Factors responsible for multiple pregnancies after ovarian stimulation and intrauterine insemination with gonadotropins

Purpose: The present study was undertaken in order to analyze possible factors that could be responsible for multiple pregnancies in normoovulatory women undergoing superovulation with gonadotropins and intrauterine artificial insemination. Methods: We retrospectively analyzed several clinical parameters in patients that achieved gestation with this treatment. Patients were divided into two groups depending on sperm origin (husband and donor sperm). Furthermore, they were subclassified as follows: (a) cycles resulting in single pregnancies (n=366), (b) cycles ending in multiple pregnancies (n=126), and (c) a control group composed of unsuccessful cycles (n=366). Results: In cycles employing husband's sperm, the age, number of cycles necessary to reach pregnancy, serum estradiol (E₂) levels, and number of follicles were significantly (P<0.05) different in multiple pregnancies compared to single or nonpregnant cycles. In donor insemination, women with multiple pregnancies were significantly younger than nonpregnant patients. There was a significant increase in the number of follicles developed (P<0.00001) and serum E₂ levels on the day of hCG (P<0.05) in multiple compared to single pregnancies and unsuccessful cycles. The number of motile sperm in the insemination specimen was not different among the established groups. When both types of treatments were grouped, pregnant patients were significantly (P<0.00001) younger than women with failed cycles. In addition, multifetal pregnancies were significantly (P<0.05) more frequent in women <30 years old. E₂ production was significantly (P<0.00008) higher in twin and multifetal pregnancies than in single or nonpregnant cycles. Follicular development was also significantly (P<0.00001) higher in twin and multifetal pregnancies compared to failed cycles. Conclusions: The results suggest that young women (<30 years) who develop more than six follicles with E₂ >1000 pg/ml when stimulated with gonadotropins are at higher risk of multiple gestation. These data may be helpful in preventing this undesired complication of assisted reproduction techniques.     

A randomized trial of letrozole versus clomiphene citrate in women undergoing superovulation

OBJECTIVE: To compare the effects of the aromatase inhibitor letrozole (7.5 mg) and clomiphene citrate (CC; 100 mg) in women undergoing superovulation and IUI. DESIGN: Prospective randomized trial. SETTING: University teaching hospital. PATIENT(S): We studied a total of 238 cycles of superovulation and IUI in women with idiopathic infertility. INTERVENTIONS: Patients were randomized into treatment with 7.5 mg of letrozole daily (74 patients, 115 cycles) or 100 mg of CC daily (80 patients, 123 cycles). MAIN OUTCOME MEASURE(S): Number of follicles, endometrial thickness, pregnancy rate, and miscarriage rate. RESULT(S): The mean age, parity, and duration of infertility in both groups of patients were similar. There was no significant difference between the total number of developing follicles in the letrozole (5.7 +/- 3.7) and in the CC groups (4.8 +/- 2.5). The number of follicles of > or =14 mm and of >18 mm were 2.1 +/- 1.2 and 1.4 +/- 0.7 in the letrozole group, and 1.7 +/- 0.9 and 1.1 +/- 0.5 in the CC group, respectively. No difference was found in the endometrial thickness between the two groups (7.1 +/- 0.2 mm in the letrozole group, 8.2 +/- 5.9 mm in the CC group). The pregnancy rate per cycle was 11.5% in the letrozole group and 8.9% in the CC group. Four of the 11 pregnancies in the CC group resulted in a miscarriage (36.6%). CONCLUSION(S): Superovulation and IUI with letrozole and CC are associated with similar pregnancy rates, but the miscarriage rate is higher with CC. The ideal dose of letrozole remains unknown and further study is needed.     

Inadvertent Superovulation and Intrauterine Insemination During Pregnancy: A Lesson from an Ectopic Gestation

It is believed that follicular development and ovulation is suppressed during the early period of gestation in humans. In this report, we describe a patient who underwent ovarian hyperstimulation following a presumed menstrual bleeding. The case illustrates that the ovaries during early pregnancy seem to respond normally to exogenous gonadotrophin stimulation. Despite ongoing pregnancy, the high plasma concentrations of gonadotrophins have rescued pituitary and ovarian insensitivity. Normal follicular development and even ovulation are allowed to occur. Moreover, it is mandatory to preclude pregnancy before commencing superovulation and assisted reproductive technology.     

GnRHa超排卵对小鼠子宫内膜形态学和雌、孕激素受体表达的影响

探讨 Gn RHa长周期辅助超排卵对小鼠分泌期子宫内膜组织形态和性激素受体表达的影响。方法 :将 40只小鼠随机分成 4组 ,其中 2组给 Gn RHa+h MG+h CG为用药组 ,另 2组为对照组给等体积生理盐水 ,在促排卵和排卵后 2 4、48h利用多功能图象分析仪定量测定子宫内膜厚度、腺体和腺腔面积、周长、最大直径、腺上皮细胞总面积和平均高度 ;SP免疫组化法定量测定腺上皮细胞雌、孕激素受体表达。结果 :( 1 )用药组在注 h CG后 2 4、48h子宫内膜厚度与对照组相比差异无显著性 ( P>0 .0 5 )。 ( 2 )用药组在注 h CG后此两时段腺体和腺腔面积、周长、最大直径以及腺上皮细胞总面积和平均直径均显著小于对照组 ( P均 <0 .0 5 )。同时用药组部分内膜间质和腺体发育不同步。( 3 )用药组在注 h CG后两时段内膜腺上皮细胞 ER、PR免疫组化阳性率和染色强度均显著低于对照组同期值 ( P均 <0 .0 5 )。结论 :Gn RHa辅助超排卵对小鼠子宫内膜组织结构和 ER、PR表达有不利影响 ,提示该方案并不能完全促进生理状态的子宫内膜形成 ,可能为低妊娠率原因之一     

Increased Oocyte Production after Acupuncture Treatment during Superovulation Process in Mice

Objective To investigate whether acupuncture treatment during superovulation process improves ovarian response and increases egg production. Methods ICR female mice aged 12 -5 weeks were divided into control group, anaesthesia group and acupuncture group. Female mice were injected intraperitoneally with pregnant mare＇s serum gonadotropin （PMSG）, followed by human chorionic gonadotropin （hCG） injection 56 h later. Anaesthesia group and acupuncture group were anaesthetized three times by injecting 10% nembutal solution according to 7.5-10.0μl/g weight. Acupuncture group was treated three times with puncture Sanyinjiao Points（SP6） under anaesthesia. After 17 h of hCG injection, eggs were recovered and ovaries were isolated. Matured eggs were counted, ovarian histology and expression of follicle stimulating hormone receptor（FSH-R） in ovary were analyzed. Results Acupuncture treatment statistically increased the number of ovulated eggs. Histological section showed that some matured follicles left in the ovaries of control and anaesthesia groups after ovulation. On the contrary, all matured follicles ruptured and converted into corpus lutea in Acupuncture group. Expression of FSH-R in ovary was decreased in acupuncture group compared with those of the two others. Conclusion Acupuncture treatment during superovulation process improves ovarian response so as to increase egg production. The positive effect of acupuncture may be associated with regulated FSH-R expression.     

血清与卵泡液中血管内皮生长因子在控制性超排卵周期中的变化

目的 本研究通过观察控制性超排卵患者的血清及卵泡液中血管内皮生长因子的变化,探讨血管内皮生长因子与卵泡发育的关系。方法 50个行体外受精-胚胎移植治疗周期的患者为研究对象。分别于月经周期第2天、取卵日抽取静脉血20例,收集取卵日卵泡直径≥18mm或≤16mm卵泡的卵泡液各25例,用酶联免疫吸附试验方法测定VEGF的浓度。结果 取卵日血清VEGF水平(116.9±17.1)mg/L较月经第2天的(92.0±17.2)ng/L明显增高(P<0.001);取卵日卵泡直径≥18mm卵泡液中VEGF水平(1630.6±144.8)ug/L较卵泡直径≤16mm(1475.9±155.5)ng/L高(P<0.05);20例取卵日卵泡液水平(1492.8±184.9)ng/L显著高于同期血清的(116.9±17.1)ng/L(P<0.001)。结论 控制性超排卵周期中血清及卵泡液中VEGF水平均升高,可能参与卵泡发育、卵母细胞成熟。     

归肾丸对DOR小鼠卵巢超微结构的影响

目的 探讨归肾丸对卵巢储备功能低下（diminished ovarian reserve,DOR）小鼠的颗粒细胞超微结构的影响。方法 将20只C57BL/6J雌性小鼠随机分为正常组、模型组、归肾丸组和脱氢表雄酮（DHEA）组。连续序贯腹腔注射孕马血清（PMSG）、人绒毛膜促性腺激素（HCG）、前列腺素F2α（PGF2α）产生连续超数排卵,再结合臭氧吸入构建DOR模型。其后各治疗组给予相应药物灌胃,而正常组与模型组给予生理盐水灌胃。21d后,采用透射电镜观察各组小鼠卵巢颗粒细胞超微结构的变化。结果 模型组中线粒体肿胀明显,还出现了空泡化改变,且较少看到脂滴,各治疗组卵巢超微结构较模型组有明显差异,颗粒细胞线粒体形态规则,管型明显,胞质内脂滴丰富。结论 归肾丸对DOR模型小鼠卵巢超微结构有较明显的改善作用。     

促性腺激素作用下豫医无毛小鼠超排卵效果观察

目的 :探讨近交系豫医无毛小鼠超排卵的最佳条件 ,提高超排卵效果。方法 :30只近交系豫医无毛小鼠随机分为 3组 ,分别用 5IU、8IU、10IU的孕马血清促性腺激素 (PMSG)和人绒毛膜促性腺激素 (HCG) ,间隔 4 8h注射 ,比较排出卵母细胞的数量。结果与结论 :腹腔间隔 4 8h各注射 8IU的PMSG和HCG超排卵效果最好 ;各剂量组右侧卵巢比左侧卵巢超排卵效果好 (P <0 .0 5 )。     

Massive spontaneous superovulation in a sexually mature pig

Ovulation of 97 follicles was recorded in a gilt that had not received any hormonal treatment, and circumstantial evidence adduced for a rapidly proliferating tumour of the adenohypophysis. A lesser degree of superovulation had occurred in the previous oestrous cycle, whilst the rate of follicular development in the current cycle was exceptional. None of the 93 eggs recovered from the oviducts was a primary oocyte, but three were polyspermic pronucleate eggs. The most advanced stage of embryonic development was that of 4-cells. Such a degree of spontaneous superovulation has never been observed before during careful examination of more than 1200 pairs of ovaries from gilts in the same herd.