Low-dose HCG may improve pregnancy rates and lower OHSS in antagonist cycles: a meta-analysis

Human chorionic gonadotrophin (HCG) may substitute FSH to complete follicular growth in IVF cycles. This may be useful in the prevention of ovarian hyperstimulation syndrome. Relevant studies were identified on Medline. To evaluate outcomes, a meta-analysis of low-dose HCG-supplemented IVF cycles versus non-supplemented ones was performed with data from 435 patients undergoing IVF who were administered low-dose HCG in various agonist and antagonist protocols and from 597 conservatively treated patients who served, as control subjects. Using these published data, a decision analysis evaluated four different management strategies. Effectiveness and economic outcomes were assessed by FSH consumption, clinical pregnancy and incremental cost-effectiveness ratios. Clinical pregnancy and ovarian hyperstimulation were the main outcome measures. Nine trials published in 2002–2007 were included. From the prospective studies, in the gonadotrophin-releasing hormone antagonist group, a trend for significance in clinical pregnancy rate was evident (odds ratio [OR], 1.54; 95% confidence interval [CI], 0.98–2.42). Ovarian hyperstimulation was less significant in the antagonist low-dose HCG protocol compared with the non-supplemented agonist protocol (OR 0.30; 95% CI 0.09–0.96). Less FSH was consumed in the low-dose HCG group but this difference was not statistically significant. Low-dose HCG supplementation may improve pregnancy rates in antagonist protocols. Overall, low-dose HCG-supplemented protocols are a cost-effective strategy.     

The effect of intra-ovarian androgen priming on ovarian reserve parameters in Bologna poor responders

Research questionWhat are the effects of long-term androgen priming in Bologna criteria poor ovarian reserve (POR) patients undergoing IVF?DesignThis open-label pilot study was conducted at IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam. It included consecutive patients aged 18–41 years who fulfilled Bologna criteria for POR undergoing intra-ovarian androgen priming and ultra-long down-regulation with a gonadotrophin-releasing hormone agonist (GnRHa), followed by stimulation with gonadotrophins and GnRH antagonist co-treatment for IVF (n = 30). Priming consisted of low-dose recombinant human chorionic gonadotrophin (rHCG) 260 IU every second day plus letrozole 2.5 mg/day, both for 8 weeks; priming stopped on the first day of ovarian stimulation. The primary endpoint was serum anti-Müllerian hormone (AMH) concentration 8 weeks after priming. Secondary endpoints included antral follicle count (AFC) (2–10 mm), serum human chorionic gonadotrophin (HCG), testosterone and progesterone levels.ResultsCirculating testosterone, progesterone, oestradiol and HCG levels remained unchanged during androgen priming; the mean AMH level decreased steadily from 0.49 ng/ml (baseline) to 0.33 ng/ml (8 weeks). AFC was 4–5 throughout the study. A mean of 1.1 ± 0.9 good transferable embryos were obtained; embryo transfer was performed in 15 patients; no ongoing pregnancies were obtained.ConclusionsLong-term intra-ovarian androgen priming in the current set-up had no significant effect on hormone levels, AFC and recruitable follicles after ovarian stimulation in Bologna POR patients undergoing IVF. Further studies are needed to explore other androgen priming protocols and the clinical value of priming regimens in IVF.     

HMG versus recombinant FSH plus recombinant LH in ovarian stimulation for IVF: does the source of LH preparation matter?

Studies on the role of LH supplementation in patients undergoing assisted reproductive technique use different sources of LH bioactivity-containing preparations, daily doses and modes of administration. This review aims to critically present the available evidence comparing the effect of the two commercially available LH preparations (human menopausal gonadotrophin [HMG] and recombinant FSH + recombinant LH) with different sources of intrinsic LH bioactivity (HCG versus LH, respectively) on ovarian stimulation characteristics and IVF cycle outcomes. A literature review was conducted for all relevant articles reporting on IVF and intracytoplasmic sperm injection treatment outcome after ovarian stimulation using HMG or recombinant FSH plus recombinant LH. The available studies are mostly observational, using different daily doses and modes of administration. No statistically significant differences were observed in ovarian stimulation variables and clinical pregnancy and live birth rates when HMG was compared with recombinant FSH + recombinant LH. Moreover, combined analysis of all the available prospective and retrospective studies produced no firm conclusions in favour of either source of LH bioactivity. Further large randomized controlled studies are needed to investigate the effect of the LH source on IVF outcome and to identify patients who are most likely to benefit from the addition of LH bioactivity supplementation.     

A fixed stimulation protocol for in vitro fertilization (IVF) without determinations of hormones in blood

A new fixed schedule of ovarian stimulation for IVF was developed, which is not only simpler and easier to handle for the patients but also yields better fertilization and pregnancy rates. The period and beginning of stimulation are shifted by means of a contraceptive pill, so that stimulation can generally be started on a Sunday. The patient takes 100 mg clomiphene for 5 days and 7.5 mg prednisolone for 30 days to suppress possible exaggerated adrenal androgens; she also receives 150 IU of human menopausal gonadotropin (HMG) i.m. every other day from her family physician. From the 8th day of stimulation onwards, follicular growth is registered by daily ultrasound at the IVF center. When the dominant follicle exceeds 18 mm in diameter, 5000 IU human chorionic gonadotrophin (hCG) is given. Blood sampling for hormone estimations is not necessary, and only one sample of urine is needed for the LH estimation before hCG. In comparison to clomiphene citrate (Clomid) alone, Clomid plus HMG/FSH and HMG/FSH alone, this protocol resulted in significantly higher fertilization and pregnancy rates per follicular puncture. The rate of abortions and extrauterine pregnancies, on the other hand decreased. When comparing repetitive IVF cycles with the first IVF cycle, a significant reduction of oocytes in repetitions was found, but no difference was found in the number of fertilized eggs. The pregnancy rate, on the other hand, increased in the repeat cycles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Concentrations of gonadotrophins and steroids in pre-ovulatory follicular fluid and serum in relation to stimulation protocol and outcome of assisted reproduction treatment

In this prospective, randomized study, concentrations of gonadotrophins and steroids in pre-ovulatory follicular fluid (FF) and serum were related to type of stimulation protocol as well as to the outcome of assisted reproduction in 280 women subjected to the long protocol gonadotrophin-releasing hormone (GnRH) agonist pituitary down-regulation and ovarian stimulation with either human menopausal gonadotrophin (HMG) or recombinant FSH. In the women treated with HMG, concentrations of LH, FSH, oestradiol and androstenedione in FF were significantly higher, and those of human chorionic gonadotrophin (HCG) and progesterone significantly lower, than in the women treated with recombinant FSH (rFSH). More women became pregnant and delivered in the HMG than in the rFSH group. These differences, however, were not statistically significant. Concentrations of FSH in serum and of FSH and LH in FF were significantly higher in conception than in non-conception cycles, whereas all other hormone concentrations in FF and serum were similar. The present study demonstrates that the pre-ovulatory follicular fluid hormone profile is significantly influenced by the gonadotrophin preparation used for ovarian stimulation, and suggests that ovarian stimulation with HMG results in an intra-follicular hormone profile more similar to that characterizing conception cycles than stimulation with rFSH. However, as the present data represent means of FF hormone profiles, they do not allow the conclusion of a direct correlation between the intra-follicular concentration of a certain hormone and the ability of the corresponding embryo to implant and establish an ongoing pregnancy.     

Results of controlled ovarian stimulation for ART in poor responders according to the short protocol using different gonadotrophins combinations

Introduction Improving pregnancy rates in intricate cases of ovarian stimulation remains a challenge during IVF and intracytoplasmic sperm injection (ICSI). Different protocols of ovulation induction have been proposed.Methods The short protocol of ovarian stimulation using recombinant follicle-stimulating hormone (rFSH) with or without the use of luteinizing hormone (LH) in IVF or ICSI outcome in patients with many failed attempts and maternity age 37 years was investigated. The prognostic significance of high but normal values of day 3 serum FSH concentrations was also evaluated.Results Results show that FSH levels of >9 mIU/ml are associated with poor results even with the use of human menopausal gonadotrophin (HMG). Results were generally comparable when rFSH was used alone or in combination with HMG, except for the quality and the number of embryos transferred, the later being better in the rFSH + HMG group.Conclusion In conclusion intricate cases have good chances for achieving a pregnancy using the short protocol and the outcome is further improved when LH is added from the beginning of ovarian stimulation. A slight elevation of day 3 FSH seems to be a strong prognostic factor for a poor outcome.     

Combination of recombinant follicle stimulating hormone with human menopausal gonadotrophin or recombinant luteinizing hormone in a long gonadotrophin-releasing hormone agonist protocol: a retrospective study

Purpose

To assess the effect of supplementation with recombinant human luteinizing hormone (rhLH) for patients treated either with recombinant follicle stimulating hormone (rFSH) plus rhLH or with rFSH plus human menopausal gonadotrophin (HMG) in a long gonadotrophin-releasing hormone (GnRH) agonist-stimulation protocol.

Methods

A single-centre, retrospective analysis of patients with hypo responsiveness to a long GnRH agonist protocol (n?=?174), with consecutive in-vitro fertilization or intracytoplasmic sperm injection cycles, compared the outcomes of long luteal GnRH agonist ovarian stimulation using rFSH combined with HMG (n?=?100) versus rFSH combined with rhLH (n?=?74). The endpoints included clinical pregnancy, number of oocytes retrieved, and total gonadotrophin dose.

Results

Significantly more clinical pregnancies were achieved after stimulation with rFSH and rhLH than after stimulation with rFSH and HMG (35.1 vs. 19%, p?<?0.01). More oocytes were recovered (13.1 vs. 11.3, p?=?0.024) with less FSH utilized in the rFSH and rhLH group than in the rFSH and HMG group (2706.4 vs. 4134.2?U, p?<?0.001).

Conclusions

Use of rFSH combined with rhLH in long GnRH agonist assisted reproductive technology (ART) cycles was associated with more clinical pregnancies, recovery of more oocytes, and reduction in gonadotrophin use, suggesting that the superior purity and consistency of rFSH and rhLH may result in better clinical outcomes.     

Randomized controlled pilot trial of luteal phase recombinant FSH stimulation in poor responders

This study investigated whether luteal phase initiation of FSH supplementation would improve oocyte yield compared with follicular phase administration in women with poor ovarian response (POR). A two-arm, randomized, open-label pilot trial was performed at a university-based infertility centre. In nine of 18 infertile women with a history of POR in a previous cycle [<5 follicles on day of human chorionic gonadotrophin (HCG) administration; <5 oocytes retrieved; previous IVF cycle cancellation due to POR] FSH was administered during the mid-luteal phase of the preceding menstrual cycle. The primary outcome measure was the number of oocytes retrieved. Secondary endpoints included: follicles >10 mm and >16 mm and oestradiol concentration on the day of HCG administration, peak oestrogen concentration, pregnancy and live birth rates. All endpoints comparing luteal versus follicular stimulation were similar. In paired analysis of patients in the luteal arm compared with the prior cycle, there was a significant increase in days of stimulation (P = 0.01) and number of follicles >10 mm (P = 0.02) and >16 mm (P = 0.02) on day of HCG administration. IVF outcomes with luteal phase FSH compared with follicular phase FSH were similar. Luteal phase initiation of FSH is a safe and potential alternative protocol in poor responders.     

Adding human menopausal gonadotrophin to antagonist protocols – is there a benefit?

The objective of this retrospective analysis was to compare the clinical outcomes of recombinant FSH (r-FSH) with combination r-FSH plus human menopausal gonadotrophin (HMG) protocols in a large private practice using a single IVF laboratory, from 2001 to 2003. Patients underwent ovarian stimulation by standard gonadotrophin-releasing hormone (GnRH) antagonist protocol using r-FSH or combination r-FSH plus HMG. When two or more follicles had attained a minimum mean diameter of 20 mm, follicular triggering was achieved with either recombinant HCG (r-HCG; Ovidrel, 250 microg s.c.) or urinary HCG (u-HCG; 10,000 IU i.m.). The main outcome measures were number of oocytes retrieved and clinical pregnancy rate. There was a lower percentage of cancelled cycles and an increased number of oocytes retrieved, mature oocytes, oocytes that fertilized, embryo that cleaved and a tendency towards higher clinical pregnancy rates in patients treated with r-FSH alone compared with those treated with r-FSH plus HMG. Patients treated with r-FSH plus HMG had lower miscarriage rates and the live birth rate was similar in both treatment groups. In conclusion, irrespective of age, using a treatment regimen consisting of a combination of HMG plus r-FSH was not beneficial compared with r-FSH alone in patients using a GnRH antagonist protocol.     

Ovarian responses to recombinant FSH or HMG in normogonadotrophic women following pituitary desensitization by a depot GnRH agonist for assisted reproduction

At present, there is considerable debate about the utility of supplemental LH in assisted reproduction treatment. In order to explore this, the present authors used a depot gonadotrophin-releasing hormone agonist (GnRHa) protocol combined with recombinant human FSH (rhFSH) or human menopausal gonadotrophin (HMG) in patients undergoing intracytoplasmic sperm injection (ICSI). The response to either rhFSH (75 IU FSH/ampoule; group rhFSH, 25 patients) or HMG (75 IU FSH and 75 IU LH/ampoule; group HMG, 25 patients) was compared in normo-ovulatory women suppressed with a depot triptorelin injection and candidates for ICSI. A fixed regimen of 150 IU rhFSH or HMG was administered in the first 14 days of treatment. Treatment was monitored with transvaginal pelvic ultrasonographic scans and serum measurement of FSH, LH, oestradiol, androstenedione, testosterone, progesterone, inhibin A, inhibin B and human chorionic gonadotrophin (HCG) at 2-day intervals. Although oestradiol serum concentrations on the day of HCG injection were similar, both the duration of treatment and the per cycle gonadotrophin dose were lower in group HMG. In the initial 16 days of gonadotrophin treatment, the area under the curve (AUC) of LH, oestradiol, androstenedione and inhibin B were higher in group HMG; no differences were seen for the remaining hormones measured, including the inhibin B:inhibin A ratio. The dynamics of ovarian follicle development during gonadotrophin treatment were similar in both study groups, but there were more leading follicles (>17 mm in diameter) on the day of HCG injection in the rhFSH group. The number of oocytes, mature oocytes and good quality zygotes and embryos obtained were significantly increased in the rhFSH group. It is concluded that in IVF patients undergoing pituitary desensitization with a depot agonist preparation, supplemental LH may be required in terms of treatment duration and gonadotrophin consumption. However, both oocyte, embryo yield and quality were significantly higher with the use of rhFSH.     

Sequential use of letrozole and gonadotrophin in women with poor ovarian reserve: a randomized controlled trial

Sequential use of letrozole and human menopausal gonadotrophin (HMG) was compared with HMG only in poor ovarian responders undergoing IVF. Patients (n = 53) with less than four oocytes retrieved in previous IVF cycles or less than five antral follicles were randomized to either letrozole for 5 days followed by HMG or HMG alone. The letrozole group had lower dosage of HMG (P < 0.001), shorter duration of HMG (P < 0.001) and fewer oocytes (P = 0.001) when compared with controls. Live-birth rate was comparable with a lower miscarriage rate in the letrozole group (P = 0.038). Serum FSH concentrations were comparable in both groups except on day 8, while oestradiol concentrations were all lower in the letrozole group from day 4 (all P < 0.001). Follicular fluid concentrations of testosterone, androstenedione, FSH and anti-Müllerian hormone were higher in the letrozole group (P = 0.009, P = 0.001, P = 0.046 and P = 0.034, respectively). Compared with HMG alone, sequential use of letrozole and HMG in poor responders resulted in significantly lower total dosage and shorter duration of HMG, a comparable live-birth rate, a significantly lower miscarriage rate and a more favourable hormonal environment of follicular fluid.The management of poor ovarian responders or women with poor ovarian reserve in IVF is controversial. The use of letrozole has been studied; however, results are inconsistent. This randomized trial studied the sequential use of letrozole and gonadotrophin compared with gonadotrophin alone in poor responders undergoing IVF. The sequential use of letrozole and gonadotrophin led to a significantly lower dosage and shorter duration of gonadotrophin use, significantly fewer oocytes, comparable live-birth rate, a significantly lower miscarriage rate and a more favourable hormonal environment at a lower cost.     

Basal serum testosterone levels correlate with ovarian response but do not predict pregnancy outcome in non-PCOS women undergoing IVF

Purpose

To evaluate basal testosterone (T) levels in women undergoing in vitro fertilization (IVF) cycles and examine the association between basal T levels and ovarian response or IVF pregnancy outcome.

Methods

We retrospectively analyzed 1413 infertile Chinese women undergoing their first IVF treatment at our institution’s reproductive center from March 2011 to May 2013. The basal testosterone (T) levels in women undergoing in vitro fertilization (IVF) and the relationship between basal T levels and ovarian response or IVF pregnancy outcome were determined. These patients did not have polycystic ovary syndrome (PCOS) or endometriosis, and were treated with a long luteal down-regulation protocol. Subjects were divided into 2 groups according to basal testosterone (T) levels: Group 1, basal T values <20 ng/dl (n = 473), and Group 2, basal T values >20 ng/dl (n = 940). We evaluated the association of basal T levels with ovarian response and IVF outcome in the two groups.

Results

In this study, BMI, basal follicle-stimulating hormone (FSH) levels, basal luteinizing hormone (LH) levels, antral follicle count (AFC), days of stimulation, total gonadotrophin dose, basal FSH/LH ratio, and the number of follicles >14 mm were significantly different (P < 0.05) between the two groups. Basal T level positively correlated with ovarian reserve function, number of follicles >14 mm on human chorionic gonadotrophin (HCG) day, and total gonadotropin dose. However, basal T levels play no role in predicting IVF pregnancy outcome.

Conclusion

Basal T level can be used as a good predictor for ovarian response and the number of large follicles on HCG day. Additionally, we may use basal T level as a marker to predict FSH dosage. In general women, lower level of T might relate with potential poor ovarian response. However, based on our data, basal T levels do not predict pregnancy outcome.     

FSH: what is the highest dose for ovarian stimulation that makes sense on an evidence-based level?

The widely applied practice of a gonadotrophin dose increase in case of low response is not on an evidence-based level and not efficacious. All known comparative studies failed to show a difference in favour of the high-dose group regarding their pregnancy rate per embryo transfer. However if more oocytes and more embryos are available for cryopreservation, the real benefit in terms of cumulative pregnancy outcome might be with the high-dose regimen. This publication will show - as a review of the literature - that the frequent clinical practice of increasing the FSH dose does not lead to a higher pregnancy rate, which is in line with recommendation for milder stimulation regimes in IVF. Thus, the collective evidence to date would suggest that 150 IU/day to 250 IU/day of FSH or human menopausal gonadotrophin (HMG) is an appropriate starting dose for most women undergoing ovarian hyperstimulation for IVF as part of a gonadotrophin-releasing hormone (GnRH) antagonist or a long GnRH agonist protocol.     

Drug-free in-vitro activation of follicles and fresh tissue autotransplantation as a therapeutic option in patients with primary ovarian insufficiency

Research questionCould in-vitro action of follicles and fresh tissue autotransplantation without tissue culture (drug-free IVA) be useful in patients with primary ovarian insufficiency (POI)?DesignProspective observational cohort study in a tertiary university hospital. Drug-Free IVA was carried out in 14 women with POI with a median age of 33 years (29–36 years), median length of amenorrhoea of 1.5 years (1–11 years), median FSH levels 69.2 mIU/ml (36.9–82.8 mIU/ml) and anti-Müllerian hormone of 0.02 ng/ml (0.01–0.1 ng/ml). The surgical procedure included laparoscopic removal of ovarian cortex, fragmentation of tissue and autografting. Human menopausal gonadotrophin (HMG) was started immediately after surgery.ResultsFollicle development was detected in seven out of the 14 patients, and five women achieved successful oocyte retrieval. In six women, HCG was administered in 10 cycles. Six embryo transfers were carried out in five women resulting in four pregnancies; a clinical pregnancy rate of four in seven oocyte retrievals and four in six embryo transfers.ConclusionsDrug-free IVA could be a useful therapeutic option for patients with POI, leading to successful IVF outcomes.     

Superovulation strategy before in vitro fertilization

This chapter reviews current understanding of the control of spontaneous preovulatory follicular development in the natural ovarian cycle as a basis for the design and use of superovulation strategy before clinical IVF. The principles, limitations and practical aims of therapy using clomiphene citrate and HMG to stimulate multiple follicular development are outlined together with details of methods in current use to monitor ovarian response to these drugs and to time ovulation induction and egg collection with HCG. Examples of successful IVF treatment cycles are given. It is stressed that properly controlled clinical trials to judge the relative merits of the various superovulation methods in current use for IVF have not been undertaken. Possible new approaches to ovarian stimulation before IVF include the use of 'pure' FSH, LHRH and pulsatile gonadotrophin administration.     

Supplementation with human menopausal gonadotropin in the gonadotropin-releasing hormone antagonist cycles of women with high AMH: Pregnancy outcomes and serial hormone levels

ObjectiveTo evaluate the value of using both HMG and recombinant FSH (r-FSH) in the GnRH antagonist protocol for women with high AMH.Materials and methodsThis retrospective, single-center cohort study was conducted from January 2013 to December 2018. Of 277 GnRH antagonist IVF/ICSI cycles in women with anti-Mullerian hormone (AMH) ≥5 μg/L, 170 cycles receiving the combination of r-FSH and HMG (77 with HMG added at the beginning of the GnRH antagonist cycle and 93 with HMG added after GnRH antagonist administration) and 107 cycles receiving r-FSH alone were analyzed. The dynamic hormone profiles and embryonic and clinical outcomes of the patients were evaluated.ResultsWe observed significantly lower serum LH levels in the r-FSH + HMG groups during ovarian stimulation. The serum estradiol and progesterone levels were lower in the r-FSH + HMG groups on the trigger day. Nevertheless, there were no significant differences with respect to the number of oocytes retrieved, maturation, fertilization, blastocyst formation rate or ovarian hyperstimulation syndrome (OHSS). The implantation and live birth rates were increased in the r-FSH + HMG groups compared with the r-FSH alone group, with no statistical significance.ConclusionsHMG for LH supplementation in the GnRH antagonist protocol for patients with high AMH is not significantly superior to r-FSH alone in terms of ovarian response and pregnancy outcome. Nevertheless, HMG supplementation might be appropriate for women with an initially inadequate response to r-FSH or intracycle LH deficiency.     

人工授精周期中诱发排卵方法选择

在人工授精周期促排卵治疗时,为了减少卵巢的过度刺激,降低多胎妊娠发生率,必须进行卵巢微刺激的控制性促排卵方案,主要通过控制早卵泡期的启动数及优势卵泡的排卵数来完成。氯米芬、来曲唑是一线方案,人绝经期促性腺激素（HMG）或卵泡刺激素（FSH）低剂量渐增方案是比较容易达到控制目的的方案。在促排卵周期中,监测自发性黄体生成激素（LH）峰形成后产生的级联效应,可以获得最佳妊娠率。注射人绒毛膜促性腺激素（HCG）扳机后36h完成人工授精手术可能是最佳时机。     

Clomiphene citrate and ovulation induction

Clomiphene can be used to treat anovulation due to hypothalamus or pituitary gland dysfunction, and it normalizes the luteal phase in stimulated patients. It can be used to estimate ovarian follicle reserve, and may be predictive of ovulation in women aged >/=35 years or with failed IVF. Contraindications include risk of congenital anomalies, chronic liver disease and visual disorders. Clomiphene may impair fertility through its effects on cervical mucus and in causing various endometrial dysfunctions. However, if clomiphene is administered in 50 mg doses, side-effects are avoided and efficacy is similar to that of a 100 mg dose, although daily dosages of 200 mg/day over 5 days can induce ovulation in approximately 70% of treated patients. Gonadotrophin concentrations increase up to days 5-9 when follicles are selected, and clomiphene is effective in patients with polycystic ovary syndrome (PCOS). Fifty percent of normal patients conceive, a value perhaps biased by the antagonistic effects of clomiphene on cervical mucus in some women. Clomiphene is valuable for IVF, and is used by some clinics in combination with HMG or recombinant FSH. Resistance to clomiphene can develop, and human chorionic gonadotrophin may be needed to induce ovulation in clomiphene cycles. Corticosteroids and human menopausal gonadotrophin (HMG) can be combined with clomiphene for stimulation, its combination with HMG long having been a standard protocol in assisted reproduction. PCOS patients may become insulin resistant, a condition improved by the administration of metformin. Other adverse effects include multiple pregnancies, an increase in the rate of multiple births, ovarian hyperstimulation and unsubstantiated claims of ovarian cancer.     

Effects of ovulation induction agents on ovarian surface epithelium in rats

The aim of this study was to examine the effects of ovulation induction agents on the ovarian surface epithelium in rats. Sixty adult females were randomly divided into six groups, each containing 10 rats. In four of these groups ovulation induction was applied with six cycles of clomiphene citrate, human menopausal gonadotrophin (HMG), recombinant FSH (rFSH) or human chorionic gonadotrophin (HCG), respectively, followed by unilateral oophorectomy, and another six cycles of the same treatment. After a total of 12 cycles of ovulation induction, the remaining ovary was taken out and the alterations in ovarian surface epithelium were examined. No malignancies were observed on the ovarian surface epithelium of the rats that were given clomiphene citrate, rFSH or HMG as ovulation induction agents, while identification rates of histopathological parameters constituting epithelial dysplasia were found to be significant (P < 0.05). There was no significant dysplasia in the epithelium of the group which was given HCG only, relative to control groups. The findings suggest that the ovulation induction agents except for HCG bring about dysplasia in the ovarian surface epithelium. It is not clear whether these dysplasias are precursory lesions of ovarian malignancies.     

Are follicle stimulating hormone measurements predictive of ovarian response to hyperstimulation with human menopausal gonadotrophin?

Previous studies have suggested that elevated serum follicle stimulating hormone (FSH) concentrations are associated with a poor ovarian response to hyperstimulation with human menopausal gonadotrophin (HMG) in in vitro fertilisation (IVF) programmes. We have used the day 2 serum FSH concentration to determine the dose of HMG administered in women under 40 years. If the FSH concentration was below 9 IU/l, a constant dose of 150 IU HMG were administered; if above 9 IU/l a constant dose of 300 IU HMG was used. Women over the age of 40 years were given 300 IU HMG regardless of their serum FSH concentration. This retrospective study was undertaken to assess whether this approach was beneficial for the younger women and also whether the FSH concentration was predictive of outcome in older women. The study included all women < 40 years (n = 143) and > 40 years (n = 32) having their first IVF treatment cycle during 1994. In the younger women, there was no difference in the number of cancelled treatment cycles (9.7% vs. 7.5%); the number of follicles present (9.6 vs. 8.2); serum oestradiol concentration (6971 pmol/l vs. 6686 pmol/l); number of eggs collected (7.9 vs. 5.7); number of embryos created (3.7 vs. 3.6); and pregnancy rate (13.5% vs. 15%) between women with normal (n = 103) or elevated (n =40) FSH concentrations. By using the serum FSH concentration to select women in whom a poor response was expected, and administering a higher dose of HMG, a similar ovarian response was produced and the pregnancy rate was similar to those in women with normal FSH concentrations. Women over 40 years with elevated serum FSH concentrations (n = 17) had a significantly (P < 0.05) higher cancellation rate (17.6% vs. 0%) and fewer number of eggs collected (6.9 vs. 2.5) than the group with normal FSH concentrations (n = 15). One woman conceived in each group. These findings confirmed previous studies showing that the serum FSH is predictive of ovarian response. This study confirmed the value of measuring the day 2 serum FSH concentration as a predictor of response; and it provides a scientific approach to determine the dose of HMG administered for IVF stimulation. A satisfactory response to induction of ovulation will be achieved using 150 IU HMG in women with FSH < 9 IU/l but if the FSH is raised i.e. above 9 IU/l, 300 IU is required to achieve a similar response.