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PubMed1999

Ovulation induction with low dose alternate day recombinant follicle stimulating hormone (Puregon).

We investigated whether a recombinant follicle stimulating hormone (FSH) (Puregon) can be administered less frequently and at lower doses during ovulation induction than is current practice. Patients (20-35 years, body mass index <30 kg/m(2)) with infertility and chronic anovulation secondary to polycystic ovarian syndrome and resistant to previous clomiphene treatment received (Puregon); 100 IU, n = 17 patients, or 50 IU, n = 10 patients) on alternate days. After 2 weeks and in the absence of follicular recruitment, doses were increased stepwise at weekly intervals (50 IU/alternate days). Twenty-two cycles out of 27 were ovulatory. There were six pregnancies, five from Puregon (100 IU) and one from Puregon (50 IU); four pregnancies proceeded to term. The duration of stimulation (mean, range) with Puregon (100 IU) was 16.4, 7-29 and Puregon (50 IU) 19.1, 8-38 days. The gonadotrophin doses administered (mean; range) were 689, 200-1800 IU (Puregon 50 IU) and 939, 400-2300 IU (Puregon 100 IU). We conclude that low dose alternate day Puregon treatment is suitable for this difficult patient group.

Adult↗
PubMed1990

A novel regimen of gonadotropin-releasing hormone (GnRH) antagonist plus pulsatile GnRH: controlled restoration of gonadotropin secretion and ovulation induction.

Using a primate model, we have tested a novel regimen of gonadotropin-releasing hormone (GnRH) antagonist plus pulsatile GnRH for the achievement of controlled restoration of gonadotropin secretion and ovulation induction. As a prelude, ovariectomized cynomolgus monkeys (n = 3) were treated with Antide ([N-Ac-D-Nal(2)1, D-pCl-Phe2, D-Pal(3)3, Lys(Nic)5, D-Lys(Nic)6, Lys(iPr)8, D-Ala10]-GnRH) (3 mg/kg per day) for 6 consecutive days. On the 7th day, pulsatile GnRH therapy was initiated in a 7 day-on: 7 day-off regimen for a total of four exposures. Next, four intact monkeys were given Antide to suppress ovarian function (estradiol less than 10 pg/mL) followed by pulsatile GnRH. In the ovariectomized monkeys, Antide-induced suppression of gonadotropin concentrations was reversed by the pulsatile GnRH so that follicle-stimulating hormone concentrations were completely normalized and luteinizing hormone concentrations were returned to within the lower range (+/- 2 SD) of the pretreatment mean. The abruptness of the onset or loss of gonadotropin secretion was precisely synchronized with the weekly on and off phases of the GnRH pulse regimen. In intact monkeys, ovarian steroid secretions were abruptly subdued and then successfully re-established by pulsatile GnRH in the face of sustained circulating levels of Antide. Thus, we conclude that our primate model of combination therapy, GnRH antagonist plus pulsatile GnRH, establishes the possibility of a new clinical treatment regimen for patients desiring relief from the sequelae of hyperandrogenemia (polycystic ovarian disease) and ovulatory dysfunction.

Animals↗
PubMed2002

Comparison of short and long ovulation induction protocols used in ART applications according to the ovarian response and outcome of pregnancy.

This retrospective study was designed to determine whether there is any difference between short and long protocol ovulation induction with Gonadotropin Releasing Hormone agonist (GnRHa) and gonadotropins used in Assisted Reproductive Technology (ART) applications according to the number of retrieved oocytes, oocyte maturity, fertilization rates, embryo quality and the outcome of pregnancies. 240 cycles consisting of in vitro fertilization (IVF) cycles without andrologic factor and intracytoplasmic sperm injection (ICSI) cycles were evaluated. 112 cycles which were induced by short protocol GnRHa and Follicle Stimulating Hormone (FSH) + Human Menopausal Gonadotropin (HMG) combinations and 128 cycles which were induced by long protocol GnRHa and FSH + HMG combinations were compared according to the number of retrieved oocytes, cancellation rate of cycles, oocyte maturity, fertilization rates, embryo quality and pregnancy rates. The cancellation rate for short protocol cycles were found to be significantly higher than those with long protocol. The number of retrieved oocytes, mature oocytes and fertilized oocytes were also found significantly lower. The quality of embryos did not show any significant difference between these groups. The clinical pregnancy rates were evidently found to be high in the long protocol cycles. As a conclusion we have found that while the number of retrieved oocytes, mature oocytes, fertilized oocytes and clinical pregnancy rates were increasing, the cancellation rate of cycles were decreasing significantly in ART cycles induced by long protocol.

Cell Count↗
PubMed1994

Ovulation induction with gonadotropins and intrauterine insemination compared with in vitro fertilization and no therapy: a prospective, nonrandomized, cohort study and meta-analysis.

OBJECTIVES: To determine whether one to four cycles of ovulation induction with hMG and IUI or one cycle of IVF results in the highest pregnancy rate and is least expensive and whether published pregnancy rates for one to four cycles of hMG and IUI results in a higher pregnancy rate than rates for one cycle of IVF, zygote intrafallopian transfer (ZIFT), or GIFT. DESIGN: Prospective, nonrandomized, cohort study. Patients were excluded who were infertile for < 18 months, had a significant male factor, had greater than mild endometriosis, or had bilateral nonpatency of the fallopian tubes. Cohort groups included 47 hMG and IUI patients (99 cycles), 19 IVF patients (19 cycles), and 21 patients (210 cycles) receiving no treatment. A meta-analysis on accumulated hMG and IUI data using similar entry criteria was also performed. Theoretical calculations were performed and stable fecundity assumed to compare with national data on IVF, ZIFT, and GIFT. SETTING: Fertility Center, Division of Reproductive Endocrinology, University of Utah, Salt Lake City, Utah. RESULTS: A course of therapy with one to four cycles of hMG and IUI was just as effective as one cycle of IVF in achieving pregnancy. No significant difference in pregnancy rates was found between one IVF cycle and one to four cycles of hMG and IUI in our population. In vitro fertilization was more expensive than four cycles of hMG and IUI. Both IVF and hMG and IUI were more effective than no therapy. Published data also suggest that four cycles of hMG and IUI theoretically result in higher pregnancy rates than one cycle of IVF, ZIFT, or GIFT. CONCLUSION: Cost-benefit analysis comparing hMG and IUI, IVF, and no therapy in infertility patients may favor a course of four cycles of hMG and IUI as the first line of therapy. Using meta-analysis and theoretical assumptions, the pregnancy rate for one cycle of hMG and IUI is inferior to IVF, GIFT, or ZIFT; two cycles are comparable to IVF or ZIFT and inferior to GIFT; three cycles are superior to IVF or ZIFT and comparable to GIFT; and four cycles are theoretically superior to all techniques.

Adult↗
PubMed2006

Patient experience with follitropin alfa prefilled pen versus previously used injectable gonadotropins for ovulation induction in oligoanovulatory women.

OBJECTIVE: To evaluate patient satisfaction with the follitropin alfa prefilled pen (Gonal-f RFF Pen), compared with previously used injectable gonadotropins (vial/ampoules and syringe), in women undergoing ovulation induction (OI). RESEARCH DESIGN AND METHODS: Women aged 18-40 years undergoing OI for oligoanovulatory infertility were enrolled from nine US fertility centers in this prospective, open-label clinical trial. Participants received recombinant follitropin alfa using a prefilled pen. Patient satisfaction was determined using a pre-treatment questionnaire to assess gonadotropin treatments undertaken within 6 months of study initiation and an in-treatment questionnaire to assess satisfaction with the prefilled pen. MAIN OUTCOME MEASURES: The primary endpoint was the proportion of patients who preferred the prefilled pen compared to previous injectable gonadotropin therapies. Efficacy and safety were also assessed. RESULTS: Seventy-three subjects were screened for the study; 62 enrolled, were treated with the follitropin alfa pre-filled pen, and 61 completed the in-treatment questionnaire. Sixty-one of 61 patients who stated a preference preferred the prefilled pen to previous injectable gonadotropin therapies (61/61; 100%; 95% confidence interval: [94.1-100.0%]). One patient did not state a preference. Of these 61 patients, 54 (89%) found that the prefilled pen instructions were easy to understand compared to 17 of 59 (29%) who thought instructions for the conventional syringes were easy to understand. When preparing their dose, significantly fewer patients contacted their healthcare provider two or more times during the treatment cycle when receiving treatment with the prefilled pen (2/61, 3%) than during the first treatment cycle with prior gonadotropin treatment, 11/59 (19%, p = 0.007). The pen interfered slightly or not at all with patients' normal daily activities in 61 of 61 patients (100%) versus 50 of 59 patients (85%) who had this opinion regarding injections during their prior treatment cycles (p = 0.003). All 61 patients who stated a method of injection preference found the prefilled pen less stressful to use than syringes and would recommend the pen to another woman considering gonadotropin treatment. A total of 10/62 (16%) subjects reported 18 treatment-emergent adverse events (AEs). Two cases of ovarian hyperstimulation syndrome occurred post-treatment and one serious AE occurred (post-treatment ectopic pregnancy). Injection site reactions were generally mild to moderate, with mild itching (6 patients, 9.7%) and moderate redness in one patient. Fifteen patients reported mild redness (24.2%). Mild bruising (21.0%), mild pain (33.9%), and mild burning (32.3%) were also reported by patients. Seven patients (11.3%) had moderate pain. CONCLUSIONS: In this open-label, non-comparative study, patients undergoing OI preferred administering gonadotropins using the follitropin alfa prefilled pen compared to their prior use of vials/ampoules and a syringe. Patients using the prefilled pen found it less stressful, easier to use and more convenient than a conventional syringe and would recommend the pen to another woman considering gonadotropin treatment.

Adult↗
PubMed2004

Evaluation of a pen device for self-administration of recombinant human FSH in clomiphene citrate-resistant anovulatory women undergoing ovulation induction.

This open-label multicentre study evaluated ease of use, safety, and efficacy of a pen device for self-administration of recombinant follicle-stimulating hormone (rFSH) in 43 subjects undergoing ovulation induction. Follitropin beta was administered subcutaneously with the Follistim Pen within 3 days of onset of menses. A 75 IU starting dose could be increased by 25 or 50 IU on days 8 and 15 if no ovarian response was observed. Human chorionic gonadotrophin (HCG; 10,000 IU) was administered when one follicle > or =18 mm or two to three follicles > or =15 mm were observed. Subjects received standardized instruction for the pen device and subject comprehension was recorded as subjects practised and prepared injections. Ease of use was also evaluated by questionnaire. Forty-four subjects enrolled; 43 were treated with rFSH and 41 were treated with HCG. The comprehension questionnaire revealed that during the mock injection, 100% of subjects properly loaded the cartridge into the pen device, while 95% selected the correct dose and 100% self-injected the medication prescribed. During the second actual injection, 100% of subjects comprehended these pen-related steps. The ease-of-use questionnaire showed that 100% of the subjects rated the overall experience of self-administering with the pen as 'very good' to 'good'. Mean duration and total amount of follitropin beta were 11.4 +/- 4.2 days and 1070.3 +/- 580.3 IU respectively. Ovulation rate was 95%. Biochemical and ongoing pregnancy rates per attempt were 34.9 and 30.2% respectively. Three subjects experienced serious adverse events [asthma; ovarian hyperstimulation syndrome (OHSS) and pain; OHSS]. In conclusion, the pen device provides an easy, safe, and effective way for women to self-administer follitropin beta during ovarian stimulation.

Adult↗
PubMed2003

Poor response to ovulation induction is a stronger predictor of early menopause than elevated basal FSH: a life table analysis.

BACKGROUND: During the course of assisted reproduction treatment, a number of women exhibit a "poor response" to ovulation induction, or demonstrate an elevated basal FSH level (> or =10 IU/l) at a young age. We sought to determine whether these women are at increased risk of early menopause and poor reproductive performance. METHODS: A retrospective cohort study included 118 "poor responders" with normal basal FSH level (<10 IU/l), 164 women with raised basal FSH (> or =10 IU/l), and 265 controls, who underwent assisted reproduction treatment between 1987 and 1998. All women were < 40 years of age at the time of treatment and had normal menstrual cycles. Participants were sent a postal questionnaire in 2000-2001, seeking information on ovarian function and reproductive performance following cessation of treatment. RESULTS: After adjusting for age and smoking habits, women with poor response and raised basal FSH levels were more likely to experience symptoms of the peri-menopause [hazard ratios 2.4, 95% confidence interval (CI) 1.52-3.78, and 2.76, 95% CI 1.78-4.29 respectively, P = 0.0001]. Poor responders were six times and 23 times more likely to experience the menopause within 10 years of treatment than those with raised basal FSH levels and controls respectively (hazard ratio 5.97 and 23.9, P = 0.015 and 0.002 respectively). Poor responders and those with raised basal FSH levels have half the chance of spontaneous conception after discontinuation of treatment compared with controls (P < 0.007). CONCLUSIONS: Both poor response to ovarian stimulation and raised basal FSH are markers of reduced ovarian reserve and predict an increased risk of early menopause.

Adult↗
PubMed2006

Basal ovarian cysts and clomiphene citrate ovulation induction cycles.

OBJECTIVE: To evaluate the effect of simple basal ovarian cysts in patients undergoing infertility treatment with clomiphene citrate. To evaluate the effect of clomiphene citrate on pretreatment simple ovarian cysts. METHODS: Prospective cohort trial of 84 infertility patients undergoing ovulation induction with clomiphene citrate. Patients with basal ovarian cysts of 10 mm or greater (n = 42) were compared with patients without ovarian cysts (n = 42). The main outcome measure was ovulation determined by menstrual cycle day 21 progesterone level. Each patients with an ovarian cyst was also evaluated for persistence or resolution of the cyst in association with ovulation and cyst size. Pretreatment and posttreatment transvaginal ultrasound examinations were performed on all patients. RESULTS: Demographic data were similar among the groups. The mean ovarian cyst size was 17.4 +/- 5.8 mm. Patients in the ovarian cyst group were significantly less likely to ovulate (80.9% versus 97.6%, P < .05), but did not differ in pregnancy rate compared with patients without baseline ovarian cysts (4.8% versus 11.9%, P = .43). Persistent ovarian cysts occurred in 36.7% of the patients. The initial size of the cyst did not predict cyst persistence. CONCLUSION: According to these data, basal ovarian cysts significantly reduce ovulatory events in patients treated with clomiphene citrate. LEVEL OF EVIDENCE: II-2.

Adult↗
PubMed1990

Transvaginal ultrasonic needle guided aspiration of pelvic inflammatory cystic masses before ovulation induction for in vitro fertilization.

Transvaginal aspiration of pelvic cystic inflammatory masses guided by a real time ultrasound vaginal transducer is described. The technique was successfully used in 32 patients to aspirate these masses before ovulation induction for in vitro fertilization (IVF). It is a safe and simple procedure that resulted in significantly higher ovarian response to stimulation for IVF, easier ultrasonic follow-up of the follicles, significant increase in the average number of oocytes per pick-up, and significant increase in the number of embryos per transfer when compared with the control group.

Adult↗
PubMed2002

Intracardiac thrombosis and fever possibly triggered by ovulation induction in a patient with antiphospholipid antibodies.

We report on a 28-year old patient with polycystic ovary syndrome (PCOS) who presented with fever and laboratory markers of inflammation. Her medical history was relevant for multiple ovulation inductions (OI) and ovarian hyperstimulation syndrome (OHSS). She had two miscarriages and one preterm delivery. Intracardiac thrombosis was diagnosed in the presence of antiphospholipid antibodies. We suggest that primary antiphospholipid syndrome (APS) was possibly triggered by OI.

Adult↗
PubMed1996

The effect of sperm-mucus interaction test on the outcome of in vitro fertilization and ovulation induction combined with intrauterin insemination.

OBJECTIVE: To investigate the effect of sperm mucus penetration tests (SPT) on the fertilization rate (FR) and pregnancy rate (PR) in patients treated with either in vitro fertilization (IVF) or ovulation induction combined with intrauterine insemination (OI + IUI). METHODS: Retrospective analysis of a regional Infertility Unit database. Infertile couples where the women had normal ovarian function and a normal pelvis at laparoscopy and her partner had normal seminology who had failed at least two SPTs who were treated with either IVF or OI + IUI. These patients were compared with similar couples in whom SPTs were satisfactory (SPT + ve). Group A (SPT + ve) consisted of 46 patients who underwent 78 treatment cycles of IVF and Group B (SPT - ve) comprised 31 patients who underwent 35 IVF cycles. Group C (SPT + ve) consisted of 39 patients who underwent 84 treatment cycles with OI + IUI, and Group D (SPT - ve) consisted of 15 patients who underwent 37 cycles with the same treatment. RESULTS: In patients treated with IVF, the FR and PR per embryo transfer were 77.0% and 20.0%, respectively in Group A, and 64.0% and 22.6%, respectively in Group B. The differences in FRs were statistically significant (p < 0.001) but there was no difference in the PRs. In patients treated with OI + IUI, the PR per cycle were 22.0% in Group C and 16.2% in Group D. CONCLUSION: The results indicate that SPT failure was associated with a lower FR in IVF but this did not affect the PRs. Similarly there was no difference in PRs following OI + IUI.

Adult↗
PubMed1984

Advanced endometrial maturation after ovulation induction with human menopausal gonadotropin/human chorionic gonadotropin for in vitro fertilization.

Endometrial biopsy was performed between the first and third luteal phase day in 22 normally cycling patients following human menopausal gonadotropin and human chorionic gonadotropin ovulation induction for in vitro fertilization but in whom embryo transfer was not accomplished. Eleven patients showed an "advanced" pattern and 10 an "in-phase" endometrium according to the Noyes criteria. A significant difference in serum progesterone levels on days 16 and 18 was found in these two groups. Serum progesterone levels were significantly higher by day 18 if pregnancy was established. In in vitro fertilization and embryo transfer the embryo arrives 24 to 48 hours earlier than in natural conception in the endometrial cavity. Therefore, the "advanced" endometrium may have some benefit for embryo implantation.

Biopsy↗
PubMed1975

Plasma estrogen monitoring of ovulation induction.

Eight hMG-hCG therapy cycles in 6 anovulatory infertile patients are presented. Daily plasma estrogen monitoring during the therapy contributed to success in inducing ovulation in all 6, 3 of whom established pregnancies and delivered healthy babies. The duration of hMG therapy required varies among individuals. Duration and dosage can be determined on the basis of daily plasma estrogen levels. Administration hCG is recommended to trigger ovulation when these levels reach 300 to 600 pg/ml. Although success in ovulation induction and pregnancy is achievable, multiple ovulation and multiple pregnancy cannot be predicted or prevented.

Adult↗
PubMed1988

Treatment-independent pregnancies after cessation of gonadotropin ovulation induction in women with oligomenorrhea and anovulatory menses.

Life-table analysis was performed for the cumulative spontaneous pregnancy rate (CSPR) of 56 patients with oligomenorrhea and anovulatory cycles who had been treated with gonadotropin for ovulation induction between 1963 and 1985. Twenty-seven had at least one spontaneous pregnancy, giving rise to a CSPR of 66.4% (95% confidence limit [CL] 42.4% to 90.4%) at 115 months for the first spontaneous pregnancy, which is significantly lower than the cumulative induced pregnancy rate (CIPR) of 88.6% at 23 months for the first course of gonadotropin therapy (P less than 0.0001). This fertility potential was not affected by the baseline estrogen and follicle-stimulating hormone levels, diagnosis, result of gonadotropin therapy, and age and menstrual pattern during exposure to spontaneous pregnancy by Cox regression analysis. More multiple births occurred in the induced pregnancies than in the spontaneous pregnancies (P = 0.005).

Anovulation↗
PubMed1997

The predictive value of the sperm-cervical mucus interaction test on the outcome of in vitro fertilization and ovulation induction combined with intrauterine insemination.

We investigated the effect of the sperm-cervical mucus penetration tests (SPT) on the fertilization rate (FR) and pregnancy rate (PR) in patients treated with either in vitro fertilization (IVF) or ovulation induction combined with intrauterine insemination (OI + IUI). Infertile couples where the women had normal ovarian function and a normal pelvis at laparoscopy and her partner had normal seminology who had failed at least 2 SPTs were treated with either IVF or OI + IUI. These patients were compared with similar couples in whom SPTs were satisfactory (SPT/ve). Group A (SPT+ve) consisted of 46 patients who underwent 78 treatment cycles of IVF and Group B (SPT-ve) comprised 31 patients who underwent 35 IVF cycles. Group C (SPT/ve) consisted of 39 patients who underwent 84 treatment cycles with OI + IUI, and Group D (SPT-ve) consisted of 15 patients who underwent 37 cycles with the same treatment. In patients treated with IVF, the FR and PR per embryo transfer were 77.0% and 20.0% respectively in Group A, and 64.0% and 22.6% respectively in Group B. The difference in FRs was statistically significant (p > 0.001) but there was no difference in the PRs. In patients treated with OI + IUI, the PR per cycle were 22.0% in Group C and 16.2% in Group D. These results indicate that SPT failure was associated with a lower FR in IVF but this did not affect the PRs. Similarly there was no difference in PRs following OI + IUI.

Female↗
PubMed2005

[Catastrophic antiphospholipid syndrome after ovulation induction].

INTRODUCTION: The catastrophic antiphospholipid syndrome (CAPS) is a rare expression of the antiphospholipid syndrome (APLS). The all predicting factors of happening of CAPS are not yet discovered. Some women presenting an APLS with infertility have recourse to ovulation induction (OI). EXEGESIS: After an OI, a woman is admitted for acute renal failure, hypertension, seizures, respiratory failure. History and immunologic tests are in favour of APLS. Renal biopsy highlights a thrombotic microangiopathy. Diagnosis of CAPS is made. Patient improves after respiratory assistance, parenteral treatment for hypertension and anticoagulant therapy. CONCLUSION: IO seems to be on of the factors which leads to CAPS. To avoid such consequences, it's essential to know the history and the immunological status of the patients having recourse to this treatment to take care of these risked pregnancies.

Acute Disease↗
PubMed1988

Characterization of recombinant DNA derived-human luteinizing hormone in vitro and in vivo. Efficacy in ovulation induction and corpus luteum support.

The present data are the first, to our knowledge, to demonstrate the production feasibility of a commercially available medication of pure human luteinizing hormone from recombinant DNA technology (rechLH). The rechLH preparation achieved ovulation induction and corpus luteum support in the primate menstrual cycle. The observations described herein indicate the opportunity for significant improvement in the treatment of infertile women and men who require gonadal stimulation. Recombinant DNA-derived gonadotropin products, rechLH in this case, will have several therapeutic advantages compared with current medications extracted from urine. These advantages include (1) better reliability of an available supply of hormone and (2) improved treatment flexibility in determining the optimal dose ratio of follicle-stimulating hormone and luteinizing hormone or avoidance of the long-acting effects of human chorionic gonadotropin, as the needs of individual patients may dictate.

Animals↗
PubMed1993

The value of transabdominal pelvic ultrasonography in monitoring of ovulation induction with gonadotropins.

Seventy-five patients with a total of 306 human menopausal gonadotropin treatment cycles over the period 1984-1989 were analysed retrospectively to evaluate the value of transabdominal pelvic ultrasonography in prevention of complications arising from ovulation induction with human menopausal gonadotropins. There were 60 pregnancies giving a pregnancy rate of 19.6% per cycle. There was positive correlation between the number of follicles > or = 14 mm in mean diameter and the incidence and degree of hyperstimulation (p < 0.005) as well as the incidence of multiple pregnancies (p < 0.01). Ultrasonography is a useful adjunct for monitoring in such a program.

Adult↗