| Part Ⅰ The predictive value of anti-mullerian hormone in pregnancy outcome in women with diminished ovarian reserve in IVF/ICSI treatment cyclesBackground:For females aged over 40 years and younger women with diminished ovarian reserve often had to be confronted with the declination of fecundity, and they might not get desirable outcome in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). As IVF/ICSI-ET is an expensive and invasive technology, it is much of importance and necessary to assess ovarian reserve in order to predict the pregnancy outcome. Most recently published studies had been validated the value of anti-mullerian hormone (AMH) in predicting ovarian reserve and investigated the correlation of serum AMH levels in women with normal ovarian reserve with pregnancy outcome in IVF/ICSI cycles. Seemingly, the value of AMH in predicting pregnancy outcome was not validated externally and was still discriminated, the relationship of AMH with pregnancy outcome from different studies were also contradictory. Moreover, AMH levels in follicular fluids (FF) were thought to be related with oocyte quality and embryo quality more directly, and reflected the pregnancy outcome indirectly. However, as the heterogeneity of FFAMH measurement and study groups were various, the correlation of FFAMH and pregnancy outcome was not yet verified.Objective:This study aimed to compare the anti-mullerian hormone (AMH) levels in serum and follicular fluid (FF) between young women with diminished ovarian reserve (DOR) and women with advanced age (AA,>40yrs), and to investigate the relationship between AMH and oocyte quality and pregnancy outcome.Methods:A total of 149 women undergoing the first IVF/ICSI-ET cycle from October 2013 to June 2014 in Center for Reproductive Medicine, Shandong University were retrospectively studied. Patients were divided into three groups according to ovarian reserve. Group 1 was defined as diminished ovarian reserve (DOR, n=55), diagnosed by young patients (<40yrs) with basal FSH>10 IU/L, and serum AMH<1.5 ng/ml. Group 2 comprised women exceeding 40 years old named as advanced age (AA, n=49).Group3 were infertile women with normal ovarian reserve(<40yrs, FSH>10 IU/L). Collecting the dates on age, body mass index (BMI); on day 2-4 of the menstrual cycle before initiating controlled ovarian hyperstimulation (COH), venipuncture for assay of serum anti-Mullerian hormone, basal endocrine hormone, and transvaginal ultrasound scan for antral follicle count(AFC) were performed. In the study, short protocol was applied for COH in DOR and AA patients, NOR female accepted long protocol. During the COH, a changing dosage of gonadotropin was given in terms of sequential transvaginal sonography and the levels of serum E2、P、LH.6,000-8,000IU of hCG was given when at least two dominant follicles≥18mm in diameter were detected. Oocyte retrieved was carried out 36h after hCG injection, collecting and pooling follicular fluids together. Recording the initial, total dosage and duration of Gn, the number of oocyte retrieved and calculating the fertilization rate, the number of embryo transferred and embryo cryopreserved. Following up the pregnancy outcome and computing the clinical pregnancy rate and live birth rate among three groups, respectively. FFAMH was measured by enzyme-linked immunosorbent assay technique using diagnostic kits.Results:(1) DOR and NOR women were age-matched(32.36±4.20yrs. vs. 31.02±2.80yrs., P<0.05) and younger than AA women(41.67±1.71yrs).Significant difference in age basic FSH (13.36±3.75 IU/L vs.8.45±3.61 IU/L vs.6.69±1.34IU/L, P<0.05) and AFC(7.51±3.5 vs. 7.71±3.18vs. 13.53±4.15, P<0.05) were observed among three groups. AFC was similar between DOR and AA group (P>0.05). BMI and basal E2 levels among three groups were also no significant differences (P>0.05).(2) Both serum AMH and FF AMH concentrations were significantly lower in young patients with DOR and AA groups compared with that in NOR [serum AMH: 0.33ng/ml (0.13,0.49) vs.0.51 ng/ml (0.23,0.93) vs.2.35ng/ml (1.65,2.90); FF AMH: 2.32ng/ml (1.14,4.44) vs.2.66ng/ml (1.48,4.72) vs. 6.77ng/ml (4.56,13.21), p﹤0.01], however, no difference in FFAMH was observed between DOR and AA groups (P>0.05). The peak estrogen (E2) on HCG day in NOR were statistically higher than DOR group and AA (2550.29±608.97 pg/ml> 1890.42±1049.27 pg/ml> 1493.45±667.59 pg/ml) (P<0.05). Fewer number of follicle>14mm and oocytes retrieved were in DOR group and AA group than NOR group (4.41±2.54 vs. 3.53±1.76 vs. 9.13±2.64; 3.76±1.99 vs. 5.47±3.55 vs. 11.22±3.97, respectively, P﹤0.05).(3) The rate of good quality embryo on D2 (51％±34％vs.42％±31％ vs.52％±21％) and fertilization rate (64％±33％vs. 55％±32％vs. 65％±19％) were comparable among three groups(P>0.05). Two-fold higher CPR was found in NOR than DOR group (62.79％vs.38.3％, P﹤0.01), accompanying with remarkably higher LBR (60.47％vs.31.91％, P﹤0.01). The lowest CPR and LBR were observed in AA group (17.5％,7/40; 5.00％,2/40) (P﹤0.01).(4) In DOR group, serum AMH was positively correlated with AFC and number of oocytes retrieved (r=0.46, P﹤0.01; r=0.38, P﹤0.01, respectively) and these positive relationships were also found in AA women(r=0.51, P﹤0.01; r=0.38, P﹤0.01, respectively). But only FFAMH was found to be correlated with number of oocyte retrieved (r=0.42, P﹤0.01) in AA groups. No correlation of serum AMH with CPR and LBR and the rate of good quality embryo on D2 was indicatedamong three groups; neither did FF AMH levels(P>0.05).Conclusion:(1) No association of either serum or follicular fluids AMH with oocyte quality and pregnancy outcome was found. (2) A better pregnancy outcome could be anticipated in younger women with DOR compared with advanced age women over 40yrs old in IVF/ICSI cycles. (3) It suggested that serum AMH be a predictor for oocyte quantity rather than quality, but its predictive value in oocyte quality and pregnancy outcome should not be over interpreted.Part II The impact of cystectomy for ovary benign cyst on pregnancy outcome of IVF/ICSI-ET CycleBackground:Ovary benign cyst used to appear mostly in reproductive women, such as benign ovarian tatamis, cystadenoma, ovarian endometriosis cyst (chocolate cyst of ovary). These cysts not only cause chronic pelvis pains, but also lead to irregular menstruation and infertility.Ovarian benign cystectomy is eligible for definitive diagnosis, alleviating pelvis pains and promoting quality of life. However, surgeries also impair ovary cortex and have a negative impact on ovarian reserve.Previous published reports found that lower AFC was presented after surgeries for ovarian endometriosis cyst and simple benign cyst, and AFC in surgery unilateral was lower than that in contralateral without surgeries.AMH, as a sensitive marker of predicting ovarian reserve was also declined after surgeries. It cannot reach the baseline levels of preoperation, though AMH can have a slight increase in 6 months after surgeries.In IVF/ICSI-ET cycles, women accepting ovarian cyst surgeries had poor ovarian response, fewer retrieved oocytes,and fewer good quality of embryo and the number of embryo cryopreserved. But whether surgeries had an adverse effect on pregnancy outcome or not still remain controversial.Objective:To investigate the impact of previously cystectomy for ovary benign cyst on ovarian reserve and pregnancy outcome in IVF/ICSI cycles.Methods:Retrospectively investigated 622 patients who underwent first IVF/ICSI-ET cycle in our reproductive center from January 2013 to June 2014. There were 153 cases who had been removed ovarian cyst by cystectomy surgeries were recruited as study group, in which 44 cases of ovarian endometriosis cyst,35 cases of benign ovarian teratomas,67 cases of simple cyst and 7 cases of ovarian mucinous cystadenoma. In contrast,469 patients with tubal-factor infertility or male factor were included as control group. The age-matched women in the control group had no ovarian surgeries previously. The indicators of ovarian reserve and pregnancy outcome were analyzed between two groups. The influence of different types of ovarian cysts on ovarian reserve and pregnancy outcome in IVF/ICSI cycles were also studied.Results:(1) The significantly lower serum AMH levels [1.92(1.22,3.34) ng/ml vs. 2.90(1.90,4.20) ng/ml], AFC [12.00(9.00,16.00) vs.13.00(11.00,17.00)], retrieved oocytes (11.87±5.01 vs.13.32±5.54) and the number of embryo cryopreserved [1.00(0.00,4.00) vs.3.00(1.00,5.00)] were found in study group compared with control group (all P<0.05). There was no statistically difference between two group for the following parameters, such as basal FSH level, the total dosage of gonadotropin duration and the total dosage of gonadotropin(P>0.05). A better clinical pregnancy rate was achieved in control group(61.64％,241/391) than that in study group (61.36%,81/132), but no significant difference was existed(P>0.05). (2) Ovarian endometriosis cyst was studied as Group A, and Group B consisted of benign ovarian teratomas, simple ovarian cyst and mucinous cystadenoma. Compared to Group B, Group A had fewer AFC, lower serum AMH levels, retrieved oocytes and the number of embryo cryopreserved [10.57±4.36vs.13.45±4.97; 1.65(1.04, 2.31)ng/ml vs.2.15(1.32,4.10)ng/ml; 9.39±3.90 vs.12.87±5.08]; 0.00(0.00,2.00) vs.2.00(0.00,4.00), respectively, P﹤0.05]. There was a lower clinical pregnancy rate in Group A than that in Group B (50.00％vs.65.96％), accompanying with higher abortion rate (15.79％vs.9.68％), but no differences were observed (P>0.05).Conclusions:(1) Ovarian reserve declines after the cystectomy for ovarian benign cysts and the cystectomy has a negative impact on IVF/ICSI cycles, resulting in a decrease of the number of retrieved oocytes and the number of embryo cryopreserved, but do not influence clinical pregnancy outcome. (2) Ovarian reserve is impaired more seriously by cystectomy for ovarian endometriosis cyst than other ovarian benign cyst. |
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