertility duration, the percentage of PCO or PCOS patients, the BMI, the basal FSH,LH and E2(P<0.05).The E2level on the coasting initial day of>1day group was higher than that of day1group (P<0.05); but there were no significant difference on the indicators of COS protocol and the E2,LH and P level on the HCG day(P>0.05).There were significant differences on the number of>14mm follicles and the oocyte retrieval rate, the>1day group had much more follicles but lower oocyte retrieval rate (P<0.05).2. The comparison of treatment outcome between these two groupsIn the ICSI cycles, there were no significant differences on the mature oocyte rate and the normal fertilization rate between these two groups (P<0.05).. On the IVF cycles, the normal fertilization rate of>1day group was a little higher than day1 group(P=0.045). The D2cleavage rate of>1day group was also higher than day1group, the difference was significant (P<0.05). But there were no significant difference on the number of available embryos, the number of frozen embryos, and the number of good embryos (P>0.05).The cycle cancellation rate between dayl and>1day group was significant difference(P<0.05). There were no significant differences on the incidence of moderate and severe OHSS, the clinical pregnancy rate and the embryo implantation rate (P>0.05).3.There were only two coasting3days cycles enrolled in our study. After withholding Gn, the E2level decreased sharply. Although there were40and60follicles punctured, the oocytes retrieved rate were7.5%(3/40) and15.0%(9/60). Both of these two cycles were treated with ICSI, the MII rate were33.3%(1/3) and100%(9/9) respectively. And the normal fertilization rate were100%(1/1) and55.6%(5/9). In day3, there were1and2good embryos which were all used to be transferred in the fresh cycles. The patient who got2good embryos had pregnancy at last. Both of these two women didn’t get OHSS.Conclusions:1. The duration of coasting lasting1to3days may affect the quantity of oocyte, but there seems to be not significant negative influence on the quality of oocytes, embryos and clinical outcomes.2.For those cycles whose E2decreased sharply after coasting, if we would continue transferring fresh embryo, it had not bad outcome. |
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