Endocrinology: Two cases of ovarian tumours in women who had undergone multiple ovarian stimulation attempts

Concerns have been raised recently about the possible associationbetween superovulation and ovarian cancer. In order to contributeto the limited literature on this important issue, two casesof ovarian tumours in women who had undergone multiple ovulationinductions are presented. In the first case, the patient hadsecondary anovulatory infertility. She was treated with humanmenopausal gonadotrophin (HMG) alone and in combination withclomiphene citrate or buserelin for six cycles. She then underwentovarian stimulation with buserelin/HMG in the long protocolfor in-vitro fertilization (IVF) and embryo transfer. In preparationfor a new IVF/embryo transfer attempt, 8 months later, the screeningultrasound revealed a cystic formation of the left ovary andan enlargement of the right. During laparotomy, both ovarieswere found to bear large tumours (approximately 6x5x4 cm) whichwere removed. Histological examination showed that they wereepithelial tumours (serous-papillary cystadenomas) of borderlinemalignancy. The patient conceived spontaneously 1.5 years afterthe operation. In the second case, the patient presented withsecondary anovulatory infertility. She underwent ovulation inductionwith clomiphene/HMG and with buserelin/HMG in the long protocol,and intra-uterine insemination with husband's spermatozoa andconceived (singleton pregnancy). She was delivered by Caesareansection, during which a cystic tumour of the left ovary wasremoved. Histological examination revealed a benign mucous cystadenomaof the ovary. In conclusion, the clinical information from thesetwo cases does not support a causal association between ovarianstimulation and ovarian tumours but does potntially supporta facilitating one.     

输卵管切除术对体外受精-胚胎移植中卵巢超排卵的影响

目的：探讨输卵管切除术对体外受精-胚胎移植（IVF-ET）超促排卵中卵巢反应性及结局的影响。方法：选择2006年2月至2007年6月在本中心行常规IVF-ET治疗的179例不孕患者为研究对象,共分为A、B、C、D四组,A组为48例单侧输卵管切除患者,B组为41例双侧输卵管切除患者,对照C组为50例双侧输卵管阻塞（不伴积水）患者,对照D组为40例单侧或双侧输卵管积水患者,比较4组患者在IVF-ET周期中卵巢对控制性超排卵的反应及其结局的差异。结果：4组患者的基础FSH水平、窦卵泡数、使用促性腺激素（Gn）的时间、注射hCG日的E2水平、冷冻胚胎数及受精率等指标均无明显差异（P〉0.05）;B组Gn的用量高于其他三组,其中与C组间的差异有显著性（P〈0.05）;A、B两组注射hCG日的卵泡数及获卵数少于C、D两组,差异均有显著性（P〈0.05）;D组临床妊娠率为28.2%,低于B、C组,差异有显著性（P〈0.05）。输卵管切除侧卵巢与对侧卵巢相比,窦卵泡数、注射hCG日卵泡数及最终获卵数要明显少于对侧（P〈0.05）。输卵管双侧切除患者中输卵管切除时间≥2.5年侧的注射hCG日卵泡数及最终获卵数要明显少于切除时间≤1年侧（P〈0.05）。结论：输卵管切除术可改善输卵管积水患者的临床妊娠率,但增加IVF-ET周期中的Gn用量,减少获卵数,降低了超促排卵中卵巢的反应性,并且将随着术后时间的延长进一步降低。     

瘦素及胰岛素样生长因子-Ⅰ与卵泡发育的关系

目的：探讨卵泡液和血清中瘦素（Leptin）与胰岛素样生长因子-I（IGF-I）水平与卵泡发育的关系。方法：应用放射免疫法（RIA）检测67例患者取卵日血清及卵泡液中的Leptin与IGF-I水平。结果：（1）取卵日血清中的Leptin水平为（13．20±5．43）mg／L，显著高于卵泡液中kptin水平（10．86±5．73）mg／L，P〈0．05；卵泡液中的Leptin水平与血清中的Leptin水平呈正相关（r=0．84，P〈0．001）。血清中的IGF-I水平为（7．18±4．58）mg／L，显著高于卵泡液中IGF-I水平（4．36±3．03）mg／L（P〈0．05），卵泡液中的IGF-I水平与血清中的IGF-I水平呈正相关（r=0．79，P〈0．001）；（2）卵巢低反应型者的血清及卵泡液中Leptin水平显著高于卵巢中高反应型者，差异有显著性（P〈0．05）；（3）三种卵巢反应类型的血清及卵泡液中IGF—I水平比较，差异无显著性（P〉0．05）；（4）卵泡液及血清中的Leptin水平与IGF—I水平无明显的相关性（r=-0．079，P〉0．05）及（r=-0．127，P〉0．05）。结论：（1）卵泡液中的Leptin及IGF-I均来自血清；（2）高浓度的Leptin可能抑制卵泡发育，而低浓度的Leptin可能对卵泡发育没有影响；（3）体内IGF-I可能与其受体结合后发挥对卵泡发育的调节作用；（4）Leptin与IGF-I之间无明显相关关系。     

Gamete intrafallopian transfer vs superovulation with intrauterine insemination for the treatment of infertility

Superovulation with intrauterine insemination (SO-IUI) has been suggested as an alternative to gamete intrafallopian transfer (GIFT), despite the absence of controlled or comparative trials. We retrospectively analyzed all GIFT and SO-IUI cycles performed concurrently from January 1985 to August of 1987 at a single university center. Pregnancy rates were significantly better for GIFT than SO-IUI (P<0.001), with an odds ratio of 3.25 (P=0.001). Stepwise multiple logistic regression identifield factors that correlate with pregnancy: absence of endometriosis (P=0.05), infertility<3 years' duration (P=0.002), TMS 30×10⁶ (P=0.005), and treatment with GIFT rather than SO-IUI (P=0.001). These data give a first approximation of the increased efficacy of GIFT versus SO-IUI and provide valuable insight into significant confounding variables to be considered when planning a randomized, prospective trial to evaluate these techniques.     

输卵管切除术对体外受精-胚胎移植中控制性超促排卵的影响

目的：探讨输卵管切除术对体外受精-胚胎移植（IVF-ET）周期超促排卵中卵巢反应性的影响.方法：选择因异位妊娠行一侧输卵管切除、双侧输卵管切除的患者以及双侧输卵管未切除的管性不孕患者,观察在IVF-ET中卵巢对控制性超排卵的反应.结果：3组患者年龄、促性腺激素用量、获卵数、受精数以及妊娠率差异无统计学意义.单侧输卵管切除的患者中输卵管切除侧卵巢获卵数少于对侧,但差异无统计学意义.结论：输卵管切除术对IVF-ET周期中卵巢反应性以及妊娠率无明显影响.输卵管积水患者拟行IVF-ET前预防性切除输卵管是可行的.     

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.     

体外受精-胚胎移植取消周期47例临床分析

目的 :探讨在体外受精 -胚胎移植周期中因卵巢反应不良而取消周期的病因及处理方法。方法 :对2 0 0 0年 1 1月至 2 0 0 1年 1 2月接受超促排卵周期因故而取消周期 47例进行分析 ,选择与取消周期者同日或最接近日进入周期接受超促排卵并完成移植周期的 75例作为对照组。结果 :在超促排卵周期中因卵巢反应不良而取消周期 34例 ,占 6 .9% ,反应不良组平均年龄及不孕年限均较对照组长 (P <0 .0 5) ,基础FSH >8IU/L和 /或E2 >50pg/ml反应不良组明显高于对照组 (P <0 .0 1 ) ,反应不良组Gn起始用量及每日用量均明显高于对照组 ,(P <0 .0 0 1 )。结论 :反应不良的原因为卵巢储备功能低下 ,体内存在Gn抗体 ,原因不明 ;加大Gn剂量、降低GnRH -a用量、合用生长激素为常用处理方法。