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PubMed1992

The routine use of gonadotropin-releasing hormone agonists prior to in vitro fertilization and gamete intrafallopian transfer: a meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the efficacy of gonadotropin-releasing hormone agonists (GnRH-a) used in ovulation induction for in vitro fertilization and embryo transfer (IVF-ET) and gamete intrafallopian transfer (GIFT). DESIGN: Meta-analysis of 10 trials comparing treatment cycle outcomes after GnRH-a (n = 914) with other ovulation induction protocols (n = 722) and 7 trials comparing outcomes after short flare-up (n = 368) with longer suppression (n = 476) GnRH-a protocols. MAIN OUTCOME MEASURES: The outcome of primary interest was clinical pregnancy rate (PR) per treatment cycle commenced. Data describing the amount of gonadotropin used, cycle cancellation rate, clinical pregnancy per ET, and multiple pregnancy and abortion rates were also analyzed. RESULTS: Clinical PR per cycle commenced was significantly improved after GnRH-a use for IVF (common odds ratio [OR] 1.80, 95% confidence interval [CI] 1.33 to 2.44) and GIFT (common OR 2.37, 95% CI 1.24 to 4.51). Clinical PR per embryo transfer was also significantly improved with GnRH-a use (common OR 1.40, 95% CI 1.01 to 1.95). Cycle cancellation was decreased (common OR 0.33, 95% CI 0.25 to 0.44), whereas spontaneous abortion rate was similar with and without GnRH-a use. Cycle cancellation and PRs after short flare-up and longer suppression protocols were similar between groups. CONCLUSIONS: This meta-analysis supports the routine use of GnRH-a for IVF and GIFT. Further research is needed, however, to assess the potential for increased rates of multiple pregnancy and ovarian hyperstimulation syndrome, which may be associated with this treatment.

Abortion, Spontaneous↗
PubMed1994

Effect of mifepristone on inhibition of ovulation and induction of luteolysis.

Mifepristone administration to women in the mid- or late follicular phase delays the luteinizing hormone (LH) surge and prolongs the follicular phase. Since the resumption of follicular growth commences following mifepristone cessation, the drug must be given either continuously or at repeated intervals in order to block ovulation. Using various regimens with or without exogenous progestins, ovulation was inhibited in the majority of subjects. However, this was not consistent and in several instances, LH surges and a rise in plasma progesterone were suggestive of ovulation and corpus luteum function. Therefore, mifepristone cannot be used as a contraceptive which will reliably inhibit ovulation. With low-dose mifepristone administration, alterations in endometrial morphology were characterized by a delay in maturation despite the presence of ovulation. This suggests that the endometrium displays a greater sensitivity to mifepristone than does the pituitary, a finding that may have important contraceptive implications. Late luteal-phase mifepristone administration to women who were not sexually active did not alter their menstrual rhythm, bleeding patterns or steroid and gonadotrophin concentrations. However, when used in unprotected women in the late luteal phase, mifepristone did not uniformly terminate all pregnancies. On the other hand, when used within 72 h of intercourse, mifepristone was as effective a post-coital agent as the standard high-dose oestrogen-progestin combination.

Abortion, Induced↗
PubMed1993

Supplementary growth hormone treatment of women with poor ovarian response to exogenous gonadotrophins: changes in serum and follicular fluid insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3).

The effects of supplementary growth hormone (GH) treatment upon insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3) concentrations in serum and ovarian follicular fluid were investigated in women undergoing buserelin human menopausal gonadotrophin (HMG) ovulation induction for in-vitro fertilization. Women (n = 40), aged 24-39 (mean 35 years), who showed poor ovarian responses to HMG, were recruited and randomly divided into two groups. Each patient received two cycles of ovulation induction, one with GH (12 IU/day x 12 days/HMG/buserelin) and another with placebo/HMG. Serum IGF-1 increased substantially during the GH treatment and remained significantly higher than the control 2 days after the last GH injection. Serum IGFBP-3 fell steadily during the placebo/HMG treatment and to a nadir on the day of oocyte retrieval (P < 0.05 compared to serum before any treatment). In contrast, IGFBP-3 was increased (P < 0.01) during the GH administration and returned to the control level 2 days after GH injection. Serum oestradiol concentrations on the eighth day of HMG and the day of human chorionic gonadotrophin (HCG) were not significantly different between the two groups. Serum IGF-1 was highly correlated with IGFBP-3 before any treatment (r = 0.433, P < 0.001). This correlation disappeared after buserelin, placebo/HMG treatment in the control group, but it was maintained during GH/HMG treatment (r = 0.343, P = 0.04). Follicular fluid concentrations of GH and IGF-1, not IGFBP-3 or oestradiol, were significantly elevated in the GH-treated women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2005

Fimbrio-ovarian relationship in unexplained infertility.

INTRODUCTION: The role of defective fimbrio-ovarian relation in cases of unexplained infertility has not been extensively studied. The aim of the study was to assess the role of fimbrio-ovarian relation as an investigative modality in women with unexplained infertility. We also aimed to evaluate the efficacy of superovulation and freeing the fimbria-ovarica in increasing the conception rate of women with unexplained infertility. MATERIALS AND METHODS: This was a prospective study where out of 80 infertile couples, 19 women with unexplained infertility were recruited as study group. Fifteen fertile women were recruited as control group. During laparoscopy the length of the fimbria-ovarica and the ovulation border was measured. The fimbrio-ovarian accessibility test was demonstrated by holding the tubal fimbria by a non-traumatizing grasper and their ability to reach or cover the ovulation site. The freeing of the fimbria-ovarica was done, if its length was less than 2 cm. All cases were given ovulation induction for consecutive six cycles and were followed up to document any conception. RESULTS: The mean length of the fimbria-ovarica was significantly less in patients with unexplained infertility (2.5 +/- 0.6 vs. 3.55 +/- 0.8 cm). The mean length of the ovulation border was not significantly different in cases and controls (2.95 +/- 0.6 vs. 3.55 +/- 0.5 cm). The fimbrio-ovarian accessibility test was positive in 6 (31.5%) cases and in 14 (93%) controls. The fimbrio-ovarian accessibility test was negative in 13 (68.4%) cases and in 1 (7%) control. Out of the 13 cases with negative FOAT, 7 had fimbrial length less than 2 cm and in whom the freeing of fimbria-ovarica was done because of severe resistance during stretching. Out of 7 patients in whom freeing of fimbria-ovarica was done 3 conceived (42.8%). Out of the 12 patients who got only ovulation induction 3 conceived (25%). CONCLUSION: Fimbrio-ovarian accessibility test appears to be a promising investigative modality to assess ovarian pick-up in patients with unexplained infertility. Correcting fimbrio-ovarian relation (freeing short fimbria-ovarica) improves pregnancy rate in women with unexplained infertility.

Adult↗
PubMed2004

Inhibins and adult ovarian function.

Inhibin B is predominantly produced by early healthy antral follicles during the luteo-follicular transition of the menstrual cycle. High inhibin B concentrations during the early follicular phase are responsible for the decline in FSH serum levels closing the FSH window and assuring single dominant follicle selection in the human. Early follicular phase inhibin B levels decrease over time, reflecting the recruitment of a diminished cohort of follicles with ovarian ageing. Hence, inhibin B is a predictor of poor response in IVF. In patients with PCOS inhibin B levels (potentially representing the number of healthy, early antral follicles) may be associated with the severity of ovarian dysfunction and consequently may predict ovulation induction outcome. However, inhibin B levels are normal in most PCOS patients suggesting a normal number of healthy follicles despite an increase in overall follicle number. Recent findings indicate that initial inhibin B concentrations can not predict the outcome of ovulation induction by either clomiphene citrate or FSH. Finally, inhibin B levels decrease over time in PCOS.

Adult↗
PubMed1999

Are there any relationships between the fecundity of bilateral ovaries in an individual patient and the incidence of apoptotic granulosa cells?

Many researchers have discussed fecundity on a per patient or per ovarian follicle basis. In contrast, this study was undertaken on a per ovary basis, and tests the hypothesis that there is a relationship between the fecundity of the bilateral ovaries in an individual patient and the incidence of apoptotic granulosa cells. The two ovaries of 10 women undergoing ovulation induction for in-vitro fertilization (IVF) with gonadotrophin-releasing hormone analogue (GnRHa) and gonadotrophins were compared. There was no difference in apoptotic index in granulosa cells and various hormones in the follicular fluids. Our results indicate that, in the ovulation induction protocol for IVF, GnRHa and gonadotrophins, there is no predisposition of one ovary over the other in an individual patient in terms of apoptosis at the time of aspiration, even though the number of oocytes in each ovary is different, because the number of oocytes retrieved may reveal ovarian fecundity before stimulation with GnRHa + human menopausal gonadotrophin (HMG).

Apoptosis↗
PubMed1985

Effects of interrupted photoperiods on the induction of ovulation in anestrous mares.

The ability of interrupted photoperiods to induce early estrus and ovulation was examined. Horse mares were exposed to long (16 h light) or short (10 h light), noninterrupted photoperiods, ambient light, or various interrupted photoperiod treatments from December 1 to April 15 (135 d). Follicular development was assessed by rectal palpation and estrous behavior was determined by teasing with a stallion. Serum concentrations of progesterone were used as an indicator of corpus luteum function. Differences among the light treatment groups were compared for the following behavioral and ovarian characteristics: days to first detectable 3-cm follicle, days to first estrous behavior, days to first ovulation, the number of mares ovulating within the treatment period, and the number of ovulations within the treatment period per mare. Compared with the ambient and 10L:14D (L = h of light and D = h of darkness) photoperiod treatments, ovulation was advanced to the greatest extent by a photoperiod of 16L:8D and the interrupted photoperiod 10L:8D:2L:4D. These two stimulatory photoperiod treatments were characterized by the presence of light 8 to 10 h after dusk. Therefore, the present data are consistent with an external coincidence model for the induction of seasonal breeding in horses, with the photoinducible phase occurring within the period 8 to 10 h after dusk.

Animals↗
PubMed2000

Patient selection for assisted reproductive technology treatments.

Assisted reproductive technologies refer to procedures in which the oocyte is handled or manipulated in vitro before replacement, either as an oocyte or an embryo. Because of rapid advances in this area, infertile couples may seek direct referral for assisted reproductive treatments, instead of trying simpler measures such as ovulation induction and intrauterine insemination. It is important to establish whether these conventional infertility treatments are appropriate, as such treatments are generally safer, less stressful, and more affordable. On the other hand, subjecting infertile couples to unnecessary delay by offering inappropriate treatments-for example, ovulation induction for tubal infertility or intrauterine insemination for severe male-factor infertility-would reduce the overall chance of success because of the age-related decline in female fecundity. The choice of infertility treatments thus depends on a balance of factors: the chance of pregnancy without treatment; the chance with simpler and safer, but less successful, infertility treatments; or the chance with the more complex and costly, but more effective, assisted reproductive treatments. The factors that should be taken into consideration include the age of the woman, the duration of infertility, the causes of infertility, the availability and cost of alternative treatments, and-most importantly-the acceptability.

Anovulation↗
PubMed1996

Use of endometrial measurement as an exclusion criterion for in vitro fertilization using clomiphene citrate.

OBJECTIVE: Previous reports have indicated an association between endometrial development and pregnancy outcome for patients treated with clomiphene citrate (CC) in conjunction with intrauterine insemination or intercourse. We expanded the use of CC for ovulation induction in association with in vitro fertilization (IVF). This study was designed to determine if endometrial thickness should be used as an inclusion or exclusion criterion for CC-IVF. STUDY DESIGN: One hundred twenty-eight patients were enrolled in an ovulation-induction regimen using CC for expected IVF-ET between January 1992 and December 1992. A total of 81 patients met inclusion criteria for CC-IVF and had endometrial measurement performed prior to human chorionic gonadotropin administration. Patients were categorized on the basis of endometrial measurement as follows: (A) > 4 - < 7 mm, (B) > or = 7 - < or = 10 mm, and (C) > 10 mm. Standard IVF was performed, and pregnancy rates for each category were evaluated. RESULTS: A total of 23 pregnancies (28% per retrieval) were established. Pregnancy rates were not different by category (P > .10, Fisher's Exact Test): (A) 3/15 (20%), (B) 13/41 (32%), and (C) 7/25 (28%). CONCLUSION: These data suggest that for CC-IVF. endometrial measurement should not be used as an exclusion criterion since pregnancies occurred at comparable frequencies in all the groups.

Adult↗
PubMed2003

Insulin-like growth factor (IGF)-1 and IGF binding protein-1 and -3 in the follicular fluid of infertile patients with endometriosis.

BACKGROUND: Endometriosis is associated with pituitary-ovarian axis dysfunction. The study of the follicular fluid in patients with endometriosis is important to elucidate the pathophysiological mechanism of this disease. The objective of this present paper was to analyse the dosages of insulin-like growth factor-1 (IGF-1) and IGF binding protein-1 and 3 (IGFBP-1 and IGFBP-3) in the follicular fluid environment of infertile patients with endometriosis. METHODS: A total of 41 infertile patients undergoing IVF between January 1999 and January 2000 participated in the cross-sectional prospective study. Patients were divided into three groups: group I, minimal/mild endometriosis (n = 12); group II, moderate/severe endometriosis (n = 10); and group III, tubal obstruction (n = 19). The ultra-short protocol was used in association with recombinant FSH for ovulation induction. Follicular fluid analysis was performed using radioimmunoassay with specific kits. RESULTS: Follicular fluid IGF-1 and IGFBP-3 levels were not significantly different among the groups; however, follicular fluid IGFBP-1 levels were lower in those patients with moderate/severe endometriosis (P < 0.05). Comparison of ovulation induction time, number of recombinant FSH units, number of follicles, oocytes and embryos, and fertilization and gestation/cycle rates showed non-significant differences. CONCLUSION: Infertile patients with moderate/severe endometriosis, which is associated with ovulatory dysfunction, presented lower levels of IGFBP-1 in the follicular fluid when undergoing IVF.

Adult↗
PubMed1996

The risk of ovarian cancer after treatment for infertility.

Recently, much attention in both the medical and lay communities has been focused on a possible association between fertility drug use and invasive ovarian cancer, and ovarian tumors of low malignant potential. A causal relationship, if shown to exist, has important implications. In the past year, several large case-control and cohort studies have attempted to address this issue. However, interpretation of the available data has been hampered by a number of factors. Retrospective study designs, small numbers of ovarian cancer cases, and inconsistent reporting of fertility drug use and type of infertility have all been common methodological shortcomings. The known ovarian cancer risk factors of low parity and infertility have been particularly difficult to separate from any effect of ovulation induction. The current epidemiologic data are insufficient to implicate conclusively specific fertility medications in ovarian carcinogenesis. The data do suggest that women with refractory infertility may constitute a high-risk population for developing ovarian cancer, independent of fertility drug use. Until the relationship between ovulation induction and ovarian cancer risk is defined more accurately, a high index of clinical suspicion for ovarian neoplasms is indicated before, during, and after treating women for infertility.

Adult↗
PubMed1982

Induction of ovulation and cyclic activity in anestrous ewes with testosterone treated wethers and ewes.

An experiment was conducted to evaluate the effectiveness of wethers and ewes treated with testosterone preparations to induce ovulation and breeding activity in anestrous ewes. The testosterone was administered three times at weekly intervals. Wethers and ewes treated with 105 mg testosterone propionate and wethers treated with 100 mg testosterone from testosterone cyclopentyl propionate were as successful as vasectomised rams in inducing ovulation and cyclic activity in ewes. Seven days after the last injection the concentrations of testosterone in peripheral bloods were not significantly different from that in the vasectomised rams. By day 28 the concentrations were significantly lower than in the rams. The testosterone preparations tested are suitable for the induction of male sexual behavior and are rapidly excreted by sheep.

Journal Article↗
PubMed2001

Effect of the total motile sperm count on the efficacy and cost-effectiveness of intrauterine insemination and in vitro fertilization.

OBJECTIVE: To determine prognostic factors for achieving a pregnancy with intrauterine insemination (IUI) and IVF. To compare the effectiveness and cost-effectiveness of IUI and IVF based on semen analysis results. DESIGN: Retrospective cohort study. SETTING: Academic university hospital-based infertility center. PATIENT(S): One thousand thirty-nine infertile couples undergoing 3,479 IUI cycles. Four hundred twenty-four infertile couples undergoing 551 IVF cycles. INTERVENTION(S): IUI and IVF treatment. MAIN OUTCOME MEASURE(S): Multiple logistic regression analysis was used to assess the significance of prognostic factors including a woman's age, gravidity, duration of infertility, diagnoses, use of ovulation induction, and sperm parameters for predicting the outcomes of clinical pregnancy and live birth rate after the first cycle of IUI and IVF. The relative effectiveness and cost-effectiveness of these treatments were then determined based on sperm count results. RESULT(S): Female age, gravidity, and use of ovulation induction were all independent factors in predicting pregnancy after IUI. The average total motile sperm count in the ejaculate was also an important factor, with a threshold value of 10 million. For IVF, only female age was an important predictor for both clinical and ongoing pregnancy. When the average total motile sperm count was under 10 million, IVF with ICSI was more cost-effective than IUI in our clinic. CONCLUSION(S): An average total motile sperm count of 10 million may be a useful threshold value for decisions about treating a couple with IUI or IVF.

Adult↗
PubMed1998

Laparoscopic surgery for heterotopic pregnancies: a case report and a brief review.

A heterotopic pregnancy is in effect a multiple pregnancy with one or more intrauterine pregnancies coexisting with an ectopic pregnancy and is rarely spontaneous. With the increasing popularity of ovulation induction performed during assisted reproductive techniques, it will not be surprising to observe that this phenomenon has increased significantly. However, diagnosis is often delayed because of its rarity and difficulty. We report a case of a woman with a viable intrauterine pregnancy who had a complication of ovarian hyper-stimulation syndrome secondary to ovulation induction following in vitro fertilization and embryo transfer, but who, during hospitalization, presented with clinically progressive abdominal pain. An unruptured ectopic pregnancy of the right fallopian tube was diagnosed accidentally by laparoscopy and laparoscopic salpingectomy was immediately performed. Post-operative follow-up revealed that the intrauterine pregnancy continued normally. She delivered a normal female baby at 38 weeks of gestation. The promising neonatal outcome might suggest that laparoscopy might be safely performed to aid differential diagnosis in an uncertain condition during pregnancy: therefore, laparoscopic surgery might be an appropriate method to manage some carefully selected patients with HP. A brief review of the published literature on the role of laparoscopy in the diagnosis and management of heterotopic pregnancy is given.

Adult↗
PubMed1996

An extended 10-day course of clomiphene citrate (CC) in women with CC-resistant ovulatory disorders.

OBJECTIVE: To evaluate the effectiveness of extended duration clomiphene citrate (CC) (100 mg for 10 days) as an alternative to complex ovulation induction strategies for women who fail to ovulate despite standard incremental doses of CC of > or = 150 mg for 5 days. DESIGN: Retrospective case series. SETTING: University-based infertility practice. PATIENT(S): Thirty women with CC-resistant World Health Organization group II ovulatory disorders. INTERVENTION(S): At least one cycle of 100 mg CC from days 3 to 12. RESULT(S): Fourteen patients (47%) ovulated during 31 of their 48 cycles (65%). Five women (17%) conceived a total of seven singleton pregnancies, including five term deliveries and two spontaneous abortions. Weight, body mass index, and the presence of hyperandrogenism did not predict responsiveness to the extended duration CC. Side effects were similar to those reported during standard CC treatment. CONCLUSION(S): An extended 10-day course of CC provides a simple, noninvasive, and inexpensive alternative for a subset of women with ovulatory disorders that are refractory to standard CC treatment.

Adult↗
PubMed2006

Polycystic ovary syndrome and metformin in pregnancy.

UNLABELLED: The diagnostic criteria of polycystic ovary syndrome incorporate hyperandrogenism, polycystic ovaries, anovulation and irregular menstrual bleeding and the syndrome is a recognized reason behind infertility. The biguanide metformin has encouraging effects on several metabolic aspects of the syndrome, including insulin sensitivity, plasma glucose concentration and lipid profile. Moreover, metformin improves the ovarian function in women diagnosed with polycystic ovary syndrome. Hence, metformin is considered an agent for ovulation induction among these patients. However, even higher ovulation frequencies have been observed when metformin has been adjuvant to clomifene therapy. Metformin-induced ovulation presumably brings about resumption of regular menstrual cycles and improved conception rates. Polycystic ovary syndrome patients are presumably more likely than healthy women to suffer from pregnancy-related problems like early pregnancy loss, gestational diabetes mellitus and hypertensive states in pregnancy. Recent data suggest sparing effects of continued metformin therapy throughout pregnancy on early pregnancy loss and gestational diabetes mellitus, but its impact on hypertensive complications to pregnancy appears less evident. Instead, metformin might even induce pre-eclampsia or exert no effect on blood pressure. CONCLUSION: So far, evidence for safety of continued therapy throughout gestation is insufficient, and existing papers are limited in design and might mask for fetal toxic outcomes due to metformin therapy. Prior to a recommendation of sustained metformin therapy throughout pregnancy, randomized placebo-controlled double-blinded clinical trials are awaited with interest, so that present assumptions on efficiency can be clarified, in order to assure efficient and safe management of pregnant polycystic ovary syndrome patients.

Drug Administration Schedule↗
PubMed1989

GnRH agonist administration in polycystic ovary syndrome.

The study was designed to examine (1) the effects of the luteinizing hormone releasing hormone (GnRH) agonist, buserelin, on pituitary and ovarian hormone secretion, and (2) the effect that pituitary-ovarian suppression with a GnRH agonist has on subsequent ovulation induction with exogenous gonadotrophins (hMG), in polycystic ovary syndrome (PCOS). Two protocols were studied where buserelin was administered intranasally to all patients in a dose of 200 micrograms, six times daily. Ten patients received buserelin until an oestrogen withdrawal bleed occurred while a further 12 patients received buserelin for 4 weeks, before hMG was co-administered. Nine of the above subjects also underwent conventional ovulation induction with hMG. Blood samples were taken daily for radioimmunoassay of LH (LH-RIA), FSH, sex steroids and inhibin and for immunoradiometric assay of LH (LH-IRMA). Following buserelin administration there was an initial rise in LH-RIA, FSH, oestradiol (E2) and inhibin (P less than 0.01). Fourteen days were needed for LH-RIA to return to the normal range, with both protocols resulting in a fall in LH-RIA and FSH (P less than 0.01) before hMG was co-administered. Twenty-eight days of buserelin administration were needed to suppress E2 into the castrate range. Inhibin and both E2 and FSH were closely correlated throughout buserelin administration (P less than 0.01). There was failure to respond to an intravenous bolus of 100 micrograms of GnRH from 7 days of buserelin administration onwards, despite the serum LH-RIA still being raised at 7 days. Serum samples assayed for LH by RIA using WHO Matched Reagents and by IRMA were closely correlated (r = 0.96, P less than 0.01). There was no difference in the proportion of ovulations (52% vs 66%) or pregnancies (1 vs 1) in the GnRH agonist or control group. Similar amounts of hMG were needed in both groups and there was multiple follicular development (greater than 3 follicles greater than 15 mm diameter; 41% vs 38%) following hMG administration. There was a close correlation between E2 and inhibin levels (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Intranasal↗
PubMed1994

Transfusion-dependent homozygous beta-thalassaemia major: successful twin pregnancy following in-vitro fertilization and tubal embryo transfer.

Homozygous beta-thalassaemia (thalassaemia major) is a severe, transfusion-dependent anaemia that also causes infertility due to endocrine impairment. Very few pregnancies are reported among such patients and there is only one report in the literature referring to a pregnancy achieved with ovulation induction and intra-uterine insemination. We report here the first successful twin pregnancy following in-vitro fertilization and tubal embryo transfer in a transfusion-dependent homozygous beta-thalassaemic woman with an oligoasthenozoospermic partner. Prior to ovarian stimulation, desferrioxamine was discontinued due to potential fetotoxicity. Pre-gestational transfusional and chelating therapies were resumed after delivery. In such patients, ovulation induction and assisted reproductive techniques appear crucial in achieving pregnancy with concurrent haematological balance without desferrioxamine administration.

Adult↗