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PubMed2003

Maternal adjustment, parenting and child behaviour in families of school-aged twins conceived after IVF and ovulation induction.

BACKGROUND: Previous studies that have examined the long-term effects of infertility and assisted reproductive technology on parenting and child behaviour in families with twins have suffered from methodological problems. This study compared measures of parental adjustment, parenting and child behaviour in families with 5-year-old twins who were conceived after in vitro fertilisation (IVF) or ovulation induction (OI) with families whose twins were naturally conceived (NC). METHODS: The families who conceived via IVF/OI (N = 121) were identified from an epidemiological study of twins and matched to families who were conceived naturally (N = 121) on the basis of eleven child and family variables. Mothers were interviewed in their homes for the study. RESULTS: No significant differences were observed between the IVF/OI families and the NC families on measures of parental adjustment or parent and teacher ratings of the twins' behaviour. IVF/OI mothers and their partners agreed with each other about discipline more than NC couples, but otherwise no other differences in parenting were found. CONCLUSIONS: Overall, this study provides evidence that families who conceive twins following IVF/OI are functioning well and that the experience of fertility treatment does not lead to long-term difficulties for parents or children.

Adaptation, Psychological↗
PubMed2001

Ovulation induction with pulsatile gonadotropin-releasing hormone (GnRH) or gonadotropins in a case of hypothalamic amenorrhea and diabetes insipidus.

Hypothalamic amenorrhea is a treatable cause of infertility. Our patient was presented with secondary amenorrhea and diabetes insipidus. Cortisol and prolactin responded normally to a combined insulin tolerance test (ITT) and thyrotropin-releasing hormone (TRH) challenge, while thyroid-stimulating hormone (TSH) response to TRH was diminished, and no response of growth hormone to ITT was detected. Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels increased following gonadotropin-releasing hormone (GnRH) challenge. No response of LH to clomiphene citrate challenge was detected. Magnetic resonance imaging findings demonstrated a midline mass occupying the inferior hypothalamus, with posterior lobe not visible and thickened pituitary stalk. Ovulation induction was carried out first with combined human menopausal gonadotropins (hMG/LH/FSH) (150 IU/day) and afterwards with pulsatile GnRH (150 ng/kg/pulse). Ovulation was achieved with both pulsatile GnRH and combine gonadotropin therapy. Slightly better results were achieved with the pulsatile GnRH treatment.

Adult↗
PubMed1984

Monitoring techniques for improved pregnancy rates during clomiphene ovulation induction.

Despite the introduction of new ovulation-inducing agents, CC remains the drug of choice for most anovulatory patients. Before initiating therapy, patients should be evaluated to determine the cause of anovulation. Patients with ovarian failure, hyperprolactinemia, hypothyroidism, or forms of CAH should be treated with the appropriate replacement therapy. Evaluation of male factor and tubal patency should be obtained. Once CC therapy is initiated, careful monitoring should be continued. Confirmation of ovulation by endometrial biopsy or serum P levels is essential. CC doses should be increased monthly until normal luteal function is demonstrated. If the patient does not conceive in three ovulatory cycles, her treatment should be further evaluated by postcoital testing, repeat serum P measurement, and review of her endocrine findings. Patients with poor cervical mucus may benefit from midcycle estrogen. Patients with elevated T may benefit from prednisone suppressive therapy. Patients with abnormal HSGs should have laparoscopy and surgical correction if feasible. After six ovulatory cycles without conception, all patients should undergo laparoscopy. If laparoscopy is normal, therapy can be continued for a total of 10 to 12 cycles. Patients with reduced fecundability (male factor, minimal endometriosis, or minimal tubal adhesions) may require a longer time to conceive.

Adrenal Hyperplasia, Congenital↗
PubMed1986

Ovulation induction with low doses of clomiphene citrate.

Ovulation was induced with one-quarter tablet (12.5 mg) of clomiphene citrate given for five days to three oligoovulatory patients who had consistently formed functional ovarian cysts when given 50 and 25 mg of clomiphene citrate for five days. Two of the patients had polycystic ovary syndrome and the other had hypothalamic dysfunction associated with an eating disorder. On clomiphene citrate 12.5 mg for five days, one patient conceived, another produced inadequate cervical mucus but later conceived after in vitro fertilization and embryo transfer, and the third woman, who had concomitant fallopian tube disease, ovulated but has not conceived. Women oversensitive to clomiphene citrate can be effectively treated with very low doses of the drug. Perhaps other oligoovulatory patients may benefit from lower than currently recommended clomiphene citrate doses.

Adult↗
PubMed1995

[Use of a gonadoliberin agonist with or without gonadoliberin pulses for ovulation induction in ovarian dystrophies].

OBJECTIVES: Determine whether ovulation in dystrophic ovaries treated with GnRH agonist followed by GnRH pulses is due to the GnRH pulse or is patient-dependent. SITE. Endocrinology department, CHU Purpan, Toulouse, France. METHODS: Fifteen infertile patients, age range 22 to 35 years, with ovarian dystrophy were given GnRH agonist (Decapeptyl, 3.75 mg IM on day 3 of the cycle). In 5 patients, an IV pulse of GnRH was then given (6 micrograms/90 min). STATISTICAL ANALYSIS: Mann-Whitney U test, corrected chi 2 test. RESULTS: Ovulation was achieved in 8/15 cases (3/5 with and 5/10 without pulsatile GnRH p = NS) and 3 pregnancies (without pulsatile GnRH). Before treatment LH was higher in patients who had an ovulation. CONCLUSION: Ovulation can be achieved after GnRH agonist treatment in patients with dystrophic ovaries, with or without pulsatile GnRH, particularly if the initial LH levels are high.

Adult↗
PubMed1996

Dexamethasone as an adjuvant therapy for anovulatory, normoandrogenic patients during ovulation induction with exogenous gonadotropins.

OBJECTIVE: The objective of our study was to explore the effect of dexamethasone (DEX), a highly potent, long-acting glucocorticoid, on the treatment outcome of 74 anovulatory women aged 21 to 29 years, with normal gonadotropins, androgen, and prolactin (PRL) serum levels who failed to conceive on antiestrogen therapy. METHODS: The patients received human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG) for ovulation induction. Starting on day 4 of the induced menstruation, hMG was administered in combination with DEX, 0.5 mg at night, or without DEX as an adjuvant treatment. The total amount of gonadotropins used, time required for stimulation, percentage of fertilization, serum estradiol levels, pregnancy rate, cumulative pregnancy rate, and abortions were recorded. RESULTS: There were no differences in either the cumulative pregnancy rate (54.1% in the DEX group and 52.7% in the untreated group) or the abortion rates (21.7% in the DEX group compared to 20.8% in the untreated group). The other parameters investigated also did not differ significantly between the groups. CONCLUSIONS: The overall results did not support DEX as a clinically useful adjuvant therapy for anovulatory, normoandrogenic patients.

Abortion, Spontaneous↗
PubMed2000

Pulsatile luteinising hormone releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome.

BACKGROUND: In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intra-venous or subcutaneous route using a portable pump has been used successfully in patients with hypogonadotrophic hypogonadism. Assuming that the results would be similar in polycystic ovary syndrome (PCOS), pulsatile GnRH has been used to induce ovulation in patients with PCOS. But, although ovulation and pregnancy has been achieved, the use of pulsatile GnRH in PCOS patients is controversial. OBJECTIVES: To assess the effectiveness of pulsatile GnRH administration in women with clomiphene-resistant polycystic ovary syndrome (PCOS), in terms of ovulation induction, pregnancy, miscarriage, multiple pregnancy and ovarian hyperstimulation syndrome (OHSS). SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility review group was used to identify all relevant trials. Please see Review Group details. SELECTION CRITERIA: All relevant published RCTs were selected. Non-randomised controlled trials were eligible for inclusion if treatment consisted of GnRH administration versus another treatment to induce ovulation in subfertile women with PCOS. DATA COLLECTION AND ANALYSIS: A computerised MEDLINE and EMBASE search was used to identify randomised and non randomised controlled trials. The reference lists of all studies found were checked for relevant articles. One RCT (Bringer 1985a) and one abstract (Coelingh 1983) were identified this way. Relevant data were extracted independently by two reviewers (NB, MW). Validity was assessed in terms of method of randomization, completeness of follow-up, presence or absence of cross-over and co-intervention. All trials were screened and analysed for predetermined quality criteria. DATA SYNTHESIS: 2X2 tables were generated for all the relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. MAIN RESULTS: Three RCTs and one non-randomised comparative trial were identified comparing four different treatments: GnRH versus HMG, GnRH following GnRHa pre-treatment versus no pre-treatment, GnRH and FSH versus FSH, and GnRH following GnRHa pre-treatment versus GnRH following oral contraceptive pre-treatment. This means that there was only one trial in any one comparison. In the first two studies, data of pre- and post-cross-over were not described separately. Therefore, these results could not be included in the MetaView analysis. The odds ratio for ovulation rate was 16 (95 % CI: 1.1-239) in the study comparing GnRH and FSH with FSH. When GnRH after GnRHa pre-treatment was compared with GnRH after oral contraceptive pre-treatment, an odds ratio of 7.5 (95 % CI: 1.2-46) was obtained. All trials were small and of too short duration to show any significance in pregnancy results. Per study only one to four pregnancies occurred. Multiple pregnancies were not seen. OHSS was seen only in the patients stimulated with HMG. REVIEWER'S CONCLUSIONS: The four trials describing four different comparisons with a short follow up (1 to 3 cycles) were too small to either prove or discard the value of pulsatile GnRH treatment in patients with polycystic ovary syndrome.

Female↗
PubMed1991

Combined growth hormone and gonadotropin treatment for ovulation induction in patients with non-responsive ovaries.

Four anovulatory patients who did not respond to large doses of hMG over 18-33 days were co-treated in subsequent cycles with human growth hormone. Treatment with growth hormone markedly raised serum insulin-like growth factor concentrations. Two patients had a dramatic ovarian response within 7 days of co-treatment; two menopausal patients did not respond. This combined therapy may be of practical value for ovulation induction in non-menopausal patients with non-responsive ovaries.

Addison Disease↗
PubMed2003

Human granulosa cells after ovulation induction show caspase-independent cell death.

It has become clear that apoptosis is an essential part of normal folliculogenesis and that granulosa cells in particular demonstrate intense cellular activity as well as programmed cell death. Although the entire mechanism of apoptosis appears to be conserved through many species, it now becomes clear that different cells may use different pathways within this system. We examined human granulosa cells after ovulation induction during an in vitro fertilization procedure to study apoptosis in this particular situation. We demonstrated a loss of cytokeratin staining as granulosa cells differentiate. We also detected that granulosa cells with apoptotic morphology did not stain for terminal deoxy-UTP nick end labeling and we showed the absence of immunoreactivity for caspase-cleaved cytokeratin, caspase-cleaved poly-ADP-ribose polymerase and caspase-cleaved caspase-3 in apoptotic granulosa cells. These data provide strong arguments for a caspase-independent cell death mechanism in human granulosa-lutein cells.

Apoptosis↗
PubMed2006

A prospective randomized trial comparing anastrozole and clomiphene citrate in an ovulation induction protocol using gonadotropins.

OBJECTIVE: To compare the ovarian and endometrial effects of anastrozole and clomiphene when used with gonadotropins in a combination protocol. DESIGN: Prospective randomized trial. SETTING: Academic infertility center. PATIENT(S): Fifty infertile women. INTERVENTIONS(S): Women were randomized to receive either 1 mg anastrozole or 100 mg clomiphene citrate for 5 days (cycle days 3-7) followed by FSH injections (days 7-11) for ovulation induction. A subset participated in a crossover arm of the study. MAIN OUTCOME MEASURE(S): Ovarian follicle number and size, E(2) levels, endometrial thickness, pregnancy, and cancellation rates. RESULT(S): On cycle day 12, anastrozole cycles were associated with fewer total follicles (1.4 vs. 3.6, P=0.01), fewer mature follicles (0.6 vs. 1.6, P<.01), lower serum E(2) (131 pg/mL vs. 613 pg/mL, P<.01,) and the same endometrial stripe thickness compared with clomiphene citrate cycles. Cycle cancellation rates were similar between the two groups. On the day of hCG administration in noncancelled cycles, anastrozole cycles were associated with fewer total follicles (1.6 vs. 3.8, P<.01), fewer mature follicles (1.3 vs. 2.1, P<.01), and an equal endometrial stripe thickness compared with clomiphene citrate cycles. Pregnancy rates were similar between clomiphene (20%) and anastrozole (12%) cycles. CONCLUSION(S): Anastrozole when used in conjunction with gonadotropins results in lower E(2) levels and fewer follicles than clomiphene citrate. A combination protocol of anastrozole and gonadotropins may be a safer protocol for patients at higher risk of hyperstimulation and multiple births after infertility treatments.

Administration, Oral↗
PubMed1995

Exploring the recovery phase after treatment with a gonadotrophin-releasing hormone-agonist for ovulation induction in polycystic ovary syndrome: three pilot trials.

OBJECTIVE: Guided by the favorable results of pulsatile gonadotrophin-releasing hormone (GnRH) in the recovery phase after GnRH agonist (GnRH-a) in PCOS, two hypotheses concerning the recovery phase were tested: (1) The resistance to clomiphene citrate will be broken in the recovery phase. (2) Stimulation with (i) a fixed dose of follicle stimulating hormone (FSH) or (ii) with the GnRH-a itself is equally effective in inducing ovulation as pulsatile GnRH. DESIGN: After discontinuation of a 17-21 days GnRH-a treatment, ovulation induction was attempted with clomiphene citrate (CC) or with a fixed dose of FSH or with GnRH-a itself in three separate pilot trials. A previously reported group of 12 patients, treated with pulsatile GnRH in the recovery phase served as control. PATIENTS: Three groups of six patients having PCOS. The group treated with CC was a selected CC-resistant group. RESULTS: No CC-treated patient ovulated. After FSH stimulation two patients ovulated, and one patient ovulated on stimulation with a low dose of the GnRH-a. Endocrine observations in the recovery phase showed an early rise of FSH as compared to the rise of LH and androgens. CONCLUSION: This study could not demonstrate any effect of the recovery phase with respect to facilitation of follicular growth in PCOS. Both tested hypotheses were rejected: (1) The resistance to CC appeared not to be broken by the GnRH-a treatment and (2) subsequent stimulation with FSH or with the GnRH-a itself were not as effective as stimulation with pulsatile GnRH. An extensive further study of the mentioned modalities did not seem feasible.

Adult↗
PubMed2002

Metformin does not enhance ovulation induction in clomiphene resistant polycystic ovary syndrome in clinical practice.

AIMS: To determine whether metformin pretreatment has beneficial effects in clomiphene resistant infertile women with polycystic ovary syndrome (PCOS) in an infertility clinic. METHODS: This was a randomized placebo controlled double-blind crossover study of 3 months metformin (1500 mg day-1)/placebo, followed by 3 months metformin/placebo together with clomiphene (50-100 mg for 5 days) for three cycles in clomiphene resistant women with PCOS. The primary outcomes were restoration of spontaneous menses, ovulation induction (spontaneous or clomiphene induced) and pregnancy. Secondary endpoints were changes in biochemical parameters related to androgens and insulin. RESULTS: Twelve women completed the metformin arm and 14 the placebo arm. Spontaneous menstruation resumed in five metformin treated patients and in six placebo treated women, P=0.63. No women given metformin spontaneously ovulated, although one patient given placebo did, P=0.30. There was no difference in the efficacy of clomiphene between the two groups with ovulation being induced in five (out of 12) metformin treated women and four (out of 14) placebo treated women, P=0.63. Pregnancy occurred in three (out of 12) women given metformin and two (out of 14) women given placebo, P=0.59. CONCLUSIONS: Metformin is not always beneficial when given to clomiphene resistant infertile women with PCOS in clinical practice.

Adult↗
PubMed1993

The duration of leuprolide acetate administration prior to ovulation induction does not impact ovarian responsiveness to exogenous gonadotropins.

OBJECTIVE: To evaluate the possible impact that the duration of GnRH agonist (GnRH-a) suppression has on subsequent ovarian responsiveness to exogenous gonadotropins. DESIGN: Prospective evaluation of the relationship between the duration of GnRH-a and multiple parameters of ovarian responsiveness. SETTING: Assisted reproduction program in a large military tertiary care center. PATIENTS: One hundred sixty-five women being pretreated with leuprolide acetate (LA) before ovulation induction with exogenous gonadotropins. INTERVENTIONS: Variable duration of LA administration before stimulation. MAIN OUTCOME MEASURES: Outcome measures include duration of stimulation, days until doubling of basal E2, number of ampules of exogenous gonadotropins, peak E2, number of mature follicles, and number of mature oocytes. RESULTS: The duration of LA pretreatment had no effect on any of the parameters of ovarian responsiveness analyzed. CONCLUSION: Once complete suppression of gonadal function is attained, the duration of GnRH-a suppression has no impact on subsequent ovarian responsiveness to exogenous gonadotropins.

Adult↗
PubMed1998

Can we advise ovulation induction in patients with SLE?

The prognosis of systemic lupus erythematosus (SLE) has greatly improved during the last two decades, now allowing most patients to have a very long survival including a satisfactory quality of life. Initially considered contraindicated in SLE due to its overwhelming risks, pregnancy is nowadays allowed in a majority of patients, and fair results are usually obtained under appropriate management (1-3). Consequently, patients thought to have infertility ask the question of a possible therapy, i.e. ovulation induction (OI) associated or not with in vitro fertilization (IVF). Considering the importance of estrogens in the pathogenesis of the disease, the use of such procedures raise several questions in SLE. Though data remain to date extremely scarce, the theoretical and practical aspects of OI in SLE will be briefly reviewed here.

Adult↗
PubMed1987

[Ovulation induction with pulsatile gonadotropin-releasing hormone and continuous human menopausal gonadotropin in polycystic ovarian disease].

Various treatments have been applied to polycystic ovarian (PCO) type of anovulation. However, none of them was definitive in terms of the efficacy and side effects. Six anovulatory women of PCO type were treated with pulsatile gonadotropin-releasing hormone (GnRH) of various pulse intervals and continuous human menopausal gonadotropin (hMG). The efficacy and rationale of the treatments were discussed. The subjects were diagnosed PCO by GnRH test and/or laparoscopy. They did not ovulate with clomiphene, clomiphene-hCG and hMG-hCG therapies. Their pretreatment serum FSH and LH levels and FSH/LH ratios were 6.9 +/- 1.2 mIU/ml, 15.7 +/- 5.1 mIU/ml, and 0.54 +/- 0.19 (Mean +/- SD), respectively. The treatment consisted of 3 protocols: 1) pulsatile GnRH (5-10 micrograms/pulse) of 90 min interval, 2) pulsatile GnRH (5-10 micrograms/pulse) of 120 min interval and 3) continuous hMG (150 IU/day) through subcutaneous route. Follicular growth was monitored sonographically and an intramuscular bolus of 10,000 IU hCG was given when the dominant follicle reached 20 mm in diameter. During both GnRH treatments serum FSH levels and FSH/LH ratios did not elevate substantially. Serum LH, E2 and PRL levels elevated acutely and transiently during the initial phase of GnRH treatments. Follicular growth was observed in a small fraction of the cases, but none of them ovulated. In contrast, continuous hMG treatment induced significant elevation in serum FSH levels (8.2 +/- 1.7 mIU/ml; p less than 0.01) and FSH/LH ratios (1.73 +/- 0.57; p less than 0.001). Transient hyperprolactinemia was accompanied with the preovulatory E2 rise. All the cases ovulated and 3 singleton pregnancies followed. These findings draw conclusions as follows. Pulsatile GnRH administration may desensitize the pituitary presumably due to increased GnRH pulse frequency as a consequence of two independent pulse generators, intrinsic and exogeneous. It may induce transient hyperprolactinemia through a paracrine system between gonadotrophs and lactotrophs. As a due course pulsatile GnRH therapy is questionable for ovulation induction in cases with functioning hypothalamic-pituitary axis. The fact that continuous hMG effectively induced follicle maturation with elevated FSH/LH ratios suggested that FSH dominance might be a prerequisite for folliculogenesis. The fluctuating nature of gonadotropins might not be mandatory for folliculogenesis.

Adult↗
PubMed2002

Leptin and ovarian folliculogenesis: implications for ovulation induction and ART outcomes.

Leptin participates in regulation of ovarian folliculogenesis indirectly via control of luteinizing hormone and follicle-stimulating hormone secretion. More recent evidence suggests that leptin also has direct regulatory actions on the developing follicle. The presence of leptin receptors on follicular cells, including oocytes, and early preimplantation embryos suggests that leptin may play a direct physiologic role in follicular maturation, oocyte development, and early cleavage. Because circulating leptin levels are directly related to body adiposity, elevated leptin concentrations associated with obesity may partly explain the negative impact of obesity on fertility. The influence of leptin on follicular development and oocyte maturation has important implications for ovulation induction and assisted reproductive technologies. Moreover, polycystic ovarian syndrome may be associated with altered leptin phsyiology.

Female↗
PubMed1993

Measurement of serum levels of exogenously administered FSH and LH during ovulation induction therapy.

We conducted a prospective study of blood levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) following daily intramuscular injection of human menopausal gonadotropin (hMG) containing equal proportions of FSH and LH. Blood samples were collected on alternate days and the resulting changes in the blood levels of the ovarian hormone estradiol were also monitored. Twenty-eight consecutive patients with polycystic ovary syndrome who were between the ages of 25 and 35 years and attending our infertility clinic for ovulation induction therapy and assisted pregnancy were studied. Polycystic ovary syndrome was diagnosed on laparoscopy and as evidenced by high serum LH which was three times greater than FSH in the follicular phase of the menstrual cycle. A male factor for infertility was excluded. Twenty-five out of 28 women (89.3%) receiving hMG responded to therapy by a rise in serum estradiol level (> 1200 pmol/l on day 9). Of the 25 women who responded to hMG, four had live single babies (16%). All four women showed a cumulative rise in mean serum FSH with treatment when measured by standard radioimmunoassay, reaching statistical significance on day 5 (p < 0.05). The remaining 21 who failed to become pregnant showed variable changes in mean serum FSH with a sharp rise on day 3 (p < 0.02) and a significant fall on day 7 (p < 0.02). However, mean serum LH measured by standard radioimmunoassay in all women remained unchanged throughout the period of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1996

[Ovulation induction in women in the in vitro fertilization program].

In-vitro fertilization presents a method of assisted reproduction where fusion of two gametes (fertilization) occurs in laboratory conditions. In this way part of the process which normally happens in the fallopian tube is being imitated. By ovulation the number of follicles increases, thus increasing the number of oocytes, that is the number of embryos and at the same time increasing chance of pregnancy. Ovulation induction was achieved by: clomiphene citrate (CC), human menopausal gonadotropin (hMG), human chorionic gonadotropin (hCG) and luteinizing hormone-releasing hormone (LHRH). Our trial compared effects of three induction schemes: HMG-hCG; CC-hMG-hCG and LHRH-hMG-hCG. We compared the following parameters: total number of follicles, number of mature follicles (16mm with simultaneous estradiol level 350pg/ml per follicle), number of aspirated oocytes as well as the number of embryos produced by insemination of aspirated oocytes. Our examination revealed that there was no significant difference in number of follicles, aspirated and produced oocytes in patients undergoing stimulated ovulation scheme CC-hMG-hCG in regard to those with hMG-hCG schemes. In patients undergoing LHRH-hMG-hCG scheme the number of follicles was decreased and there were less oocytes, but the number of developed embryos after oocytes insemination was increased. This leads to the conclusion that in-vitro fertilization depends on quality, not only the number of oocytes obtained by LHRH agonists induction.

Adult↗