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PubMed1998

Sequential clomiphene citrate and human menopausal gonadotrophin with intrauterine insemination: the effect of patient age on clinical outcome.

The purpose of this investigation was to examine the influence of female and male patient age on pregnancy rates with sequential clomiphene citrate (CC) and human menopausal gonadotrophin (HMG) ovulation induction with intrauterine insemination (IUI) therapy after previous CC and IUI treatment failure. A total of 208 patients previously unable to conceive with CC/IUI therapy underwent 416 treatment cycles of sequential CC/HMG with IUI at a university fertility centre between May, 1991 and August, 1995. Clinical pregnancy rates, live birth rates, and the effect of female and male partner chronological age were retrospectively examined. Treatment with sequential CC/HMG with IUI resulted in clinical pregnancy rates ranging from 5.9 to 23.1% despite previous CC/IUI treatment failure. Clinical pregnancy rates, live birth rates, and cumulative pregnancy rates declined significantly in female patients > or = 35 years of age compared to those < 35 years of age. A statistically significant decline in clinical pregnancy rates could not be demonstrated as a function of increasing male partner age. Pregnancy rates in patients undergoing ovulation induction with sequential CC/HMG with IUI decline significantly with increasing female partner age.

Adult↗
PubMed2002

Three-dimensional assessment of ultrasound features in women with clomiphene citrate-resistant polycystic ovarian syndrome (PCOS): ovarian stromal volume does not correlate with biochemical indices.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a heterogeneous endocrine disorder affecting women of reproductive age. The syndrome is characterized by a combination of polycystic ovarian morphology, clinical features and biochemical indices. The objective of this prospective observational study was to investigate the relationship between the total ovarian volume and the ovarian stromal volume, measured using a three-dimensional (3D) ultrasound scan, with biochemical indices of PCOS. METHODS: Twenty-three infertile women (mean age +/- SD: 31 +/- 3.1 years; range: 26-37) with clomiphene citrate-resistant PCOS were examined. Early follicular phase (days 2-4) serum FSH, LH and testosterone concentrations were measured following a withdrawal bleed. Total ovarian volume, stromal volume, pre-antral follicle (<10 mm) number and total follicular volume were measured by 3D transvaginal ultrasound. RESULTS: Total ovarian volume, follicular volume and follicle number correlated positively with serum FSH and LH, but not testosterone, concentrations. Ovarian stromal volume correlated strongly with total ovarian volume only, but not with serum FSH, LH or testosterone concentrations. CONCLUSIONS: These findings demonstrate an association of the total ovarian volume, pre-antral follicle number and total follicular volume with some of the biochemical indices of PCOS, but no association was observed between ovarian stromal volume and these indices.

Adult↗
PubMed2002

Ovarian stimulation in intrauterine insemination with donor sperm: a randomized study comparing clomiphene citrate in fixed protocol versus highly purified urinary FSH.

BACKGROUND: The study was conducted to compare the results of intrauterine donor insemination (DI) under ovarian stimulation with either clomiphene citrate (CC), in a fixed protocol, or FSH, with ovarian monitoring. METHODS: Forty-nine patients were randomized using a computer-generated list to receive highly purified urinary FSH (starting dose of 150 IU) and were subjected to periodic vaginal ultrasound and estradiol determinations. HCG was given when > or =2 follicles (> or =17 mm) were identified and estradiol reached >400 pg/ml. Intrauterine insemination (IUI) was performed 36 h later. The other 51 received CC on a fixed protocol (100 mg/day from the day 5-10 of the ovarian cycle) with HCG being administered on the day 12, and IUI performed 36 h later. Up to six IUI cycles were performed on all patients if pregnancy was not reached before. Women failing to conceive in the CC group underwent IUI with FSH. The main outcome measures were intrauterine gestational sac observed by transvaginal ultrasound, per cycle and per woman pregnancy rate (PR) and multiple PR. RESULTS: The per cycle PR was significantly higher in the FSH group, 14.4% (30/209) versus 6.1% (16/261), as well as the per woman PR, 61.2% (30/49) versus 31.4% (16/51). 12.5% (2/16) of pregnancies obtained in the CC group were multiple, compared with 20% (6/30) in the FSH group. There were no triplets or higher order pregnancies in CC versus two in FSH (6.7% of pregnancies). Patients failing to conceive with CC, who later underwent intrauterine DI with FSH, had similar results to the primary FSH group: 54.3% PR per patient (19/35) and 16.0% per cycle (19/118), with a multiple PR of 31.6% (6/19). The PR for women starting with CC cycles and, if pregnancy was not obtained, continuing with six FSH cycles, was 69.2%. CONCLUSIONS: The PR obtained with CC stimulation was approximately half that obtained with FSH. There was a trend to lower multiple PR with CC. It is recommended that each case should be considered on an individual basis and the treatment options discussed with patients. In our opinion, CC could be a reasonable approach for young women with good prognosis, whereas in the remaining cases FSH would be the preferable method.

Adult↗
PubMed2003

Ovarian stimulation by clomiphene citrate and hMG in combination with cetrorelix acetate for ICSI cycles.

BACKGROUND: The introduction of GnRH antagonists such as cetrorelix acetate has made possible the simplification of ovarian stimulation. However, the most effective protocol for their administration has not yet been clearly defined. METHODS: Forty women with male-factor infertility undergoing 40 ICSI cycles were included in the study. Clomiphene citrate at 100 mg a day was given from cycle day 3 through day 7. hMG at 150 IU was given on cycle days 4, 6 and 8, and was adjusted from day 9 according to the follicular and hormone responses. Cetrorelix acetate at 2.5 mg was administered when the leading follicle reached 14 mm. The remaining 0.5 mg was divided into two 0.25 mg injections for possible later use. Serum FSH, LH, estradiol and progesterone levels were measured daily from the day of cetrorelix acetate injection until hCG was given. RESULTS: Serum LH level was suppressed effectively for 4 days. Four patients (10%) needed one or two additional injections of 0.25 mg cetrorelix acetate. No premature LH surge was detected in any of the women treated. Sixteen women became pregnant (40%), of which 14 pregnancies (35%) were ongoing at the time of writing. CONCLUSIONS: This study demonstrates that this new protocol is feasible for couples with male-factor infertility undergoing ICSI.

Adult↗
PubMed2003

Undescended ovary and unicornuate uterus: simplified diagnosis by the use of clomiphene citrate ovarian stimulation and magnetic resonance imaging (MRI).

BACKGROUND: Although the association between unicornuate uterus and undescended ovaries is well established, little information is available on this entity, suggesting the possibility that many cases are not recognized at all. Consequently, important clinical information is missed in many patients worldwide. METHODS: During a period of 5 years, eight cases of unicornuate uterus were observed in our infertility clinic. The first three patients received magnetic resonance imaging (MRI) after mild clomiphene citrate (CC) stimulation due to a discrepancy between estradiol levels and follicular growth and because a suspected ectopic ovary could not be visualized on ultrasound. Based on this experience, five consecutive patients were offered MRI after CC stimulation as part of this study. RESULTS: In five out of eight patients with unicornuate uterus (62.5%) an undescended ovary could be visualized in the upper abdomen. Abdominal ultrasound revealed the ectopic ovary in only two cases. The use of CC stimulation undoubtedly facilitated the diagnosis of the undescended ovary on MRI. CONCLUSION: It is suggested that MRI after CC stimulation is an excellent non-invasive method to diagnose undescended ovaries in women with a unicornate uterus.

Adult↗
PubMed2004

Laparoscopic electrocautery of the ovaries versus recombinant FSH in clomiphene citrate-resistant polycystic ovary syndrome. Impact on women's health-related quality of life.

BACKGROUND: Ovulation induction with gonadotrophins is the standard treatment strategy for women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). Laparoscopic electrocautery of the ovaries is an alternative treatment modality, leading to a comparable cumulative pregnancy rate. In deciding which treatment to opt for, women's health-related quality of life (HRQoL) should be taken into account. METHODS: A total of 168 CC-resistant women with PCOS were randomly assigned to receive either the electrocautery strategy, entailing laparoscopic electrocautery of the ovaries followed by CC and recombinant FSH (rFSH) if anovulation persisted, or ovulation induction with rFSH. We assessed women's HRQoL with the standard questionnaires Short Form-36, Rotterdam Symptom Checklist and Center for Epidemiological Studies Depression Scale, administered before randomization and 2, 12 and 24 weeks thereafter. RESULTS: The intention to treat analysis revealed no significant differences between the treatment groups on any of the scales at any point during follow-up. In women without an ongoing pregnancy, those treated with rFSH showed significantly more depressive symptoms than women allocated to the electrocautery strategy, with or without CC, although differences were small. CONCLUSIONS: Overall, HRQoL was not affected in both groups. In women still under treatment, rFSH was slightly more burdensome for women's HRQoL than electrocautery with or without CC.

Clomiphene↗
PubMed2004

Repeated clomiphene citrate challenge testing in the prediction of outcome in IVF: a comparison with basal markers for ovarian reserve.

BACKGROUND: The aim of this study was to investigate the predictive accuracy and clinical value of performing either a single or a repeated clomiphene citrate challenge test (CCCT) in predicting poor response in IVF, compared to that of currently used basal ovarian reserve markers. METHODS: Sixty-three patients undergoing their first IVF treatment were prospectively included. After measurement of basal markers on cycle day 3 (cd3) [FSH, inhibin B and antral follicle count (AFC)], a CCCT was performed. FSH and inhibin B levels were measured on day 10 (cd10). A second CCCT was performed after a washout period of one cycle. In all patients the tests were followed by an IVF treatment. Poor response (<4 oocytes or cancellation due to impaired (<3 follicles) or absent follicular growth) was used as primary outcome measure. RESULTS: Both the single as well as the repeated CCCT markers had a rather good discriminative potential for the prediction of poor response (area under the receiver operating characteristic curve (ROCAUC): FSH cd10=0.79, inhibin B cd10=0.79, mean FSH cd10=0.82 and mean inhibin B cd10=0.88). This compared well with the performance of the basal markers (FSH 0.82, inhibin B 0.72 and AFC 0.83). In a multivariate analysis on only the basal variables, FSH cd3 and AFC were selected (ROCAUC 0.89). Only stepwise forward analysis on the repeated CCCT variables revealed a better discriminating potential for the prediction of poor response (ROCAUC 0.92). At a specificity level of approximately 0.97, sensitivity and the positive predictive value were marginally improved in the CCCT models. CONCLUSIONS: Performing a CCCT (single or repeated) has a rather good ability to predict poor response in IVF. However, it appears that the predictive accuracy and clinical value of the CCCT is not clearly better than that of basal FSH in combination with an AFC. Therefore, the use of the CCCT as a predictor of outcome in IVF should not be advocated.

Adult↗
PubMed2005

Predictors for treatment failure after laparoscopic electrocautery of the ovaries in women with clomiphene citrate resistant polycystic ovary syndrome.

BACKGROUND: Laparoscopic electrocautery has been put forward as the treatment of choice in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). In order to make an informed treatment decision it would be helpful if we could identify women with PCOS with a high probability of treatment failure following electrocautery of the ovaries. METHODS: Eighty-three women with CC-resistant PCOS were allocated to receive laparoscopic electrocautery followed by CC when anovulation persisted as part of a randomized controlled trial. Multivariable logistic regression analyses using clinical, ultrasonographic and endocrinological parameters were performed to predict (i) failure to ovulate within 8 weeks after electrocautery, and (ii) failure to reach an ongoing pregnancy after electrocautery with or without CC. RESULTS: Of the 83 women, 56 (67%) ovulated within 8 weeks after electrocautery. The model for predicting anovulation after electrocautery included LH/FSH rate, year of menarche and glucose level. Women who were younger at menarche, had a lower LH/FSH ratio and a lower glucose level were more likely to have persistent anovulation. The area under the curve was 0.74. After electrocautery and CC, 41 women reached an ongoing pregnancy. No prognostic parameters could be identified to predict failure to reach an ongoing pregnancy after electrocautery followed by CC. CONCLUSIONS: Persistence of anovulation after electrocautery could be predicted and women with a high risk of persisting anovulation could be distinguished. We were, however, not able to predict treatment failure after electrocautery followed by CC.

Adult↗
PubMed2005

Antral follicle count and FSH concentration after clomiphene citrate challenge test in the prediction of ovarian response during IVF treatment.

BACKGROUND: We compared: (i) antral follicle count (AFC) in the early follicular phase, after the clomiphene citrate challenge test (CCCT) and before ovarian stimulation following pituitary down-regulation; and (ii) age of women, body mass index, basal and stimulated serum FSH concentrations and AFC in predicting the ovarian response of infertile women aged <40 years with basal FSH <10 IU/l on recruitment in their first IVF cycle. METHODS: Two months prior to the treatment cycle, AFC and basal FSH concentration were determined on day 2-3 of a spontaneous period and on day 10 after CCCT. All women received a standard stimulation regimen. Ovarian response was represented by the number of oocytes, serum estradiol, the duration and dosage of gonadotrophins. RESULTS: There was no significant difference between basal, stimulated and down-regulated AFC. AFC achieved the best predictive value in relation to the number of oocytes, followed by combined FSH concentration (sum of the two FSH concentrations) and age of women. Both basal AFC and combined FSH concentration were predictive factors of serum estradiol concentration, whereas stimulated FSH concentration was predictive of the total dosage of gonadotrophins. CONCLUSION: Combined FSH concentration after CCCT provides additional information in predicting ovarian response.

Adult↗
PubMed2005

Clomiphene citrate--end of an era? A mini-review.

The purpose of this review is to examine whether the time has come to replace clomiphene citrate (CC) as the first line therapy for WHO group II (eu-oestrogenic) infertility, the majority of which is associated with polycystic ovary syndrome. CC has been the first line therapy for these cases for the last 40 years. It is a simple, cheap treatment, almost devoid of side effects which yields a single live birth rate of approximately 25% of starters. Non-response to CC and the gap between ovulation and pregnancy rates have variously been attributed to its anti-estrogen effects, and high LH and androgen concentrations. Three possible contenders for the replacement of CC as first-line treatment are scrutinized: metformin, aromatase inhibitors and low-dose FSH. Each has their advantages and disadvantages, but none of them, while showing much potential promise, has been proven, as yet, to be a feasible replacement for CC in this role. For CC, it may not yet be the end of an era but it may be the beginning of the end.

Clomiphene↗
PubMed2006

A randomized clinical trial of clomiphene citrate versus low dose recombinant FSH for ovarian hyperstimulation in intrauterine insemination cycles for unexplained and male subfertility.

BACKGROUND: Controlled ovarian hyperstimulation with intrauterine insemination (IUI) is a widely accepted treatment for unexplained and male subfertility. No consensus exists about the drug of first choice to be used as hyperstimulation. This randomized multicentre trial using a parallel design compares the efficacy of clomiphene citrate (CC) with that of recombinant FSH (rFSH). METHODS: Couples with primary unexplained or male subfertility were randomized to receive CC or rFSH for ovarian hyperstimulation. The treatment was continued for up to four cycles unless pregnancy occurred. Cycles with more than three follicles were cancelled. Cumulative pregnancy rates and live birth rates were primary outcomes. Cancellation during treatment and multiple birth rates are secondary outcomes. Results were analysed following the intention-to-treat principle. RESULTS: Seventy couples with male subfertility and 68 couples with unexplained subfertility were included. Seventy-one women received CC, and 67 received rFSH. Twenty-seven pregnancies were observed in the CC group (38%) and 23 in the rFSH group (34.3%) relative risk (RR) 1.11 [95% confidence interval (95% CI) 0.71-1.73]. The live birth rate was 28.2% (20/71) and 26.9% (18/67) for CC and rFSH, respectively, RR 1.05 (95% CI 0.61-1.80). Overall, the live birth rates per cycle were 10% for CC-stimulated and 8.7% for rFSH stimulated cycles. The total multiple pregnancy rate was 6.0%. Thirty-five cycles (8.6%) were cancelled because of four or more follicles (CC, n = 17; rFSH, n = 18). CONCLUSIONS: In couples with primary unexplained or male subfertility participating in an IUI program, ovarian hyperstimulation can be achieved by CC or rFSH. No significant difference in live birth rates between CC and rFSH was observed. Being less expensive, CC seems the more cost-effective drug and therefore, can be offered as drug of first choice.

Adult↗
PubMed1996

Long-term evaluation of implantation of fresh and cryopreserved human embryos following ovarian stimulation with buserelin acetate-human menopausal gonadotrophin (HMG) or clomiphene citrate-HMG.

This study is a long-term evaluation of the total pregnancy potential of cohorts of fresh and cryopreserved sibling embryos from in-vitro fertilization (IVF) cycles stimulated with either the gonadotrophin-releasing hormone analogue buserelin (BUS) (long protocol) or clomiphene citrate (CC) both in combination with human menopausal gonadotrophin (HMG). Therefore a retrospective analysis was performed on patients who entered the IVF programme between January 1986 and July 1987 and who had triple embryo transfer in the collection cycle. Significantly more fertilized oocytes developed to good-quality embryos in the CC-HMG group (86.1%) than in the BUS-HMG group (80.8%). Transfer of the three morphologically best-looking embryos was performed in day 2 post-insemination in 106 CC-HMG and 80 BUS-HMG cycles. Supernumerary embryos were cultured for a further 24 h and multicellular embryos with up to 20% of fragments were frozen slowly with 1.5 M dimethylsulphoxide on day 3 post-insemination (162 embryos in CC-HMG cycles, 102 embryos in BUS- HMG cycles). Outcome was measured by embryo survival rate, embryo implantation rate and delivery rate in fresh and frozen embryo transfers. Delivery rates were 31.3 and 21.7% per fresh embryo transfer in BUS-HMG and CC- HMG cycles respectively. Fresh embryo implantation rates were significantly higher in collection cycles stimulated with BUS-HMG (17.9%) than in cycles stimulated with CC-HMG (11.3%). Implantation rates were significantly enhanced in embryos transferred in excess of one in cycles leading to pregnancy, perhaps indicative of higher embryo quality in BUS-HMG cycles. Almost all cryopreserved embryos have by now been thawed, so the contribution of frozen embryos to overall pregnancy rates can be evaluated. Overall morphological survival rates of frozen-thawed embryos have by now been thawed, so the contribution of frozen embryos to overall pregnancy rates can be evaluated Overall morphological survival rates of frozen-thawed embryos were similar for 140 embryos from CC-HMG cycles (50%) and 100 embryos from BUS-HMG cycles (46%). The percentage of fully intact embryos was, however, significantly lower in the BUS-HMG group (19%) than in the CC-HMG group (39.5%). Delivery rates were significantly lower following 30 transfers of frozen-thawed embryos from BUS-HMG-stimulated cycles (3.3%) than following 42 transfers of frozen-thawed embryos from CC-HMG cycles (19.1%). Embryo implantation rates were lower for frozen-thawed embryos from BUS-HMG cycles (2.3%) than from CC-HMG cycles (12.7%). Here we demonstrate that ovarian stimulation with the long protocol BUS-HMG instead of the CC-HMG protocol led to higher embryo implantation rates in collection cycles but to lower intact embryo survival rates and to lower embryo implantation rates for frozen sibling embryos. Despite the lower implantation rates with frozen embryos originating from the BUS-HMG protocol, there was no significant difference between total delivery rate per transfer from cycles stimulated with CC-HMG (30.2%) compared with BUS-HMG (33.8%).

Adult↗
PubMed1996

Late luteal phase dydrogesterone in combination with clomiphene or tamoxifen in the treatment of infertility associated with irregular and infrequent menstruation: enhancing patient compliance.

This pilot study was undertaken to determine whether dydrogesterone administered in the late luteal phase might have a potential benefit for infertility associated with irregular and infrequent menstruation. Between April 1994 and February 1995, 54 normo-prolactinaemic women received either tamoxifen, if there was evidence of polycystic ovaries and/or increased luteinizing hormone (LH) secretion, or clomiphene together with dydrogesterone 10 mg twice daily on days 21-26 of the menstrual cycle. A total of 23 women (42.6%) conceived (10.7% per cycle). In 192 non-conception cycles the average cycle length was 29.6 days; 182 cycles (94.8%) were 34 days or less. Patients found the rapid onset of regular menstruation to be encouraging and compliance was excellent. Controlled studies are indicated to determine whether the addition of dydrogesterone to oral ovarian stimulation is beneficial.

Adult↗
PubMed1996

Combined intra-uterine and extra-uterine pregnancy associated with mild hyperstimulation syndrome after clomiphene ovulation induction.

We report a combined intra-uterine and tubal pregnancy associated with mild ovarian hyperstimulation syndrome (OHSS) following ovulation induction by clomiphene. The diagnosis of ectopic pregnancy was originally missed until rupture occurred. OHSS confused the clinical picture, the important diagnostic feature being the fall in the haemoglobin concentration. The patient had a left partial salpingectomy and the uterine pregnancy progresses normally.

Adult↗
PubMed1987

Monitoring of clomiphene citrate stimulation by means of plasma 17 beta-oestradiol determinations and ultrasonographic follicle measurements in in-vitro fertilization treatment cycles.

In 57 in-vitro fertilization (IVF) cycles stimulated with clomiphene citrate the relationship between plasma 17 beta-oestradiol (E2) and ultrasonographic measurements of follicle diameter was assessed. Under both monofollicular and multifollicular conditions a wide range in plasma E2 values was observed in the late follicular phase. No significant correlation could be established between the dimensions of the dominant preovulatory follicle and plasma E2 values, in mono-follicular or multi-follicular cycles. Pregnancies and conceptions occurred in cycles with both low and high circulating E2 levels. In pregnancy cycles a slight increase in plasma E2 values was found on the day following administration of human chorionic gonadotrophin (HCG). In conceptional cycles not leading to a clinical pregnancy, plasma E2 profiles varied considerably, whereas in cycles in which no oocytes were fertilized, plateauing or a distinct decrease occurred during this particular period. The present study suggests that the relative daily increase in plasma E2 values may be the most relevant aspect of plasma E2 monitoring.

Clomiphene↗
PubMed1989

Low multiple pregnancy rate in combined clomiphene citrate--human menopausal gonadotrophin treatment for ovulation induction or enhancement.

Sixty-five infertile women, 37 with anovulation, eight with ovulatory disturbances and 20 with unexplained infertility were treated by a combination of clomiphene citrate (CC) from cycle day 5 (or 3) and human menopausal gonadotrophin (HMG) begun 3 days later for induction or enhancement of ovulation. Monitoring was carried out by measuring preovulatory 17-beta-oestradiol (E2) and progesterone (P) concentrations in blood samples and by follicle measurements using ultrasound. Forty-seven pregnancies resulted with a multiple pregnancy rate of 7.7% for those completed. This incidence is very low and within the range found for CC induction and might result from the later commencement of stimulation compared with many other protocols. These results were achieved with a low incidence of ovarian hyperstimulation syndrome (2.6% per cycle). The HMG doses given were low in comparison with those found in other forms of induction. The deleterious effects of this combined mode of induction on cervical mucus and the occurrence of premature spontaneous ovulation were much less than in the sequential mode of treatment. These results suggest that combined induction treatment by CC and HMG as described offers a means of achieving low rates of multiple pregnancies a known complication in the induction of ovulation.

Adult↗
PubMed1989

Follicle-stimulating hormone as a prognostic indicator in clomiphene citrate/human menopausal gonadotrophin-stimulated cycles for in-vitro fertilization.

Follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol and prolactin levels were studied in a sequential clomiphene citrate/human menopausal gonadotrophin (CC/HMG) regimen for in-vitro fertilization. At completion of CC administration, the median FSH level in 44 cancelled cycles was elevated compared to a control group of 65 completed cycles, 29 IU/l versus 15 IU/l, P less than 0.01. Also the median FSH/LH ratio was higher in the cancelled cycles than in the control group, 1.08 versus 0.71, P less than 0.05. Conversely, the median oestradiol level was lower in the cancelled cycles than in the completed cycles, 0.27 nmol/l versus 0.59 nmol/l, P less than 0.01. No difference was seen in the median LH and prolactin levels. An FSH value above the 95% confidence limit was found in 24 of the cancelled cycles, but in only two of the completed cycles. Based on this study, an elevated FSH value following CC administration predicts a poor response to further stimulation with an accuracy of 92.3% and should result in cancellation of the cycle.

Adult↗
PubMed1990

Effect of clomiphene citrate on oestrogen secretion by human granulosa cells in culture.

The effect of clomiphene citrate (CC) and 17 beta-oestradiol (E2) on oestrogen secretion was studied in human preovulatory granulosa cells in culture. CC stimulated E2 secretion at 1 and 10 ng/ml (respectively, +36 +/- 14% and +33 +/- 5%) in basal conditions but had no effect on FSH-stimulated E2 secretion. On the other hand, E2 had no effect at any of the tested concentrations (0.1 ng/ml to 1000 ng/ml) on its own production. Since the plasma level of CC obtained in clinical use ranges from 1 to 10 ng/ml, this finding could explain the higher plasma oestrogen levels obtained with CC as compared to human menopausal gonadotrophin.

Androstenedione↗