The effect of progesterone supplementation prior to the induction of ovulation in women treated for in-vitro fertilization

Thirty-one patients superovulated with clomiphene citrate (CC)and human menopausal gonadotrophin (HMG) were given a singleinjection of 25 mg progesterone (P group) 6 h prior to injectionof human chorionic gonadotrophin (HCG). Levels of urinary andplasma luteinizing hormone (LH) were significantly higher (P<0.001)immediately prior to HCG in the P group compared with thirty-onecontrol patients who had HCG on the same night. Plasma levelsof progesterone remained significantly elevated (P<0.02)for 80 h after injection in the P group, thereafter the levelwas similar to controls. The number of oocytes recovered, fertilizedand replaced per patient was identical in both groups. However,four control patients had no embryos replaced due to failedfertilization. It is concluded that (i) in the majority of Ppatients the timing of ovulation induction by HCG injectionwas appropriate as an LH surge was elicited thus reflectinga physiological stage of readiness, and (ii) elevated plasmaprogesterone levels around the time of oocyte recovery and inthe early luteal phase do not increase the likelihood of theestablishment of pregnancy in patients stimulated for in-vitrofertilization and embryo replacement (TVF/ER) with CC and HMG.     

Ovarian stimulation and ovarian tumours: a critical reappraisal

Increased interest has arisen recently about the possible associationbetween ovarian stimulation and ovarian tumours. In this article,the current knowledge on the epidemiology, pathogenesis andaetiology of ovarian tumours is extensively reviewed in relationto the existing literature on the relationship between ovulationinduction and ovarian neoplasia. The available data from epidemiologicalstudies and case reports do not support a direct causa] relationshipbetween ovarian stimulation and ovarian cancer. However, itis possible that ovarian stimulants may have an augmenting rolefor special categories of tumours, e.g. sex-cord stromal tumours.A definite answer to this important issue may be reached throughlarge prospective epidemiological studies or large retrospectivewell-designed case-control studies.     

超促排卵联合宫腔内人工授精对母婴的影响

目的：评估经超促排卵联合宫腔内人工授精（IUI）对妊娠妇女和小儿的影响。方法：对1996年12月至1998年8月在本中心经超促排卵和IUI后的孕妇和小儿进行随访，并以同期自然受孕且正常足月分娩的母婴各20例作为对照。40例妊娠妇女通过电话或书信随访，随访内容包括病史、超排后的反应、妊娠期合并症和分娩等情况。小儿随访包括全身检查、体格发育和智能测试。结果：实验组发生卵巢过度刺激综合征（OHSS）5例，妊娠合并前置胎盘1例，胎膜早破，过期妊娠及产后出血各1例，双胎2例，新生儿畸形1例，对照组孕期合并妊高征、乙肝及胎膜早破各1例。小儿体格发育的各项指标和智能测试均在正常范围，且两组相比差异无显著性（P＞0．05）。结论：超促排卵联合IUI治疗对不育妇女是安全的，对分娩的小儿亦无明显的不育影响。     

PRORENIN AND ACTIVE RENIN CONCENTRATIONS IN OVARIAN FOLLICULAR FLUID INCREASE AFTER THE LH PEAK IN SUPEROVULATED HEIFERS

1. The aim was to analyse the in vivo variations with time of prorenin and active renin and their relationship to steroid hormones in ovarian follicular fluid during follicular growth in heifers. 2. Thirty one beef heifers were assigned to two groups after oestrous synchronization: an unstimulated and a follicle-stimulating hormone (FSH)-treated (superovulated) group. Within each group, animals were slaughtered at different times of the follicular phase of the oestrous cycle. Ovarian follicular fluids were aspirated and analysed for the concentrations of active renin, prorenin, oestradiol-17β (E₂) and progesterone (P₄). 3. Prorenin and active renin concentrations in follicular fluid remained constant until the luteinizing hormone (LH) peak, after which time they increased four- and two-fold, respectively, in superovulated heifers. 4. In follicular fluid, prorenin and active renin correlated negatively with oestradiol and E₂/P₄ ratio but positively with progesterone during follicular growth in superovulated heifers. Prorenin also correlated negatively with oestradiol and E₂/P₄ ratio in unstimulated heifers. 5. The increase of renin concentrations in ovarian follicles after the LH peak and the correlations to steroid hormones suggest an important role of the ovarian renin-angiotensin system in bovine follicular growth and maturation.     

Decreased superovulation in adult mice following neonatal exposures to technical methoxychlor

To examine the effects of technical methoxychlor (MXC) on superovulation, neonatal mice received intraperitoneal (i.p.) injections of either sesame oil, 10 μg of estradiol 17β, or 0.1, 0.5, or 1 mg of technical MXC. At 2 and 4 months, half of the mice received a superovulatory regimen of 10 IU pregnant mare's serum gonadotropin followed by 10 IU human chorionic gonadotropin. The mice were sacrificed 15 to 20 h later, the number of ovulated oocytes were counted, and the ovaries were removed for histology. In the lowest MXC dose, the ovaries appeared normal and at 2 months, ovulated the same number of oocytes as controls. Estradiol or the highest two MXC closes induced ovarian atrophy. Following gonadotropin injections, these ovaries also ovulated oocytes. However, the number of oocytes recovered from experimental mice exhibited a time- and dose-dependent decline, and by 4 months, their number was significantly reduced. Neonatal exposures to MXC reduces ovulatory rates and ovarian functions in adults.     

Effects of growth hormone administration in addition to gonadotrophins in normally ovulating women and polycystic ovary syndrome (PCO) patients.

Follicular fluid sex-steroids, insulin-like growth factor-I (IGF-I), IGF-I binding protein (IGF-I-BP) and epidermal growth factor were investigated in patients with polycystic ovaries and normally ovulating women, following ovulation induction with gonadotrophins or growth hormone plus gonadotrophins. Growth hormone supplementation enhanced the ovarian response to gonadotrophins, and significantly increased follicular fluid IGF-I in both groups, without affecting follicular fluid epidermal growth factor; growth hormone supplementation significantly decreased follicular fluid androstenedione in both groups.     

Blunted LH surge after HCG administration in cycles superovulated for in-vitro fertilization

The preovulatory pattern of serum luteinizing hormone (LH) was investigated in cycles superovulated for in-vitro fertilization (IVF). The method used was immunoradiometric assay which shows no cross-reactivity with human chorionic gonadotrophin (HCG) at concentrations usually found after HCG administration. Of the 245 cycles stimulated by clomiphene citrate + human menopausal gonadotrophin, an endogenous LH surge was observed in 29.8% of the patients shortly prior to the HCG injection. In the post-HCG period, 49.4% of the cycles exhibited a blunted LH rise, whereas in the remaining 20.8% the LH level did not exceed twice the mean preovulatory value. According to the oestradiol-17 beta (E2) and progesterone concentrations, different hormonal patterns were found in patients with pre-HCG and post-HCG elevation of LH. However, the occurrence of a blunted LH surge following HCG administration cannot be attributed to different, HCG-induced secretory patterns of progesterone. There were no significant differences in clinical parameters, the pregnancy rate was slightly but not significantly higher (19.0%) in the post-HCG LH surge group than in the two other groups (13.7%). It is presumed that various factors may contribute to the suspension of preovulatory LH suppression. The possible beneficial influence of a post-HCG surge of LH requires further investigation.     

Superovulation and timed intercourse: can it provide a reasonable alternative for those unable to afford assisted conception?

Superovulation was performed prospectively with pure folliclestimulating hormone (FSH) to a group of 224 infertile patientswith ovulatory factor (51), male factor (60), mild/moderateendometriosis (24) and unexplained infertility (72). The aimwas to produce three or four leading follicles in order to compensatefor a ‘deficient’ factor. Ovulation was inducedwith human chorionic gonadotrophin (HCG) and monitoring wasperformed entirely by serial transvaginal ultrasound on alternatecycles up to a maximum of six cycles (1120 treatment cycles)with intervening cycles being used as self-controls (932 restcycles). A further control group of 56 patients was matchedfor age, category and duration of infertility and was only scannedserially (336 control cycles). Seventyfour pregnancies wereachieved and 54 delivered, giving a cumulative pregnancy rateper couple of 33% and a cumulative take home baby rate of 24%per couple after a maximum of six cycles of treatment. Whencompared with the rest or control cycles, treatment was significantlyeffective for ovulatory (P< 0.001), mild/moderate endometriosis(P< 0.01) and unexplained infertility (P< 0.01) but notfor male infertility. Furthermore, pregnancy was five timesmore likely during the first four treatment cycles (P=0.00006,odds ratio=5) at the expense of a significant multiple pregnancyrate (18.9%) and mild/moderate ovarian hyperstimulation rate(12%). We conclude that four cycles of superovulation shouldbe routinely offered to couples on waiting lists for assistedconception or to those unable to afford it, in anovulatory,mild/moderate endometriosis and unexplained infertility. Theseresults need confirmation by a prospective multi-centre randomizedstudy