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Objective To assess the effect of altering the timing of hCG administration on ongoing pregnancy rates in patients stimulated with recombinant FSH (rec-FSH) and GnRH antagonists for IVF. Design Prospective, randomized, controlled trial. Setting Tertiary referral center. Patient(s) Four hundred thirteen patients undergoing IVF. Intervention(s) Rec-FSH stimulation starting on day 2 of the cycle combined with daily GnRH antagonist starting on day 6 of stimulation. Patients were randomized to receive 10,000 IU of hCG either as soon as at least three follicles were ≥17 mm on ultrasound (early-hCG group, 208 patients) or 2 days later after this criterion was met (late-hCG group, 205 patients). Main outcome measure(s) Ongoing pregnancy rate. Result(s) Fertilization rates and number and quality of embryos transferred did not differ between the two groups. However, a significantly lower ongoing pregnancy rate was present in the late-hCG as compared with the early-hCG group (25.0% vs. 35.6%, respectively). Conclusion(s) Prolongation of the follicular phase in patients stimulated with rec-FSH and GnRH antagonists for IVF does not affect oocyte or embryo quality but is associated with a significantly lower ongoing pregnancy rate.

This study addresses the role of cAMP hydrolytic isoenzyme phosphodiesterase type 3 (PDE 3) modulation on human oocyte maturation in vitro. Presence of phosphodiesterase type 3 A (PDE 3A) mRNA was confirmed in human germinal vesicle-stage (GV) oocytes. Making use of a selective PDE 3 inhibitor, Org 9935 (10 μM), oocytes retrieved from immature follicles were arrested in prophase I with a high efficiency for up to 72 h. Cumulus oocyte complexes (COCs) were retrieved in the follicular phase of the cycle before or after exposure to endogenous LH or hCG administration in vivo and randomly distributed into maturation medium with or without the PDE 3 inhibitor. Previous exposure of small follicles to LH activity in vivo had no influence on the arresting capacity of the PDE 3 inhibitor. Reversal from pharmacological arrest leads to a progression through meiosis in a normal time frame with formation of a well-aligned metaphase plate. Ultrastructure analysis of COC derived from follicles between 8 and 12 mm showed that the induced extension of prophase I arrest in vitro resulted in cytoplasm changes but not in apparent nuclear changes during culture.

BACKGROUND: A pen device, similar to an insulin pen, has been recently marketed for the administration of follitropin b in cartridges. A randomized controlled trial was performed to compare the efficacy and convenience of this pen device delivering follitropin b with a conventional syringe delivering follitropin a. METHODS: A total of 200 patients needing IVF/ICSI treatment and willing to self-inject were enrolled in the study. All subjects had ovarian stimulation according to a long protocol and were randomized to the pen or the conventional syringe group during down-regulation by means of a computer-generated randomization list using random numbers. Patients were asked to fill in a daily local tolerance book after each injection. On the day of hCG the patients scored a Visual Analogue Scale (VAS) for pain and convenience. RESULTS: The average duration, total dose of recombinant FSH and number of cumulus oocyte complexes retrieved were 10.8/12.0 days (P = 0.001), 1880/2226 IU (P < 0.001) and 15.2/13.1 respectively in the pen device and conventional syringe groups; the presence of pain after the daily injection was significantly higher in the conventional syringe group (P = 0.027); the visual analogue scale score was similar for pain but significantly more convenient for the pen device (P < 0.001). The live birth rate per embryo transfer was 32.9 and 34.4% respectively in the pen device and conventional syringe groups. CONCLUSIONS: Self-injection with the pen device is safe and easy, more convenient and less painful for the patient, requires less FSH and shortens the treatment duration.

To investigate the effect of ovarian stimulation on integrin expression in the early luteal phase.Seven endometrial biopsies were taken 2 days after the oocyte retrieval from stimulated cycles for IVF and 23 from natural cycles, 2 days after ovulation.Endometrium was in-phase in 22/23 and 7/7 biopsies from the natural and stimulated cycles, respectively. Integrins alpha(1) and alpha(4) were simultaneously positive in 43.4% from the natural and in all (100%) the stimulated cycles (P0.03). On the day of the endometrial biopsy, progesterone serum values were higher in the stimulated cycles (55.2+/-9.5 microg/l versus 8.5+/-3.8 microg/l) (P0.001). HSCORE value was significantly higher in stimulated cycles for both integrins.Endometrial integrin expression is more consistently present in the early luteal phase in stimulated cycles than in natural cycles and this may be related to the higher serum progesterone concentration and/or the more advanced endometrial histological features.

Objective To compare ongoing implantation rates under two different GnRH antagonist protocols. Design Randomized controlled trial. Setting Tertiary referral center. Patient(s) One hundred eleven women undergoing ovarian stimulation for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Intervention(s) Ovarian stimulation with 150 IU recombinant-FSH (rec-FSH) starting on day 2 of the cycle and GnRH antagonist starting either on day 6 of stimulation (fixed group) or when a follicle of ≥15 mm was present after at least 5 days of stimulation (flexible group). In the flexible group, the rec-FSH dose was increased to 250 IU when the antagonist was initiated. Main outcome measure(s) Ongoing implantation and pregnancy rate. Result(s) In patients with no follicle of ≥15 mm present on day 6 of stimulation, a significantly lower ongoing implantation rate was observed if the flexible scheme was applied as compared with the fixed scheme of administration (8.8% vs. 23.9%, respectively). Exposure of the genital tract to LH or E 2 from initiation of stimulation to antagonist administration was able to distinguish between pregnant and nonpregnant patients in the population studied. Conclusion(s) High exposure of the genital tract to LH and E 2 in the early follicular phase is associated with a reduced chance of pregnancy in cycles stimulated with recombinant FSH and GnRH antagonist for IVF/ICSI.

The purpose of this prospective study was to assess the reproductive outcome of patients with polycystic ovarian syndrome (PCOS) treated by in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) with recombinant FSH (rFSH) and gonadotrophin releasing hormone (GnRH) antagonists. One hundred and ten patients were evaluated. The starting dose of rFSH was 100 IU in 67 women with body mass index (BMI) 29 kg/m(2). GnRH antagonist was started by the detection of a follicle of a 15mm in ultrasound scan. A significantly lower ongoing pregnancy rate per oocyte retrieval (25.6% versus 46.7%, P = 0.04) and a higher occurrence of ovarian hyperstimulation syndrome (16.3% versus 3.0%, P = 0.03) was observed in the group of patients with BMI >29 kg/m(2) as compared with the group of patients with BMI 29 kg/m(2) in whom stimulation is initiated with 200 IU of rFSH as compared with PCOS patients with BMI

The objective of this prospective study was to assess the relationship of LH and oestradiol on day 7 of the cycle in patients stimulated with recombinant FSH (rec-FSH) for IVF before initiation of gonadotrophin-releasing hormone (GnRH) antagonist. One hundred and forty-six women treated for IVF using GnRH antagonists for premature LH rise suppression were stimulated with 150 IU of rec-FSH from day 2 to day 6 of the cycle. On cycle day 7, LH concentrations (median 1.8, range 0.1-7.51) were positively associated with oestradiol concentrations on the same day by multiple regression analysis controlling for patient's age, concentrations of FSH and LH on cycle day 2, FSH concentrations on cycle day 7 and follicular index on cycle day 7. In conclusion, the higher the endogenous unsuppressed LH concentrations on day 7 of the cycle after 5 days of stimulation with rec-FSH for IVF, the higher the serum oestradiol concentrations on the same day.

Objective: To assess the effect of ovarian stimulation with recombinant FSH, GnRH antagonists, and hCG on endometrial maturation on the day of oocyte pick-up. Design: Prospective study. Setting: Tertiary referral center. Patient(s): Fifty-five women undergoing controlled ovarian hyperstimulation for IVF/intracytoplasmic sperm injection (ICSI). Intervention(s): [1] Ovarian stimulation with recombinant FSH, starting on day 2 of the cycle and GnRH antagonist, starting after a median of 6 days of recombinant FSH stimulation (range, 5–12 days); [2] hCG administration for ovulation induction; and [3] aspirational biopsy of endometrium at oocyte pick-up. Main Outcome Measure(s): Endometrial histology at oocyte pick-up by Noyes criteria. Result(s): Advancement of endometrial maturation (2.5 ± 0.1 days) as compared to the expected chronological date was observed in all antagonist cycles at oocyte retrieval. Endometrial advancement at oocyte pick-up increased in line with values of LH at initiation of stimulation and the duration of recombinant FSH treatment before the antagonist was started. Conclusion(s): The higher the values of LH at initiation of stimulation and the longer the duration of recombinant FSH treatment before the antagonist is started, the more advanced the endometrial maturation at oocyte pick-up.

The luteal phase has been found to be defective in virtually all the stimulation protocols used in in-vitro fertilization (IVF), indicating that common mechanisms might be involved despite the use of different drugs. A normal luteal phase is characterised by a normal hormonal environment, normal progesterone secretion by the corpus luteum and adequate endometrial secretory transformation. Luteinizing hormone supports the corpus luteum and luteal luteinizing hormone (LH) levels have been found to be reduced in human menopausal gonadotrophin (HMG), gonadotrophin-releasing hormone (GnRH)-agonist/HMG and GnRH-antagonist/HMG protocols, probably leading to an insufficient corpus luteum function. Supraphysiological steroid serum concentrations routinely observed in stimulated cycles may adversely affect LH secretion and induce a luteal-phase defect. In turn, these high steroid serum concentrations may advance early luteal-phase endometrial development leading to embryo-endometrial asynchrony and decreased pregnancy rates in IVF cycles.

One to three per cent of infertile women develop severe ovarian hyperstimulation syndrome after superovulation for assisted reproduction treatment (ART). This severe complication can be avoided when oocytes are obtained at an immature stage (germinal vesicle stage) out of small or medium-sized follicles. This hypothesis has been tested in several infertile women, but clinical pregnancies are disappointlingly low. This new approach in ART is still at an experimental phase and this treatment has still to be improved before routine clinical application. Experimental work in animals and humans suggest a beneficial effect in providing a short preliminary pretreatment with follicle-stimulating hormone to select for a developing cohort of follicles. The aspiration of oocyte cumulus complexes is carried out with a short needle applying reduced aspiration pressure. A crucial point is to provide the appropriate culture environment for the immature oocytes. An optimal cumulus-enclosed human oocyte culture system needs to be defined. The composition of the culture medium could be suggested by in vitro work carried out in animal models. As developmental competence is established during the latest phases of oocyte growth and is dependent on the storage of RNA, a prolonged in vitro maturation period (before inducing nuclear maturation) could provide the necessary transcriptional and translational changes. The conditions to achieve this improved cytoplasmic maturation by prolonging the in vitro culture remain to be defined. More objective noninvasive parameters for oocyte maturity are also needed to pursue research in this field.

Objective: To summarize data from completed phase II and III clinical trials on children born after controlled ovarian stimulation using the luteinizing hormone–releasing hormone antagonist cetrorelix. Design: All children born after ovarian stimulation in patients treated for infertility who were in prospective studies until March 23, 1999. Setting: Academic research center. Patient(s): Children born after IVF or IVF plus ICSI. Intervention(s): Controlled ovarian stimulation with cetrorelix in a multiple-dose or single/dual-dose protocol. Main Outcome Measure(s): Outcome of pregnancy and, in deliveries, the date of birth, number and sex of children born, birth weight, body length, and abnormalities were recorded. At approximately 1 year of age and 2 years of age, body weight and length and abnormalities in physical and mental development were recorded. Result(s): Two hundred nine and 18 children were born after fresh and frozen embryo transfers, respectively. Of the pregnancies, 76.2% (179 of 234) resulted in live birth and ectopic pregnancy occurred in 3.4% (8 of 231); one heterotopic pregnancy and four induced abortions were recorded. The malformation rate among all live births, stillbirths, and aborted fetuses was 3.1%. Conclusion(s): Use of cetrorelix in controlled ovarian stimulation does not harm the subsequently born children.

A total of 346 women with normal ovulatory function was stimulated with human menopausal gonadotrophins (HMG) to attain ovarian stimulation for IVF or intracytoplasmic sperm injection (ICSI). Stimulation with HMG started on cycle day 2 or 3. After 6 days of stimulation, Cetrorelix in its minimum effective multiple dose of 0. 25 mg/day, was administered daily until induction of ovulation. In total, 333 patients (96.2%) reached the day of HCG administration, and 324 (93.6%) underwent oocyte retrieval. A mean of 25.2 ampoules of HMG was applied for a mean of 10.4 days. Cetrorelix was administered for a mean time lapse of 5.7 days. The mean normal fertilization rate was 60% in the IVF group and 59% in the ICSI group. Seventy pregnancies were attained, reflecting an ongoing clinical pregnancy rate of 24% per transfer. The ongoing clinical implantation rate was 11.4%. Only three cases of raised luteinizing hormone (LH) (>/=10 IU/l) with increased progesterone secretion (>/=1 ng/ml) were observed after initiation of Cetrorelix administration, reflecting an incidence of premature luteinization of 0.9%. The abortion rate was 17%. The incidence of severe ovarian hyperstimulation syndrome (World Health Organization grade III) was as low as 0.6%.

In this prospective and randomized study, 188 patients received the luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix, and 85 patients the LHRH agonist buserelin to prevent endogenous luteinizing hormone (LH) surges during ovarian stimulation in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Ultimately, 181 patients (96.3%) in the cetrorelix group, and 77 (90.6%) in the buserelin group, reached the day of the human chorionic gonadotrophin (HCG) injection. The mean number of human menopausal gonadotrophin (HMG) ampoules administered and the mean number of stimulation days with HMG were significantly less in the cetrorelix group than in the buserelin group (P < 0.01). A rise in LH and progesterone concentrations was observed in three of the 188 patients (1.6%) who received cetrorelix. On the day of the HCG administration, more follicles of a small diameter (11-14 mm) were observed in the buserelin group than in the cetrorelix group (P = 0. 02) and the mean serum oestradiol concentration was significantly higher in patients who received buserelin than in those who received cetrorelix (P < 0.01). Similar results were observed in fertilization, cleavage and pregnancy rates in the two groups. In conclusion, the use of the LHRH antagonists might be considered more advantageous because of the short-term application needed to inhibit gonadotrophin secretion, so allowing a reduction in the treatment time in a clinically significant manner.

The luteal phase hormonal profile and the clinical outcome of 69 patients undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) after ovarian stimulation with human menopausal gonadotrophin (HMG) and the gonadotrophin-releasing hormone (GnRH) antagonist Cetrorelix were analysed. Twenty-four patients received Cetrorelix 0.5 mg (group I) while in 45 patients Cetrorelix 0.25 mg was administered (group II). Human chorionic gonadotrophin (HCG) was used as luteal support. Nine clinical pregnancies were obtained in group I (37.5%) and 12 in group II (26. 6%). These results were not significantly different. Serum progesterone and oestradiol concentrations did not differ between the two groups either in pregnant or non-pregnant patients. An expected decrease of the same hormones was observed 8 days after the pre-ovulatory HCG injection in non-pregnant women. With regard to serum luteinizing hormone concentrations, a decrease was observed 2 days after the pre-ovulatory HCG injection and was maintained at almost undetectable levels throughout the entire luteal phase in both conception and non-conception cycles of group I and group II. This study demonstrates that different doses of GnRH antagonist do not have any impact on the luteal phase of IVF/ICSI cycles when hormonal support is given.

A 36-year-old single woman presented at the out-patient clinic in March 2000 requesting donor insemination. Between May 2000 and May 2001 she underwent six cycles of intrauterine insemination with donor sperm after clomiphene citrate stimulation without achieving a pregnancy. In January 2002, ICSI was performed; two embryos were transferred on day 3 and a dizygotic bichorionic pregnancy was achieved, which ended in a miscarriage at 21 weeks of gestation. After a second unsuccessful ICSI attempt in which a single embryo transfer was performed, she embarked upon her third attempt in March 2003 at 39 years of age. Two blastocysts were transferred after ICSI, resulting in a quintuplet gestation consisting of a monochorionic biamniotic pregnancy and a monochorionic triamniotic pregnancy. The current case report indicates that monozygotic pregnancies consisting of both twins and triplets are possible after treatment by assisted reproductive technologies. An association between extended culture, manipulation of the zona pellucida, ovarian stimulation and occurrence of monozygotic pregnancies has been suggested by retrospective studies. However, in order to identify more reliably predictive factors for the occurrence of monozygotic pregnancies, it is necessary to perform prospective trials. Hum Reprod

Objective: To evaluate the effect of supernumerary preovulatory follicular reduction as an approach to avoid multiple pregnancies in ovulation induction or superovulation cycles. Design: Retrospective study. Setting: Tertiary referral center. Patient(s): In 26 cycles, 24 patients underwent ovulation induction or superovulation with either clomiphene citrate or hMG. Intervention(s): Selective follicle aspiration was performed before hCG administration. Main Outcome Measure(s): Clinical pregnancy rate and numbers of multiple pregnancies. Result(s): A mean number of 4.5 follicles with a diameter ≥15 mm and a mean number of 4.5 follicles with a diameter ≤14 mm were observed before hCG administration. A mean number of 2.3 follicles with a diameter ≥15 mm and a mean number of 1.8 follicles with a diameter ≤14 mm were aspirated before the hCG administration. Seven singleton pregnancies (26.9% per cycle) ensued from the treatment. Conclusion(s): Aspiration of supernumerary follicles after ovulation induction or superovulation seems to be a valid approach to avoid multiple pregnancies without affecting pregnancy rate.

The development of immature oocyte collection techniques for in-vitro maturation (IVM), combined with novel culture techniques, opens new possibilities for assisted reproductive technology. Optimization of clinical management of IVM cycles will enhance pregnancy outcome, so that IVM might become an effective alternative assisted reproduction treatment for infertile patients irrespective of the cause of infertility. Parameters such as age and baseline antral follicular count are predictive of outcome and should be used as selection criteria for IVM treatment. Women with polycystic ovary disease and normo-ovulatory patients at risk of developing ovarian hyperstimulation syndrome might benefit from earlier retrieval of oocytes followed by IVM and embryo transfer. HCG priming before oocyte retrieval seems beneficial in terms of oocyte yield and maturational competence, and may increase the harvest of mature oocytes and lead to better endometrial synchronization with the developing embryo. The timing of aspiration may be crucial in IVM and selection criteria for follicle size at aspiration need defining prospectively for infertility type. Finer calibre aspiration needles and low aspiration pressure yield more oocytes. A combination of natural cycle IVF with IVM is a promising, mild and inexpensive assisted reproduction treatment, widely accessible the infertile population.

Clomiphene citrate treatment with the association of gonadotrophins and the GnRH antagonist cetrorelix 0.25mg was analysed in two different stimulation protocols for IVF. In protocol I, 18 patients were sequentially stimulated with clomiphene citrate and gonadotrophins. In protocol II, 28 patients started the gonadotrophin injections during the clomiphene citrate administration. LH values significantly dropped after the first 0.25 mg cetrorelix injection in both protocols. A total of 22% and 7% of cycles were cancelled in protocols I and II, respectively, because of poor follicular development. The clinical pregnancy rate following embryo transfer was 18.1% in protocol I and 29.1% in protocol II. In two (11.1%) cycles stimulated according to protocol I and in eight (28.5%) cycles from protocol II, premature LH surges occurred. In patients with premature LH surge, significantly fewer metaphase II oocytes were obtained. The clinical pregnancy rate following embryo transfer was 12.5% in patients with surge compared with 29.6% in patients without. LH values were lower before HCG injection in patients who achieved pregnancy in the study cycle. In conclusion, sequential clomiphene citrate and gonadotrophin administration is not recommended for clomiphene citrate/gonadotrophin/cetrorelix 0.25 cycles. Cetrorelix 0.25 mg/day was associated with a high incidence of premature LH surges and premature LH surges were associated with an adverse cycle outcome.

This study addresses the role of cAMP hydrolytic isoenzyme phosphodiesterase type 3 (PDE 3) modulation on human oocyte maturation in vitro. Presence of phosphodiesterase type 3 A (PDE 3A) mRNA was confirmed in human germinal vesicle-stage (GV) oocytes. Making use of a selective PDE 3 inhibitor, Org 9935 (10 microM), oocytes retrieved from immature follicles were arrested in prophase I with a high efficiency for up to 72 h. Cumulus oocyte complexes (COCs) were retrieved in the follicular phase of the cycle before or after exposure to endogenous LH or hCG administration in vivo and randomly distributed into maturation medium with or without the PDE 3 inhibitor. Previous exposure of small follicles to LH activity in vivo had no influence on the arresting capacity of the PDE 3 inhibitor. Reversal from pharmacological arrest leads to a progression through meiosis in a normal time frame with formation of a well-aligned metaphase plate. Ultrastructure analysis of COC derived from follicles between 8 and 12 mm showed that the induced extension of prophase I arrest in vitro resulted in cytoplasm changes but not in apparent nuclear changes during culture.

The major risks of exogenous gonadotrophin therapy for ovulation induction in a patient with polycystic ovaries (PCO) are multiple pregnancies and ovarian hyperstimulation syndrome (OHSS). This case report describes a 23-year-old patient, who was referred to the Centre for Reproductive Medicine in Brussels because of a high risk of developing OHSS and rising LH following ovulation induction with a low-dose step-up protocol using gonadotrophins. After counselling the patient, the decision was made to perform a rescue IVF cycle. The patient was first coasted with 0.25 mg ganirelix; the serum oestradiol concentrations decreased and the LH peak was successfully suppressed. No OHSS occurred. An ongoing twin pregnancy was achieved after the transfer of two embryos. This case report demonstrates the feasibility of coasting with LH-releasing hormone (LHRH) antagonists (0.25 mg ganirelix) and the usefulness of the antagonists for ovulation induction cycles in patients who need rescue IVF.

Objective: To compare ICSI with IVF using two insemination concentrations in moderate male infertility and to compare these data with other randomized controlled trials (RCTs). Design: Prospective, randomized, controlled trial and meta-analysis. Setting: University-based tertiary referral center. Patient(s): Seventy-three couples undergoing ART. Intervention(s): In one IVF group a standard insemination concentration of 0.2 × 10 6 /mL was used, whereas in the other group a high insemination concentration (HIC) of 0.8 × 10 6 /mL was used. Each protocol was compared with ICSI on sibling oocytes. Main Outcome Measure(s): Fertilization, fertilization failure, and embryonic development. Result(s): The overall fertilization rate was significantly lower after standard IVF than after ICSI: 37.4% vs. 64.3%. Where HIC IVF was used, the overall fertilization rate was not significantly different from that after ICSI: 59.6% vs. 67.6%. Eight randomized controlled trials were selected and reviewed together with the present randomized controlled trial by meta-analysis. The risk ratio for an oocyte to become fertilized was 1.9 (95% confidence interval of 1.4 to 2.5) in favor of ICSI, and 3.1 ICSI cycles may be needed to avoid one complete fertilization failure after conventional IVF (95% CI of 1.7 to 12.4). Conclusion(s): The data from this study and the meta-analysis show that ICSI is a more efficient technique in terms of fertilization, but not in comparison with HIC IVF.

Cetrorelix was administered in differing daily dosages for controlled ovarian stimulation. The dosage levels were 3 mg (9 cycles), 1 mg (19 cycles), 0.5 mg (43 cycles), 0.25 mg (46 cycles) and 0.1 mg (7 cycles). In the 3 mg, 1 mg and 0.5 mg group the respective median plasma concentrations of cetrorelix on the day of oocyte pick-up (OPU) were 2.10 ng/ml, 1.42 ng/ml and 0.88 ng/ml and 1.03 ng/ml, 0.46 ng/ml and 0.49 ng/ml on the day of embryo transfer (ET). In the 0.25 mg and 0.1 mg groups plasma cetrorelix levels were below the limit of quantification. The cetrorelix concentrations in follicular fluid (FF) in the 0.25 mg group were detec- table in only 14 out of 44 samples, while in the 0.1 mg group no detectable concentrations could be obtained. We also examined 80 cycles after single doses of 5 mg (7 cycles), 3 mg (42 cycles), and 2 mg (31 cycles) cetro-relix. On the day of OPU the respective median plasma concentrations of cetrorelix were 0.57 ng/ml, 0.62 ng/ml, and 0.56 ng/ml, and 0.61 ng/ml and 0.28 ng/ml on the day of ET in the 5 mg and 3 mg groups. In the 2 mg group, the plasma concentrations fell to below limits of quantification in 8/9 samples on the day of ET. In 26 out of 27 FF samples cetrorelix was detectable in the 3 mg single dose group (median level: 0.69 ng/ml).

Objective: To analyze the luteal phase of six patients undergoing controlled ovarian hyperstimulation (COH) with hMG and a new GnRH antagonist, Cetrorelix, without receiving luteal phase supplementation. Design: Phase II study involving the first six patients who did not receive luteal phase support. Setting: Tertiary referral center. Patient(s): Six healthy women undergoing COH for assisted reproductive techniques. Intervention(s): Oocyte retrieval was performed 36 hours after hCG administration, followed by embryo transfer 2 days later. No luteal phase supplementation was given. Main Outcome Measure(s): Serum E 2 , progesterone, LH, and FSH concentrations were measured. Result(s): The length of the luteal phase was ≤12 days in three of the six patients. One of the patients in whom the luteal phase was >12 days had a low serum progesterone concentration (2.9 ng/mL) on day 10. Serum LH concentrations decreased after the preovulatory hCG injection in all patients. However, a progressive increase in LH was observed after day 7, reaching normal values. Conclusion(s): Corpus luteum function seems to be impaired in cycles that are stimulated with hMG and the GnRH antagonist Cetrorelix.

Objective: To assess the minimal effective dose of a GnRH antagonist (Cetrorelix; Asta Medical, Frankfurt, Germany) to prevent premature LH surge in patients undergoing controlled ovarian hyperstimulation (COH) for assisted reproductive technologies. Design: In 69 patients COH was carried out with the association of hMG, starting on day 2 of the menstrual cycle, and a GnRH antagonist (Cetrorelix) was administered from day 6 of the hMG treatment (day 7 of the menstrual cycle) every day up to and including the last day of the hMG injection. In 32 and 30 patients, 0.5 mg and 0.25 mg of Cetrorelix were administered, respectively. Seven patients received 0.1 mg of Cetrorelix. Setting: Tertiary referral center. Result(s): No premature endogenous LH surge occurred in patients treated with 0.5 and 0.25 mg of Cetrorelix, and serum LH concentrations were maintained constantly low during the entire follicular phase in both groups. Follicle-stimulating hormone, LH, E 2 , and P expressed as area under the curve were similar in both groups. A premature LH surge (18 mIU/mL; conversion factor to SI unit, 1.00) with a concomitant P rise (1.7 μg/L; conversion factor to SI unit, 3.180) occurred in one of the seven patients treated with 0.1 mg Cetrorelix; therefore, treatment with this dose was discontinued. Conclusion(s): The minimal effective dose of Cetrorelix able to prevent premature LH surge in COH cycles is 0.25 mg administered daily.

We report a case of an allergic reaction to i.m. injections of urinary human menopausal gonadotrophin (HMG) and a successful management of the problem by using recombinant follicle stimulating hormone (rFSH) administered i.m. The patient underwent two zygote intra-Fallopian transfer (ZIFT) cycles, in which ovarian stimulation was carried out by a combination of gonadotrophin-releasing hormone agonist (GnRHa) and HMG. A twin pregnancy was achieved after the first cycle. The patient delivered two premature boys at 28 weeks one of whom died after 25 days from severe respiratory distress. During the second ZIFT cycle the patient developed an allergic reaction with redness and swelling in many parts of her body 30 min after every HMG injection. Despite the allergic reaction, the cycle was completed with a second ZIFT. No pregnancy was achieved in this cycle. The patient came back to our centre for a third attempt during which ovarian stimulation was accomplished with a combination of GnRHa and rFSH. Adverse reaction as well as general discomfort were not reported by the patient during ovarian stimulation with rFSH. A successful singleton pregnancy was achieved after intrauterine embryo transfer with the birth of a healthy girl after 38 weeks. If any allergic reaction is present after injection of HMG it is advisable to stimulate a subsequent cycle with rFSH.

The aim of this study was to compare the implantation rate of tubal-replaced microinjected oocytes (MIFT) versus conventional day 2 intrauterine embryo transfer in patients undergoing intracytoplasmic sperm injection (ICSI). Sixty-three patients in need of ICSI, between 18 and 37 years of age with normal menstrual cycles and fewer than four previous ICSI attempts, were randomized between April 1999 and December 2001. In the MIFT group, up to three micro-injected oocytes were transferred laparoscopically 4 h after microinjection. In the ICSI-embryo transfer group, up to three cleaving embryos were replaced into the uterine cavity 48 h after insemination. Fifty-nine patients reached the stage of oocyte retrieval; 31 patients had a day 2 embryo transfer and 28 patients had MIFT. The ongoing clinical pregnancy and implantation rate (i.e. the total number of gestational sacs with fetal heartbeat divided by the total number of transferred embryos or micro-injected oocytes) was 35 and 24% in the ICSI-embryo transfer group and 29 and 11% in the MIFT group respectively. In conclusion, this study shows a significant decrease in implantation rate in the MIFT group (P < 0.05). In this group of patients there seems to be no advantage to tubal replacement of micro-injected oocytes.