Ovulation Induction Protocols Research Articles

Highly expressed recombinant human follicle-stimulating hormone from Chinese hamster ovary cells grown in serum-free medium and its effect on induction of folliculogenesis and ovulation

To develop efficient Chinese hamster ovary (CHO) cells that express recombinant human FSH (rhFSH) in serum-free conditions and to investigate the effect of this newly synthesized rhFSH on folliculogenesis and ovulation. Experimental study. Seoul National University, South Korea. Forty immature hypophysectomized rats and 40 androgen-sterilized mice. A stable single CHO cell that expresses rhFSH at a high level was obtained by introducing the human chorionic gonadotropin (hCG) alpha-subunit and FSH beta-subunit genes. After purification processing, we investigated the effect of this newly synthesized rhFSH on folliculogenesis in hypophysectomized rats and ovulation in androgen-sterilized mice. The ovary weight, uterine weight, number of follicles, and ovarian morphology were evaluated in immature hypophysectomized rats. The number of ovulated oocytes and ovarian morphology were examined in androgen-sterilized mice. After purification processing, we analyzed the new rhFSH using matrix-associated laser desorption ionization-time of flight and found that this new rhFSH increased both ovarian weight and uterine weight in hypophysectomized rats and induced ovulation in androgen-sterilized mice. This newly synthesized rhFSH might be safely used in anovulatory infertile woman as well as in ovulation induction protocols for subfertile women.

Evaluating the equivalence of clomiphene citrate with and without metformin in ovulation induction in PCOS patients

To evaluate the benefit of Metformin added to Clomiphene Citrate in a primary ovulation induction protocol in PCOS patients. Prospective randomised controlled study. Tygerberg Academic Hospital, Stellenbosch University and the Institute of Reproductive Medicine at Vincent Pallotti Hospital, Cape Town. 107 patients presenting with PCOS. Group A was pre-treated with metformin 850 mg twice a day for at least 6 weeks before clomiphene was added and the metformin was used throughout the study period. Group B received clomiphene without pre-treatment with metformin. In both groups clomiphene was given at a starting dose of 50 mg day 4-8 and increase with increments of 50 mg to a maximum of 150 mg if no response was achieved. The ovulation rate achieved in women in the M+C/C arm was 34/52 (65.4%) compared to 36/55 (65.5%) in the C/C arm. The treatment effect ((M+C/C) - C/C) is 0% with 95% confidence interval of -18.1% to 18%. The per protocol ovulation results were 34/42 (81%) in the M+C/C arm compared to 36/48 (75%) in the C/C arm. The ovulation rate difference was 6% with 95% confidence interval -11% to 22%. In a comparison of successful ovulating versus non-ovulating women from the trial the following were significant baseline determinants: lower median weight in the ovulating group (77 kg versus 86 kg, p = .021), lower median bmi (29.0 versus 32.9, p = .009), lower median DHEAS at baseline (4.6 compared to 7.0, p = .049), lower median 17OH-progesterone (2.2 versus 4.6, p = .027) and higher baseline median SHBG ( 37.8 compared to 28.5, p = .036). Although identical ovulation rates were observed in both arms equivalence could not be concluded with respect to the specified criteria.

Multi-nucleation of human embryos: clinical and laboratory factors in its occurrence and its impact on developmental capacity

OBJECTIVE: Multinucleation, the occurrence in embryos of blastomeres with ≥ 2 nuclei per blastomere, can be a criterion for exclusion from transfer in In Vitro Fertilization (IVF). Clinical and laboratory factors that may influence the occurrence of multinucleation were considered. DESIGN: Retrospective review of clinical profiles of patients with embryos in which 0 % (control) or ≥50% multinucleated blastomeres (MNB-emb) were identified on Day 2 of development, and the prospective study of morphology and implantation of the embryos from these two groups. MATERIALS AND METHODS: Two groups of patients in a continuous interval from January to May 2007 were studied: those having no MNB-emb (control, n=267) and at least one MNB-emb (n=206). These patients were compared for age, BMI, day 3 FSH, type of pituitary suppression and ovarian stimulation, mean estradiol (E2) at time of hCG, days of stimulation, number of eggs retrieved, and pregnancy rate. The incidence of MNB-emb was compared according to method of fertilization (insemination or ICSI), and the morphologic quality of the embryos from both groups was assessed. RESULTS: No significant differences were observed between control and MNB-emb groups with respect to age, BMI, day 3 FSH, mean E2 at hCG trigger, number of eggs or days of stimulation. Ovulation induction protocols were similar in both groups. Method of fertilization did not influence the incidence of MNB. Significantly more embryos with good morphology were found in the control compared to the MNB-emb group at day 2 (41.8% vs. 38.5, respectively, p=0.001) and day 3 (30.5% vs. 25.3%, respectively, p=0.01). While the number of embryos transferred in the MNB-emb group was significantly higher than the control (2 vs. 1.7, respectively, p=0.05), there was no difference in the implantation rates (30.3% vs. 31.2%, respectively). CONCLUSIONS: These findings demonstrate that the occurrence of embryos containing multinucleated blastomeres in a cohort does not reflect a reduced developmental capacity of the sibling non-multinucleated embryos. Further, the occurrence of MNB-embryos cannot be predicted on the basis of the patient factors or treatment cycle dynamics examined in this study, and may reflect gamete- or embryo- specific cellular deficiencies or anomalies.

Prospective randomized study to compare the effects of embryo culture performed in an incubator class 100 with HEPA VOC filter on outcome measures of ICSI cycles. Preliminary results

OBJECTIVE: Many laboratories have installed specialized incubator filtration units with the intent of enhancing air quality for embryo culture. The aim of this study is to determine whether an incubator Class 100 with HEPA VOC filter (carbon-activated) enhance the outcome measures in ICSI cycles. DESIGN: Prospective, randomized comparative study. MATERIALS AND METHODS: Prospective recruitment of all patients of age ≤ 39 years who underwent fresh ICSI cycles from September 2007 to April 2008. Fifth eight ICSI cycles were included. Embryo culture was performed either in an incubator equiped with HEPA filter (High Efficiency Particulate Air) plus carbon-activated for volatile organic compounds-HEPA VOC filter (Group I = 26) or in an identical incubator Class 100 with HEPA filter only without carbon activated (Group II = 32).Ovulation induction, laboratory techniques, embryo culture and transfer protocols were identical in both groups. Main outcome measures were number of good quality embryos transferred (≥8 cells G1/G2) and clinical pregnancy. The Student's t-test and Chi-square were applied for statistical analysis. P<.05 was considered statistically significant. RESULTS: Female age, total doses of gonadotrophins, endometrial thickness on the day of hCG administration, n° of oocytes metaphase II retrieved, n° of embryos transferred, n° of good quality embryos transferred, and clinical pregnancy were not statistically different between groups. A total of 20 transfers were performed in Group I and 28 in Group II. There were 6 cycles without transfers in Group I and 4 in Group II due to either oocyte retrieval failure or OHSS risk. Results are shown in the table 1.Table 1Patients and treatment cycles characteristicsCulture in HEPA VOC filter n=20Culture in HEPA filter n=28p valueAge32.65±3.7434.17±3.330.14Total amount of gonadotrophins (IU)1736.25±600.632011.42±789.190.19End. thickness (mm)10.39±2.1910.90±2.230.44Oocytes metaphase II (n)5.35±3.474.50±3.120.38EB transf (n)2.20±0.692.14±0.700.78EB 8C G1/G2 transf1.10±0.711.10±0.780.97Clinical pregnancy (%)55 (11/20)39 (11/28)0.38Values are expressed as mean ± SD. Open table in a new tab Values are expressed as mean ± SD. CONCLUSIONS: The preliminary data on this ongoing study has demonstrated no significant differences between the two groups in all parameters analyzed. The complete study will include 120 cycles in each group to provide 80% power in detect a difference in clinical pregnancy between the groups.

In vitro culture under physiologic oxygen concentration improves blastocyst yield and quality: a prospective randomized survey on sibling oocytes

A prospective randomized study was carried on sibling oocytes in which human gametes and embryos were cultured at physiologic (6% CO(2) + 5% O(2) + 89% N(2)) condition from insemination to day 6 or at atmospheric (6% CO(2) in air) condition until day 3 and at physiologic environment afterward. The results showed that physiologic oxygen concentration throughout culture period improved total blastocyst yield and day 5 embryo quality.

The effect of anti-thyroid antibodies on endometrial volume, embryo grade and IVF outcome

Thyroid auto-immunity (TAI) has been implicated as the most common cause of hypothyroidism in general population, especially in women. Many studies revealed that increased infertility incidences with TAI. The aim of the present article was to evaluate the effect of thyroid auto-antibody (TAA) positivity on embryological parameters, IVF-outcome and endometrial volume (EnV) in infertile patients who were applied for routine artificial reproductive technologies (ART) programme. This study included prospective, sequential, cross-sectional analyses of parameters obtained from 69 patients with unexplained infertility. It was the first ART application of patients. Patients were homogenous for age, body mass index, basal hormone measurements and underwent same ovulation induction protocol. They were evaluated for thyroid hormone profile and TAAs and divided into three groups; TAA negative group (n = 31), TAA positive group (n = 23) and TAA positive and euthyroid with medication group (n = 15). There were no differences among groups for the number of Grade-1 and Grade-2 embryos, distribution of embryo-grades, number of oocytes retrieved and fertilised, biochemical pregnancy ratios (PR), EnV and miscarriage ratio. However, the clinical PR was significantly lower in the TAA positive group (p = 0.024). In conclusion, the embryo grades and EnV did not differ among groups. But the clinical PR differs and the anti-thyroid peroxides positivity, above the cut-off point, affects the clinical PR.

Polycystic ovaries and infertility: Our experience

Polycystic ovary syndrome (PCOS) is one of the most common (15-20%) endocrine disorders in women of childbearing age. Although it is a major cause of infertility, its etiology remains unknown and its treatment difficult. To evaluate the incidence, treatment and outcome of patients with PCOS. Retrospective analysis. PCOS patients (914 of the 1057) attending the outpatient department (OPD) from June 2003 to February 2008 were evaluated for this study. Of the 914 patients investigated, 814 came for treatment and these patients were studied for hormonal disturbances and their response to various modalities of treatment. Of the 2270 infertility patients, 46.50% (1057) had PCOS, out of these, 86.47% (914) were investigated and 77% (814) came for treatment. Our overall pregnancy rate was 48.40% (394/814). The pregnancy rate per cycle with timed intercourse (TI) was 44.77% (47/105), 17.09% (286/1673) with intrauterine insemination (IUI), 29.82% (51/171) with in vitro fertilization (IVF) and 22.22% (10/45) with frozen embryo transfer (FET). The maximum number of pregnancies (85.29%, 284/333) were achieved in the first three treatment cycles. The abortion rate was 19.01% (73/384) and the incidence of ectopic pregnancy was 5.47% (21/384). Complications seen were in the form of ovarian hyperstimulation (OHSS), retention cyst on day two and multiple pregnancies in 11.71% (228/1946) of the total treatment cycles. Most PCOS symptoms could be adequately controlled or eliminated with proper diagnosis and treatment. Thus, ovulation induction (OI) protocols and treatment modalities must be balanced for optimal results.

Predictors of ovarian response: progress towards individualized treatment in ovulation induction and ovarian stimulation

Ovarian stimulation is applied in the clinic to restore mono-ovulatory cycles in anovulatory women (ovulation induction) or to induce the development of multiple dominant follicles for assisted reproduction. Ovarian response is the endocrine and follicular reaction of the ovaries to stimulation. Achieving an appropriate ovarian response to anti-estrogens or exogenous gonadotrophins is central to ovulation induction and ovarian stimulation protocols. However, achieving an adequate response, without cycle cancellation or adverse events related to under- or over-stimulation, is complicated by high intra- and inter-individual variability. To predict each patient's ovarian response to medication for ovarian stimulation and to individualize the starting dose of exogenous gonadotrophin or the need for exogenous luteinizing hormone, various clinical, endocrine, ovarian ultrasonographic and genetic characteristics have been explored. Some of these features have been incorporated into prediction models. In this review, the methodology behind predictive factors and prediction models and their potential clinical applicability across ovulation induction and ovarian stimulation are explored.

Triggering final oocyte maturation with a GnRH agonist does not affect apoptosis of follicular granulosa-lutein cells

We have shown that a low level of apoptosis of human granulosa-lutein cells (GL cells) from IVF cycles is associated with younger age and pregnancy. We would therefore expect a low level of apoptosis in egg donors. The present study was designed to test the effect of different ovulation induction protocols (antagonist/hCG, antagonist/GnRH agonist, downregulation/hCG) on in vitro GL cells apoptosis in young donors. We were particularly interested in whether administration of a GnRH agonist to trigger final oocyte maturation instead of hCG in the antagonist group would increase the rate of in vitro apoptosis of gonadotropin-exposed GL cells. In vitro assays. 19 egg donors with a mean age of 22.42 ± 2.87 underwent ovulation induction with recombinant FSH combined with recombinant LH or HMG using a downregulation or an antagonist protocol. The ovarian response was monitored by transvaginal ultrasound and blood estradiol levels as needed. Final oocyte maturation was triggered by either hCG or leuprolide acetate and the egg retrieval was performed 35.5 hours later. GL cells were collected from pooled follicular fluid after oocyte recovery. Cells were washed and further purified using a 50% percoll gradient and anti-CD45 coated magnetic beads. After 48 hour culture without serum the percentage of apoptosis was determined under a fluorescent microscope after staining with 10 μM caspACE FITC-VAD-FMK (a fluorescent marker for activated caspases) and 0.05 mg/ml propidium iodide. Statistical analysis was carried out using the Student's t-test. Overall the apoptosis rate was low, as expected for a group of young donors (19.06% ± 4.01, n = 19). There were no significant differences in the percentage of apoptosis among the three groups of egg donors analyzed (antagonist/hCG: 17.35 ± 4.64, n = 5; antagonist/GnRH agonist 19.55 ± 2.61, n = 5; downregulation/hCG: 19.73 ± 4.42, n = 9; P>0.05). Moreover, the level of apoptosis observed in the donors was significantly lower than that observed in a group of infertility patients with a mean age of 32.47 ± 3.22 undergoing IVF during the same period of time (19.06% ± 4.01, n = 19 vs. 24.92 ± 4.25, n = 19; P<0.05). Triggering of ovulation with a GnRH agonist does not increase apoptosis of gonadotrophin exposed granulosa-lutein cells. Furthermore, there is no difference between downregulation and antagonist protocols.

Ovulation induction protocol using equine chorionic gonadotropin and porcine luteinizing hormone in the weaned sow

Objective: To determine the lowest dose of porcine luteinizing hormone (pLH) that induces ovulation in a predictable manner in mixed-parity sows 80 hours after treatment with equine chorionic gonadotropin (eCG) at weaning. Materials and methods: All sows were injected intramuscularly (IM) with 600 IU eCG at weaning. At 80 hours post weaning, sows were treated IM with pLH at doses of 0.625 mg (n = 5), 1.25 mg (n = 14), 2.5Â mg (n = 21), and 5.0 mg (n = 5). The 15 controls were untreated. Approximate time of ovulation was determined using transrectal realtime ultrasound 8 hours before and 16 hours post pLH injection, and thereafter at 8-hour intervals until ovulation was confirmed. Results: Administration of pLH was effective in inducing ovulation in weaned sows. The pLH-to-ovulation interval was shorter in sows given pLH at 1.25 mg (P &lt; .05), 2.5 mg (P &lt; .01), and 5.0 mg (P &lt; .05) than in controls. Variance associated with the pLH-to-ovulation interval tended to be less in treated than in control sows (P &lt; .10). More sows administered either 2.5 or 5.0 mg pLH ovulated by 40 hours post pLH administration than all other treatments (P &lt; .01). Implications: Doses of 2.5 and 5.0 mg of pLH did not differ in their effect of inducing ovulation in an estrus-synchronization program initiated with 600 IU of eCG at weaning. Controlling the time of ovulation allows insemination to occur at the time of optimal fertilization.

Comparison of Crinone 8% intravaginal gel and intramuscular progesterone supplementation for in vitro fertilization/embryo transfer in women under age 40: interim analysis of a prospective randomized trial

This study was performed to compare the efficacy of Crinone 8% intravaginal gel and intramuscular progesterone (IMP) supplementation for luteal phase support in women under age 40 undergoing IVF-ET. Results of the interim analysis of this rigorously designed prospective randomized controlled study are presented. Pregnancy rates, implantation rates, and early spontaneous abortion rates were similar for patients receiving Crinone or IMP, whereas fewer side effects and greater overall satisfaction were reported by women receiving Crinone.

Age-Specific Levels for Basal Follicle-Stimulating Hormone Assessment of Ovarian Function

Traditionally, the most important measurement in the assessment of ovarian function has been age-independent baseline follicle-stimulating hormone (FSH) levels. The objective of this study was to characterize the continuum of ovarian function based on age-specific categories of baseline FSH. In a cross-sectional historical cohort study we evaluated records of 434 patients with baseline FSH levels of less than 12 milli international units/mL that underwent ovulation induction for in vitro fertilization (IVF) with long gonadotropin-releasing hormone (GnRH) antagonist or GnRH agonist suppression and modal gonadotropin stimulation of 300 units of gonadotropins per day. In these patients with apparent normal ovarian function by current baseline FSH criteria and with routine ovarian stimulation, we assessed IVF cycle outcomes, including oocyte yields, based on age-specific baseline FSH levels, defined as levels less than or equal to the 95% confidence interval for each age group. Age-specific baseline FSH levels predicted the retrieval of fewer than or equal to four oocytes, with a positive predictive value of 19.5% and a negative predictive value of 88%. The Mantel-Haenszel common odds ratio for fewer than or equal to 4 oocyte production in the presence of premature ovarian aging was 2.8 (95% confidence interval 1.52-5.17; P<.001). These results suggest that, within generally accepted normal baseline FSH values, women with baseline FSH above the 95% confidence limits for age produce fewer oocytes in response to normal ovulation induction protocols compared with other women their age.

Ageing and reproduction: is polycystic ovary syndrome an exception?

Background Polycystic ovary syndrome (PCOS) is a frequent cause of infertility. Despite an impressive number of reports, few have evaluated the influence of age upon fertility. We present the outcomes of three infertile women with PCOS who achieved spontaneous pregnancies when ageing. Case reports Three patients with PCOS were monitored for more than 20 years. PCOS was confirmed by clinical data (oligo/amenorrhoea, infertility, hirsutism), hormonal measures and ovarian ultrasonography. All three infertile patients were treated for several years using numerous ovulation induction protocols with varying responses. When ageing, they gained more regular cycles and spontaneously became pregnant at 39, 40 1/2 and 36 years of age, more than 5 years after induction treatment was stopped, and in spite of increasing weight in each of them. Conclusions These clinical observations suggest improved fertility in some PCOS ageing women. The positive impact of ageing on cycle regularisation in PCOS has recently been claimed but the fertility outcome was not evaluated. Ovary ageing results in diminution of the follicular cohort in both normal and PCOS women, associated with decreased inhibin B and anti-müllerian hormone (AMH) levels. Lower inhibin B levels induce FSH enhancement, with a rise in FSH rate per follicle which may determine better follicle maturation, regular and ovulatory cycles in PCOS ageing women. The best proof of this improved fertility was the occurrence of spontaneous pregnancies which never occurred previously.

Understanding the role of LH: myths and facts

This review summarizes a series of lectures given at a recent Continuing Medical Education meeting in Hamburg, Germany (May 2007), aiming to understand the role of luteinizing hormone (LH) in follicular development during the natural menstrual cycle and controlled ovarian stimulation. Clinical situations and target groups of patients who might benefit from LH supplementation during their ovarian stimulation were discussed and defined. The lectures updated knowledge on the physiology of LH during the normal menstrual cycle and the role of LH in ovarian stimulation. The concept of the ‘LH window’ was presented, and the use of LH supplementation in different groups of patients undergoing controlled ovarian stimulation was discussed, including those with advanced age, hypogonadotrophic hypogonadism, pituitary down-regulation and poor response. In addition, the different ways of using LH or human chorionic gonadotrophin supplementation in ovulation induction protocols were described.

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

To compare the ovarian and endometrial effects of anastrozole and clomiphene when used with gonadotropins in a combination protocol. Prospective randomized trial. Academic infertility center. Fifty infertile women. 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. Ovarian follicle number and size, E(2) levels, endometrial thickness, pregnancy, and cancellation rates. 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. 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.

P-240: Evaluation of two incubation environment Class 100 versus Class 100 000 on intracytoplasmic spem injection (ICSI) cycles outcome

The aim of our study was to evaluate the impact of two different incubation environments: Class 100 x Class 100 000 on embryo quality and pregnancy rate. Retrospective observational study. One hundred twenty-three consecutive intracytoplasmic sperm injection (ICSI) cycles were studied from January 2004 to November 2005. Cycles were divided in two groups: in group I (60 cycles), the embryo culture was performed in an incubator without Hepa filter air flow system and as a consequence the incubator air was similar to the ambient air classified as Class 100 000. In group II (63 cycles), the embryo culture was performed in a incubator with Hepa filtered air flow system which continuously filtered the entire chamber volume every 60 seconds and a class 100 air quality was achieved, within 5 minutes of the door closing. Ovulation induction, laboratory techniques, embryo culture and transfer protocols were identical in both groups. Embryologists and physicians performing procedure in both periods were unaltered. Main outcome measures were: normal fertilization and cleavage rates, number of good quality embryos (8 cells or more/ grade 1 or 2) available for transfer, number of good quality embryos transferred (grades 1 or 2) and clinical pregnancy. Female age, duration of stimulation, total doses of gonadotrophins, endometrial thickness on the day of hCG administration, number of oocytes metaphase II retrieved per cycle, number of good quality embryos available for transfer, number of good quality embryos transferred, fertilization rate, cleavage rate and clinical pregnancy were not statistically different between groups.Main results are shown in the table 1. Values are expressed as mean ± SD. The t-test was used to compare variables.Tabled 1 Our study demonstrated that incubation environment Class 100 000 is as good when compared with incubation environment as Class 100 in relation to the parameters analysed. Although some papers concluded that fertilization and cleavage rates, quality of embryos transferred and clinical pregnancies are improved in an environment with high-quality air, we have acknowledged that there is a need for appropriately designed prospective randomized studies to demonstrate the real impact of the high-quality air (Class 100) on human in vitro fertilization outcome.

P-50: How does the number of oocytes retrived affect the outcome in ART?

The aim of this study was to determine the suitable range of oocytes retrieved that would yield high pregnancy rates. Retrospective observational study. In a retrospective study we analysed 438 ICSI cycles that resulted in a total of 3575 oocytes retrieved from January 2000 to December 2005. The cycles were stratified into four ranges according to the number of oocytes retrieved. Group 1: 1 to 3 oocytes (n=75); group 2: 4 to 6 oocytes (n=125); group 3: 7 to 10 oocytes (n=111) and group 4: more than 11 oocytes (n=127). Ovulation induction, laboratory techniques, embryo culture and transfer protocols were identical in all groups. Main outcome measures were age, total doses of gonadotrophins, number of oocytes metaphase II retrieved, total number of embryos available for transfer, total number of good quality embryos (grades 1 or 2) transferred, fertilization rate and pregnancy diagnosed by a positive hCG serum test at least 14 days after the transfer. Values were expressed as mean ± SD. ANOVA and Fisher exact tests were used. The mean female age and the total doses of gonadotrophins were significantly higher in groups 1 and 2 compared to groups 3 and 4. The fertilization rate was significantly higher in group 1 compared to groups 2, 3 and 4. The lower number of oocytes retrieved was associated with a significant decline in the number of oocytes metaphase II and good quality embryos transferred. Group 1 had a statistically significant reduction in pregnancy rates when compared to the others. However, no significant differences were found in pregnancy rates among groups 2, 3 and 4, despite the fact that more embryos had been tranferred in the groups 3 and 4 compared to group 2 (table 1).Tabled 1 The retrieval of at least 4-6 oocytes per patient is reasonable to maximize the satisfactory rates in patients undergoing ICSI cycles. This should be taken into account when counseling poor responding patients regardless of woman’s age.Tabled 1

P-751: The effectiveness of clomiphene citrate in suppressing the LH surge in the minimal stimulation IVF protocol

The commonly used ovulation induction protocol for IVF at present is the combined use of GnRHa, HMG and HCG. This protocol, however, is accompanied by various complications, such as the ovarian hyperstimulation syndrome, increased costs for the therapy, and certain risks, including the increased incidence of multiple pregnancies. Although IVF protocol utilizing the natural ovulation cycle is the least onerous therapy for patients, it entails the possible loss of the optimal oocyte retrieval timing because the LH surge is not controlled.

Improved monofollicular ovulation in anovulatory or oligo-ovulatory women after a low-dose step-up protocol with weekly increments of 25 international units of follicle-stimulating hormone

To compare the effectiveness and efficiency of two low-dose step-up protocols for ovulation induction in women with anovulatory infertility (World Health Organization group II). Open-label, prospective, randomized, group-comparative, multicenter study. Eighteen infertility centers in Europe and Canada. One hundred fifty-eight anovulatory or oligo-ovulatory infertile women. Patients were randomly assigned to one of two protocols for one cycle of follitropin beta (rFSH) using a pen device. The starting dosage was 50 IU/day for 7 days. In the absence of follicles > or =12 mm, the daily dosage was increased by either 25 or 50 IU per week. The percentage of all subjects treated who ovulated after one treatment cycle (efficacy) and the total rFSH dose to reach ovulation (efficiency). The 25-IU group had a higher incidence of monofollicular growth (41.3% of 80 vs. 21.8% of 78 women) and ovulation (81.3% vs. 60.3%), a lower cumulative rFSH dose (887 IU vs. 984 IU), and fewer cancellations due to hyperresponse (>3 follicles > or =15 mm; 5.0% vs. 20.5%). Both protocols were well tolerated. Weekly increments of 25 IU in the daily dose were more effective and efficient than 50-IU increments.

Similar ovulation rates, but different follicular development with highly purified menotrophin compared with recombinant FSH in WHO Group II anovulatory infertility: a randomized controlled study

The contribution of the LH activity in menotrophin preparations for ovulation induction has been investigated in small trials conducted versus FSH preparations. The objective of this study was to demonstrate non-inferiority of highly purified urinary menotrophin (HP-HMG) versus recombinant FSH (rFSH) with respect to the primary outcome measure, ovulation rate. This was a randomized, open-label, assessor-blind, multinational study. Women with anovulatory infertility WHO Group II and resistant to clomiphene citrate were randomized (computer-generated list) to stimulation with HP-HMG (n=91) or rFSH (n=93) using a low-dose step-up protocol. The ovulation rate was 85.7% with HP-HMG and 85.5% with rFSH (per-protocol population), and non-inferiority was demonstrated. Significantly fewer intermediate-sized follicles were observed in the HP-HMG group (P<0.05). The singleton live birth rate was comparable between the two groups. The frequency of ovarian hyperstimulation syndrome and/or cancellation due to excessive response was 2.2% with HP-HMG and 9.8% with rFSH (P=0.058). Stimulation with HP-HMG is associated with ovulation rates at least as good as a rFSH in anovulatory WHO Group II women. LH activity modifies follicular development so that fewer intermediate-sized follicles develop. This could have a positive impact on the safety of ovulation induction protocols.