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PubMed2003

A pilot study of the use of low dose human menopausal gonadotropin in ovulation induction.

OBJECTIVE: To evaluate the clinical efficacy of a combined regimen of follicle stimulating hormone (FSH) and low dose human menopausal gonadotropin (hMG) following GnRH agonist ultralong protocol in controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET). STUDY DESIGN: IVF-ET was performed on 45 patients who had uterine or peritoneal factors, such as moderate to severe endometriosis, adenomyosis, or uterine myoma. The patients were randomized into two groups after the administration of long-acting GnRH agonist 2-4 times within a 4-week interval; highly purified FSH (FSH-HP) and hMG (Group A, n=26), FSH-HP only (Group B, n=19). hMG was administered at a fixed-dose of 75IU per day and the dose of FSH-HP was adjusted according to the patient's individual response. The results of COH and IVF-ET were assessed and compared between the two groups. RESULTS: Serum estradiol (E2) level on hCG day was significantly higher in Group A (1418.2+/-920.2 pg/ml, mean+/-S.D.) than in Group B (678.4+/-457.8 pg/ml) (P<0.05). The clinical pregnancy rate and implantation rate tended to be higher in Group A than in Group B; 23.1% (6/26) versus 10.5% (2/19), 11.0% (9/82) versus 4.6% (3/65). CONCLUSION: In COH for IVF-ET using GnRH agonist ultralong protocol, the combined treatment of FSH-HP and low dose hMG showed a higher serum E2 level when compared with treatment with FSH-HP alone.

Adult↗
PubMed2006

The only effects of recombinant follicle-stimulating hormone for ovulation induction in the pre-implantation period of rats.

OBJECTIVE: The aim of this study was to evaluate the changes in follicular development, serum hormonal levels, and endometrium in the pre-implantation period of rats by using recombinant FSH (rFSH) without human chorionic gonadotropin (hCG). METHODS: Thirty female rats were studied in six groups of five specimens. Two groups determined as controls (groups 1 and 2). Two groups received constant doses of rFSH (groups 3 and 4) and other two decreasing doses (groups 5 and 6). One of the paired groups was mated. Uterus, ovaries, and blood samples were taken from non-mated groups (groups 1, 3, and 5) at the proestrus period and from mated groups (groups 2, 4, and 6) in the pre-implantation period. RESULTS: In non-mated groups antral follicles and corpus luteum periodicum and in mated groups antral follicles, corpus luteum periodicum, and corpus luteum graviditatis were increased in rFSH groups, especially in decreasing dose groups. Estradiol (E2) levels were increased and progesterone (P)/E2 ratio was significantly decreased in decreasing dose groups. Endometrium surface epithelium was columnar, irregular, and folded in rFSH groups. Endometrium glandular epithelium was cuboidal in all groups. In decreasing dose groups endometrial stroma was smooth and fibroblastic. Mitotic indices of endometrium surface, glandular epithelium, and stroma were significantly decreased in rFSH groups. Primary follicles and P levels showed no change. CONCLUSION: It seems likely that decreasing doses of rFSH might be used in order to improve follicular development, although it has negative effects with E2 on endometrium in the pre-implantation period of rats.

Animals↗
PubMed1994

High ovarian response in Yoruba African women during ovulation induction for assisted conception.

Fertile Yoruba women from western Nigeria have a much higher incidence of naturally conceived multizygotic twin and triplet pregnancies than Caucasians. The objective of the present study was to determine whether there are differences between infertile Yoruba and Caucasian women in terms of ovarian response in stimulate cycles for assisted conception. A total of 11 Yoruba women were scheduled for 14 in-vitro fertilization (IVF) and one gamete intra-Fallopian transfer (GIFT) cycles from 1990 to 1992. The Caucasian group consisted of 209 women scheduled for 213 IVF and 22 GIFT cycles during the same period. Buserelin, 500 micrograms subcutaneously daily, was started in the mid-luteal phase to achieve pituitary desensitization. Ovarian stimulation was with variable amounts of menopausal gonadotrophins. Human chorionic gonadotrophin (HCG) was given to trigger the ovulatory process. The Yoruba and Caucasian groups were similar in age and body weight, but significantly more Yorubas (45 versus 11%; P < 0.005) had ultrasound features of polycystic ovary syndrome (PCOS). The serum oestradiol concentration (3024 versus 2058 pg/ml; P < 0.05) and number of follicles > 14 mm in diameter (15.5 versus 9.5; P < 0.05) on the day of HCG were higher in the Yoruba group. The ovarian hyperstimulation syndrome (OHSS) was also more prevalent in the Yoruba group (20 versus 5%; P < 0.05). No difference was found in clinical pregnancy or embryo implantation rates. These results show a higher tendency toward exaggerated ovarian response in infertile Yoruba than Caucasian women, associated with a higher prevalence of PCOS. The risk of developing symptomatic OHSS is higher in Yoruba women.

Embryo Implantation↗
PubMed2005

Ovulation induction in the new millennium: recombinant follicle-stimulating hormone versus human menopausal gonadotropin.

The renewed interest in luteinizing hormone (LH), together with limited and decreasing health resources, make essential the comparison of high-cost, recombinant follicle-stimulating hormone (rFSH) preparations (devoid of LH) and human menopausal gonadotropin (hMG) in terms of clinical efficacy. All published, randomized controlled trials (RCTs) comparing rFSH versus hMG under different protocols of stimulation were examined. Eight true RCTs were included in this meta-analysis, recruiting 2031 participants. Data for ongoing pregnancy/live birth rate, clinical pregnancy rate, miscarriage rate, multiple pregnancy rate and ovarian hyperstimulation syndrome (OHSS) were extracted, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with the use of a fixed-effects model. Data for the meta-analysis were combined using RevMan software (using the Mantel-Haenszel method). Pooling the results of these RCTs showed no significant difference between rFSH and hMG regarding the different outcomes: ongoing pregnancy/live birth rate, OR 1.18 (95% CI 0.93-1.50); clinical pregnancy rate, OR 1.2 (95% CI 0.99-1.47), miscarriage rate, OR 1.2 (95% CI 0.70-2.16); multiple pregnancy rate, OR 1.35 (95% CI 0.96-1.90); incidence of moderate/severe OHSS, OR 1.79 (95% CI 0.74-4.33). However, there was significant reduction in the amount of gonadotropins in favor of hMG over rFSH. There was no significant heterogeneity of treatment effect across the trials. In conclusion, there is no clinically significant difference between hMG and rFSH in in vitro fertilization/intracytoplasmic sperm injection cycles. Decision-makers should establish their choice of one drug over the other based on the most up-to-date evidence available.

Adult↗
PubMed2005

Individualized cost-effective conventional ovulation induction treatment in normogonadotrophic anovulatory infertility (WHO group 2).

BACKGROUND: Conventional treatment in normogonadotrophic anovulatory infertility (WHO 2) consists of clomiphene citrate (CC), followed by exogenous gonadotrophins (FSH) and IVF. Response to these treatments may be predicted on the basis of individual patient characteristics. We aimed to devise a patient-tailored, cost-effective treatment algorithm involving the above-mentioned treatment modalities, based on individual patient characteristics. METHODS: Sixteen prognostic groups are defined, according to the presence or absence of: age >30 years, amenorrhea, elevated androgen levels and obesity. The chances of response with each of the three treatments were calculated using prediction models. Treatment costs were based on the data of 240 patients visiting a specialist academic fertility unit. Outcome was an ongoing pregnancy within 12 months after initiation of treatment. The costs per pregnancy of three different strategies were compared, with a threshold for cost-effectiveness of 10 000. RESULTS: The strategy CC + FSH + IVF compared with FSH + IVF generated more pregnancies against lower costs. Compared with CC + IVF, it also produced more pregnancies, but at higher costs. For <30 years of age with normal androgen levels, costs per pregnancy were less than 10 000. For women >30 years old, costs per pregnancy were 25 000 and over 200 000, when presenting with normal or elevated androgen levels, respectively. CONCLUSIONS: The conventional treatment protocol is efficient for women aged <30 years with normal androgen levels. For women >30 years old with elevated androgen levels, FSH may be skipped.

Adult↗
PubMed2000

Circulating leptin levels during ovulation induction: relation to adiposity and ovarian morphology.

OBJECTIVE: To assess serum leptin levels based on body habitus and ovarian morphology during controlled ovarian hyperstimulation. DESIGN: Prospective analysis. SETTING: University IVF program. PATIENT(S): Women undergoing IVF-ET were divided into two groups, obese ovulatory women (n = 6; mean (+/-SD) body mass index, 30.1 +/- 0.6 kg/m(2)) and lean ovulatory women (n = 20); mean (+/- SD) body mass index 22.0 +/- 0.2 kg/m(2)). Lean women were categorized further according to whether they had polycystic-appearing ovaries (n = 8) or normal-appearing ovaries (n = 12). INTERVENTION(S): Controlled ovarian hyperstimulation and IVF. MAIN OUTCOME MEASURE(S): Serum estradiol, testosterone, and leptin. RESULT(S): Mean (+/- SD) leptin levels were significantly higher before and after GnRH agonist down-regulation in obese women (41.7 +/- 5.2 pg/mL and 36.1 +/- 5.8 pg/mL, respectively) compared with lean women (8.4 +/- 1.0 pg/mL and 6.9 +/- 1.1 pg/mL, respectively). Mean (+/- SD) leptin levels increased significantly in both groups (54.5 +/- 5.1 pg/mL and 11.7 +/- 1.2 pg/mL, respectively), and the mean (+/-SD) percentage increase was similar (55% +/- 18% and 54.8% +/- 17%, respectively). Mean (+/-SD) leptin levels were similar in women with polycystic-appearing and normal-appearing ovaries before controlled ovarian hyperstimulation, but increased significantly in women with polycystic-appearing ovaries afterward (14.7 +/- 1.8 pg/mL and 9.3 +/- 1.0 pg/mL, respectively). CONCLUSION(S): Significant increases in leptin levels occur during controlled ovarian hyperstimulation, suggesting that leptin plays a role in follicular growth and maturation. The exaggerated response in women with polycystic-appearing ovaries reflects either a greater number of recruited follicles or a predisposition of adipocytes to leptin production.

Adult↗
PubMed1992

Clinical and endocrinological changes in women following ovulation induction using buserelin acetate/human menopausal gonadotrophin augmented with biosynthetic human growth hormone.

Biosynthetic human growth hormone added to an ovarian stimulation regime of human menopausal gonadotrophin (HMG) for IVF treatment improves the response of women who were previously resistant. This study investigated the efficacy of growth hormone (GH)/buserelin/HMG treatment in women with a previous normal response to buserelin/HMG stimulation. Ten patients (28-36 years, mean 32.5 years) were treated with GH (6 IU/day) plus buserelin/HMG. A control group of 10 women (28-37 years mean 31.0 years) received buserelin/HMG alone. All were given buserelin 500 micrograms and 2 ampoules (150 IU) HMG daily once pituitary suppression had been confirmed. There was no improvement in the GH group as assessed by follicular growth rate or number, oocyte number per woman and pregnancy rate. There was no effect of GH upon the serum oestradiol level and the follicular fluid levels of oestradiol, GH and inhibin. Serum IGF-1 increased significantly during GH administration, returning to pre-treatment levels 2 days after the last dose of GH. Follicular IGF-1 was much higher in the GH-treated group than the controls. Significant correlations were found in the GH-treated group between follicular fluid GH and follicular fluid oestradiol concentrations and between follicular GH and follicular size. Follicular IGF-1 was correlated with the serum IGF-1 concentration on day 8 of the GH/HMG treatment. In conclusion GH/buserelin/HMG treatment in women with a previous normal response to buserelin/HMG stimulation increased their serum and follicular IGF-1 concentrations. However, it does not improve the clinical ovarian response or the follicular secretion of oestradiol or inhibin.

Adult↗
PubMed1999

A prospective, randomized comparison of ovulation induction using highly purified follicle-stimulating hormone alone and with recombinant human luteinizing hormone in in-vitro fertilization.

The commercial availability of highly purified, s.c. administered urinary follicle stimulating hormone (FSH) preparations for ovarian stimulation marked the beginning of a new era in the treatment of infertility. As these new formulations contain essentially no luteinizing hormone (LH), supplemental LH may be needed for optimal folliculogenesis. It was the aim of this pilot study to compare fertilization rates, embryo morphology, implantation rates and pregnancy outcomes prospectively in two age-matched patient groups: women who received highly purified FSH (FSH-HP) (n = 17), and women who received FSH-HP plus recombinant human LH (rhLH, n = 14) throughout ovarian stimulation. All patients received mid-luteal pituitary down-regulation with s.c. gonadotrophin-releasing hormone agonist (GnRHa) (leuprolide). Mean implantation rates were 26.9 and 11.9% in the FSH-HP only and FSH-HP + rhLH groups respectively. The mean clinical pregnancy/initiated cycle rate was 64.7 and 35.7% for the FSH-HP only and FSH-HP + rhLH patients respectively. FSH-HP patients and FSH-HP + rhLH patients achieved clinical pregnancy/transfer rates of 68.8 and 45.5% respectively. One patient in the FSH-HP + rhLH group had a spontaneous abortion; no pregnancy losses occurred in the FSH-HP only group. There were more cancellations for poor ovarian response among FSH-HP + rhLH patients (n = 3) than among FSH-HP patients (n = 1). The trend toward better pregnancy outcomes among patients who received FSH-HP without supplemental rhLH did not reach statistical significance. It is postulated that appropriate endogenous LH concentrations exist despite luteal GnRHa pituitary suppression, thereby obviating the need for supplemental LH administration.

Adult↗
PubMed1997

Follicular fluid vascular endothelial growth factor concentrations are elevated in women of advanced reproductive age undergoing ovulation induction.

OBJECTIVE(S): To determine whether follicular fluid (FF) from women of advanced reproductive age had a relative deficiency of the angiogenic cytokine vascular endothelial growth factor/vascular permeability factor. Furthermore, we sought to determine whether luteinized granulosa cells secrete vascular endothelial growth factor/vascular permeability factor in response to hypoxia. DESIGN: Retrospective cohort study. SETTING: University teaching hospital. PATIENTS: Women undergoing follicular aspiration after superovulation in preparation for IVF-ET. Women of advanced reproductive age consisted of 21 women > or = 38 years old (range, 38 to 46 years); 15 subjects < or = 30 years served as the control population. INTERVENTION(S): Granulosa cells and FF were collected by transvaginal aspiration 35 hours after hCG. Granulosa cells from two women were cultured for 24 and 48 hours in M199 + 10% fetal bovine serum in 1% O2-5% CO2-94% N2 (hypoxic) or 95% air-5% CO2 (normoxic) without or with 0.1 mol/L cobalt chloride. MAIN OUTCOME MEASURE(S): Pooled FF vascular endothelial growth factor/vascular permeability factor concentrations and media vascular endothelial growth factor/vascular permeability factor accumulation at 24 and 48 hours were determined. RESULT(S): Follicular fluid vascular endothelial growth factor/vascular permeability factor concentrations were higher in advanced reproductive age women compared with younger women (3,735 +/- 2,155 versus 2,205 +/- 952 pg/mL, mean +/- SD). Accumulation of vascular endothelial growth factor/vascular permeability factor at 24 and 48 hours was 391 +/- 54 and 744 +/- 2 pg/mL in media maintained in 5% CO2 and air. Cobalt chloride induced a marked increase in vascular endothelial growth factor/vascular permeability factor (2,008 +/- 52 pg/mL at 24 hours and 3,630 +/- 519 pg/mL at 48 hours). An intermediate but significant increase in vascular endothelial growth factor/vascular permeability factor (733 +/- 35 pg/mL at 24 hours and 2,675 +/- 864 pg/mL at 48 hours) was observed with 1% O2 compared with normoxic controls. CONCLUSION(S): After hMG and hCG administration the FF from women of advanced reproductive age showed increased vascular endothelial growth factor/vascular permeability factor concentrations compared with younger women. Increased vascular endothelial growth factor/vascular permeability factor concentrations could be consistent with a hypoxic environment within follicles of older women.

Adult↗
PubMed2001

Regression of ovarian enlargement in pharmacological ovulation induction.

The aim of the present study was to determine a possible relationship between ovarian functionality and regression of ovarian enlargement according to the different categories and degree of severity of ovarian hyperstimulation syndrome (OHSS). Among a group of sterile woman (n = 111), two subgroups were studied: group A (n = 15), patients affected by severe syndrome; and group B (n = 96), patients with massive ovarian enlargement only. The protocol of ovarian stimulation was conducted in various in vitro fertilization (IVF) centers; ultrasonographic examination and hematological checks were carried out daily; patients with severe OHSS were hospitalized. In women of group A, severe symptoms disappeared in 7-11 days; in nine patients with regular cycles ovary size returned to normal in about 30-40 days, whereas in six subjects with anovulatory cycles, the resolution was recorded in about 50-60 days; serum estradiol returned to physiological levels within 20-30 days. Women of group B showed a spontaneous regression at different times: in 43 subjects that presented regular ovulatory cycles, the resolution was recorded in about 30-40 days, whereas in 36 women with anovulatory cycles before pharmacological induction, resolution occurred in 50-60 days, and in 17 cases with polycystic ovary syndrome before pharmacological ovulation, an incomplete resolution was obtained; serum estradiol levels returned to a physiological range within 20-30 days. Our results show that in patients with regular ovulatory cycles, resolution of symptoms is obtained in a shorter time than in patients with anovulatory cycles before pharmacological induction.

Adult↗
PubMed2005

Recombinant versus urinary human chorionic gonadotrophin for ovulation induction in assisted conception.

BACKGROUND: For the last few decades urinary human chorionic gonadotrophin has been used to induce final follicular maturation and for triggering ovulation in assisted conception. Recombinant technology has allowed the production of two drugs that can be used for the same purpose: to mimic the endogenous luteinizing hormone (LH) surge. This would allow commercial production to be adjusted according to market requirements. In addition all urinary contaminants would also be removed. Hence, this would allow the safe subcutaneous administration of a compound with less batch-to-batch variation. However, prior to a change in practice, the effectiveness of the recombinant drugs should be known, compared to the currently used urinary human chorionic gonadotrophins. OBJECTIVES: To assess the safety and efficacy of subcutaneous rhCG and high dose rLH compared with intramuscular uhCG for inducing final oocyte maturation and triggering ovulation. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (27 August 2003), the Cochrane Central Register of Controlled Trials (CENTRAL on The Cochrane Library, issue 4, 2003), MEDLINE (1966 to Feb 2004) and EMBASE (1980 to Feb 2004). Searches were not limited by language. The bibliographies of included, excluded trials and abstracts of major meetings were searched for additional trials. Authors and pharmaceutical companies were contacted for missing and unpublished data. SELECTION CRITERIA: Two reviewers independently scanned titles and abstracts, and selected those that appeared relevant for collection of the full paper. Only truly randomised controlled trials comparing rhCG or high dose r-LH with urinary hCG for triggering ovulation in assisted conception for treatment of infertility in normogonadotrophic women were included. DATA COLLECTION AND ANALYSIS: Assessment of inclusion/exclusion, quality assessment and data extraction were performed independently by at least two reviewers. Discrepancies were discussed in the presence of a third reviewer and a consensus reached. Quality assessment included method of randomisation, allocation concealment, blinding of participants and assessors, reporting of a power calculation, intention to treat analysis, and handling of dropouts. Data extraction included characteristics of participants, the intervention and control procedures, and outcomes. MAIN RESULTS: Seven RCTs were identified, four comparing rhCG and uhCG and three comparing rhLH and uhCG. There was no statistically significant difference between rhCG vs uhCG regarding the ongoing pregnancy/ live birth rate (OR 0.98, 95% CI 0.69 to 1.39), pregnancy rate, miscarriage or incidence of OHSS. There was no statistically significant difference between rhLH vs uhCG regarding the ongoing pregnancy/ live birth rate (OR 0.94, 95% CI 0.50 to 1.76), pregnancy rate, miscarriage or incidence of OHSS. The manufacturer of rhLH has decided not to further develop this product. rhCG was associated with a reduction in the incidence of local site reactions and other minor adverse effects (OR 0.47, 95% CI 0.32 to 0.70). AUTHORS' CONCLUSIONS: There is no evidence of difference in clinical outcomes between urinary and recombinant gonadotrophins for induction of final follicular maturation. Additional factors should be considered when choosing gonadotrophin type, including safety, cost and drug availability.

Chorionic Gonadotropin↗
PubMed1994

[Functional state of the reproductive system in patients with the hypogonadotropic form of amenorrhea during use of various protocols of ovulation induction with human menopausal gonadotropins].

Clinico-hormonal parameters of cycles stimulated with human menopausal gonadotropins in patients with hypogonadotropic amenorrhea and of spontaneous cycles in healthy women of reproductive age are compared. Estradiol hypersecretion in both phases of induced cycle was revealed: hydrocortisone in phase 1 and progesterone and testosterone in phase 2. Dexamethasone in daily dose 0.25 mg was administered for correction. This resulted in a noticeable reduction of estradiol hyperproduction in the first phase of stimulated cycles and in hyperandrogenism elimination. Folliculogenesis, ovulation, and early embryogenesis conditions in schemes of induction with human menopausal gonadotropins and dexamethasone therapy were close to physiologic ones, this resulting in increased share of fertile cycles.

Adult↗
PubMed1989

The effect of gonadotropin suppression on the induction of ovulation in premature ovarian failure patients.

Ovulation induction in patients with hypergonadotropic premature ovarian failure is rarely successful. The authors have attempted to reproduce the results of recent case reports that suggest that ovulation and pregnancy can be successfully achieved when estrogen therapy precedes or coincides with ovarian stimulation with human menopausal gonadotropins (hMG). Fourteen patients with idiopathic premature ovarian failure underwent gonadotropin suppression and attempted ovulation induction with at least one of three regimens, which were as follows: 1) Group A: estrogen-induced suppression followed by hMG stimulation (n = 4). 2) Group B: estrogen-induced suppression followed by hMG stimulation with concomitant estrogen therapy (n = 10). 3) Group C: gonadotropin-releasing hormone agonist-induced gonadotropin suppression followed by concomitant hMG stimulation (n = 6). Despite complete gonadotropin suppression and high-dose hMG therapy in all three groups, ovulation occurred in only a single patient in group C. Pregnancy did not ensue. These data fail to corroborate previous case reports.

Adult↗
PubMed1995

Pharmacological interventions for the induction of ovulation.

Ovulation induction is the most common medical intervention for the treatment of infertility. Clomifene is generally the first treatment choice for patients with amenorrhoea, unless there is profound hypothalamic deficiency. When clomifene fails to induce ovulation, menotropins (human menopausal gonadotrophin) or gonadotrophin-releasing hormone (GnRH) are effective, most notably in WHO group 1. In this condition associated with low estrogen and gonadotrophin levels, the aggregate of reported pregnancy rates is 25% per cycle. In hyperprolactinaemic anovulation bromocriptine reduces prolactin levels and thereby restores normal cyclicity. In all of the above conditions, the pharmacological agent addresses a specific defect in an explicit manner. WHO group 2 ovulatory disorders arise from hyperandrogenicity and other conditions that respond less predictably to gonadotrophin therapy. In women with WHO group 2 disorders, the aggregate of reported pregnancy rates is 8%. Ovulation induction is also used in ovulatory infertile women to generate multiple follicles and increase the likelihood of fertilisation. The aggregate of pregnancy rates in clomifene trials was 7% per cycle, and 6% in gonadotrophin trials. Gonadotrophin therapy is more effective, however, in association with assisted reproduction techniques. The contrasting treatment success in discrete disorders (25% per cycle) and heterogeneous disorders such as WHO group 2 and persistent infertility (6 to 8% per cycle) underlines the need for research to discover specific causal mechanisms and identify explicit new pharmacological interventions.

Bromocriptine↗
PubMed1985

Induction of ovulation in phase I of the in vitro fertilization and embryo transfer programme at Tygerberg Hospital.

Two different protocols for ovulation induction used in phase I of the in vitro fertilization (IVF) programme at Tygerberg Hospital are presented. Previous experience with gonadotrophins and clomiphene citrate was applied in the development of the protocols. By means of experience gained during ovulation induction it was possible to establish critical values for the parameters of follicle maturity, which are used to determine the optimal time for follicle aspiration. Ultrasonically measured follicle size, critical serum oestradiol levels for each mature follicle and cervical mucus scoring were the parameters used. Fifty-one ova were obtained during 29 of the 34 attempts at follicle aspiration. Only 5 of the ova were immature. At least 1 mature ovum was obtained at 80% of all laparoscopies. Twenty-three embryos were transferred to 15 patients, and 3 pregnancies occurred. As a result of this programme 2 babies were born--the first in South Africa by IVF and embryo transfer.

Clomiphene↗
PubMed1991

Early miscarriage and fetal malformations after induction of ovulation (by clomiphene citrate and/or human menotropins), in vitro fertilization, and gamete intrafallopian transfer.

From the reviewed data, it appears that CC, hMG-hCG, or the association of these drugs with IVF-ET and GIFT programs do not carry an increased risk for congenital malformations as a whole, nor is there any specific malformation that has an increased incidence or is related in any way with the use of these drugs. Table 7 represents the specific malformation rate per 1,000 births in the general population and in newborns delivered after treatment with CC, hMG-hCG, or IVF-ET and GIFT. The malformation rate in the treated groups does not differ from that of the general population. However, as shown by McIntosh et al., the incidence of congenital malformations often rises with a longer follow-up. Most of the reports about babies born after ovulation induction are based on the initial examination done shortly after birth. Thus, studies including examination of these infants up to at least 12 months of age will be undoubtedly of value. Also, data concerning the reproductive capability of women born after ovulation induction is lacking. With regard to the abortion rate in pregnancies achieved after such treatments and procedures, it can be concluded that it does not appear to be higher than that of the general population, particularly when early pregnancy loss, advanced maternal age, the infertility status, and the increased incidence of multiple pregnancies occurring in these patients are taken into consideration.

Abortion, Spontaneous↗