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Report of four donor-recipient oocyte cryopreservation cycles resulting in high pregnancy and implantation rates.

OBJECTIVE: To determine the clinical potential of donor-oocyte cryopreservation and thaw techniques for recipient patients. DESIGN: Institutional review board-approved prospective study of donor oocyte cryopreservation. SETTING: A large, private infertility center. PATIENT(S): Four anonymous oocyte donors underwent ovarian hyperstimulation for the purpose of oocyte retrieval and cryopreservation. The oocytes were subsequently thawed, fertilized, and transferred to 4 recipient patients. INTERVENTION(S): Oocytes were obtained from young donor patients and were cryopreserved with a slow freeze/rapid thaw protocol in which 1,2-propanediol (PrOH) and sucrose were used as cryoprotectants. Oocytes that survived were inseminated using intracytoplasmic sperm injection (ICSI). Resulting embryos were replaced into the recipient patients on the third day post-insemination. MAIN OUTCOME MEASURE(S): Post-thaw survival rate, fertilization rate, cleavage rate, implantation and clinical pregnancy rates. RESULT(S): A total of 79 metaphase II oocytes were frozen, stored frozen overnight in liquid nitrogen, and then thawed. The post-thaw survival rate was 86.1%. Normal fertilization following ICSI occurred in 89.7% of the surviving oocytes. Cleavage was observed in 91.8% of normally fertilized oocytes. A total of 23 embryos were transferred to 4 recipient patients. A clinical pregnancy rate of 75% and an implantation rate of 26.1% were achieved. CONCLUSION(S): Human oocyte cryopreservation is an effective technique that can be applied in clinical situations with high oocyte survival and clinical pregnancy rates expected.

Adult↗

Clinical outcome of cryopreserved human pronuclear stage embryos resulting from intracytoplasmic sperm injection.

OBJECTIVE: To compare the survival rate and pregnancy rate (PR) of embryos from intracytoplasmic sperm injection (ICSI) or conventional IVF, which were cryopreserved at the pronuclear stage in cycles where fresh transfer was deferred. DESIGN: Comparative observational study. SETTING: University-associated IVF center. PATIENT(S): Ninety-nine patients who deferred ET and had all their embryos cryopreserved at the pronuclear stage after 153 oocyte retrievals. Thirty-nine patients had their oocytes inseminated by ICSI and 60 patients had conventional IVF insemination. INTERVENTION(S): All embryos were frozen-thawed at the two pronuclear stage and allowed to cleave for 2 days before transfer. MAIN OUTCOME MEASURE(S): Survival rate (morphologically intact after thaw), cleavage rate (cleaved by time of transfer), and the clinical PR after frozen ET. RESULT(S): In the ICSI group, 205 embryos were thawed for use in 57 frozen ETs; in the IVF group, there were 527 embryos thawed for use in 149 frozen ETs. There was no significant difference in any of the outcome measures by insemination method: survival rates (ICSI, 93.2%; IVF, 94.8%); cleavage rates (ICSI, 95.2%; IVF, 94.7%), and clinical PR (ICSI, 14.0%; IVF, 17.4%). CONCLUSION(S): Pronuclear embryos resulting from ICSI can be cryopreserved successfully, thawed, and the survival rate and PR are comparable to conventional IVF.

Adult↗

Evidence from a salvaged treatment cycle supports an aetiology for the empty follicle syndrome that is related to terminal follicular developmental events.

Oocyte retrieval in a stimulated in-vitro fertilization treatment cycle was unsuccessful when inadvertently carried out 12 h after the administration of human chorionic gonadotrophin (HCG) injection. Repeat follicular aspiration at 36 h post-HCG injection recovered 20 oocytes, out of which 16 metaphase-II eggs were subjected to intracytoplasmic sperm injection and eight became fertilized. Uterine transfer of three cleaving embryos resulted in a singleton pregnancy which went to term and a healthy female infant was delivered. Our experience shows that in addition to issues of HCG bioavailability to the developing follicles, the temporal relationship between HCG administration (or the luteinizing hormone surge) and follicular aspiration is also an important consideration in the determination of the aetiology of the empty follicle syndrome.

Embryo Transfer↗

Ovarian stimulation for assisted reproduction with HMG and concomitant midcycle administration of the GnRH antagonist cetrorelix according to the multiple dose protocol: a prospective uncontrolled phase III study.

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%.

Dose-Response Relationship, Drug↗

Safety of drugs used in assisted reproduction techniques.

Infertility may affect one in six couples; however, the development of the assisted reproduction technique (ART) created the opportunity for a large proportion of the infertile population to bear children. Pharmacological agents are routinely used in ART, and new ones are introduced regularly, with the aim of retrieving multiple oocytes to increase the prospect of pregnancy. The combinations of drugs that are used have specific adverse effects, but it is mostly the combined action of more than one agent that causes the greatest concern. The matter is complicated by the suspicion that some techniques in ART, for example intracytoplasmic sperm injection for severe male infertility problems (including azoospermia), may also contribute to the increase in adverse effects, especially congenital malformation. Gonadotropin releasing hormone (GnRH) agonists are widely used in controlled ovarian hyperstimulation. It may give rise to a short period of estradiol withdrawal symptoms and it may also lead to luteal phase deficiency. Similarly GnRHa antagonists, which have been recently introduced to control ovarian hyperstimulation, can lead to luteal phase deficiency and may cause some local injection site reactions. The more pure form of gonadotropin leads to less local injection site reactions and their main adverse effects are associated with the consequences of multiple ovulations. It has been proposed that gonadotropins may be a factor in the increasing risk of ovarian cancer and possibly breast cancer, but this has not been substantiated. Prion infection is another potential hazard, although no cases have been reported. Ovarian hyperstimulation syndrome is a well recognised complication of controlled ovarian hyperstimulation in ART. It is usually a result of recruitment of a large number of ovarian follicles. Efforts to minimise the incidence of this syndrome and its severity are now well developed. Congenital malformations are another possible adverse effect of fertility drugs, but it is more probable that the increase in congenital abnormality that is reported in ART is because of the population studied, i.e. patients already at high risk of congenital malformation, rather than the fertility drugs used or the technique employed. High order multiple pregnancy and its sequela is a well established complication of controlled ovarian hyperstimulation. This could be a result of multiple ovulations or more than one embryo replacement. Reducing the number of embryos transferred can reduce this more serious adverse effect for expectant mothers and for children conceived from ART.

Gonadotropins↗

Reproductive technologies 1998: options available for the cancer patient.

Recent advances in the field of reproduction have potentially opened opportunities for the preservation of the reproductive potential of young cancer patients with good long-term prognosis for survival. In the postpubertal male, cryopreservation of ejaculated sperm is both feasible and potentially successful. Semen parameters at the time of procurement are of minor significance; intracytoplasmic sperm injection (ICSI) can bypass sperm concentration and motility problems and can lead to successful fertilization. For the prepubertal male there are no clinically applicable options insofar as extraction and cryopreservation of postmeiotic sperm cells (mature spermatozoa or round spermatids) is not feasible. To date, efforts for culture of testicular tissue and in vitro maturation of male germ cells have not been successful. In both pre- and postpubertal females, cryopreservation of ovarian cortical tissue or enzymatically extracted follicles and the in vitro maturation of preantral follicles are of potential clinical use, but, to date, these approaches have been successful only in laboratory animals. An additional option available to the postpubertal female is the stimulation of ovaries with exogenous gonadotropins and retrieval of mature oocytes for cryopreservation. The recent application of ICSI in previously cryopreserved human mature oocytes has improved fertilization rates and has resulted in live births. Unfortunately, a shortcoming of this approach is the limited number of oocytes that can be harvested after stimulation of the ovaries. Further, all these approaches potentially harbor the risk of the cryopreservation of malignant cells with their subsequent reintroduction in the patient at a later date. This is a more realistic concern for patients suffering from hematologic or gonadal tumors. Finally, even though cryopreservation of embryos has been successfully used for many years, this option is not available to the pediatric and adolescent patient. It should not be forgotten that, even if the patients' own gametes are not available in the future, donor sperm and eggs provide the option for offspring and can give the opportunity to the females to carry a pregnancy as long as their uterus has not been affected by the cancer treatment. Given the rapid progress we are witnessing in the field of reproductive medicine, it is probable that in the very near future most of the options described and newer ones will be clinically available.

Adolescent↗

Day 2 vs. day 3 embryo transfer after intracytoplasmic sperm injection. A prospective, randomized study.

OBJECTIVE: To compare, in a prospective, randomized study, implantation and pregnancy rates between day 2 and day 3 embryo transfer intracytoplasmic sperm injection (ICSI). STUDY DESIGN: A total of 106 patients undergoing ICSI cycles who had at least 1 embryo suitable for cryopreservation were prospectively randomized into 2 groups: group I, embryo transfer performed on day 2; group II, embryo transfer performed on day 3. RESULTS: Patient ages did not differ (P = .58) between groups I (33.1 +/- 4.5) and II (32.7 +/- 4.4). The number of oocytes retrieved from group I (13.7 +/- 5.2) was similar (P = .82) to that retrieved from group II (13.7 +/- 5.4). In addition, there was no difference (P = .30) in the number of oocytes retrieved at metaphase II between groups I (10.6 +/- 4.4) and II (9.7 +/- 4.2). Fertilization and cleavage rates were also similar (P = .58 and P = .50, respectively) between groups I (78.2 +/- 14.0% and 98.7 +/- 4.3%) and II (76.2 +/- 14.8% and 99.8 +/- 1.24%, respectively). The total number of embryos and of embryos transferred were similar (P = .22 and P = .36; respectively) for groups I (8.0 +/- 3.0, 2.8 +/- 0.7) and II (7.16 +/- 3.2, 2.6 +/- 0.8). Pregnancy rates per transfer, implantation rates and abortion rates were also similar for groups I (43.4%, 20.8% and 8.7%, respectively) and II (41.5%, 24.1% and 23%, respectively) (P = 1.0, P = .57 and P = .24, respectively). CONCLUSION: The results suggest that extending the embryo culture period from 2 to 3 days for patients who had at least 1 embryo left for cryopreservation had no effect on implantation, pregnancy or abortion rates in an ICSI program.

Adult↗

General anesthesia versus monitored anesthesia care with remifentanil for assisted reproductive technologies: effect on pregnancy rate.

STUDY OBJECTIVES: To compare the outcome of assisted reproductive technology procedures in women who undergo monitored anesthesia care (MAC) with remifentanil versus general anesthesia. DESIGN: Retrospective data analysis. SETTING: University hospital. PATIENTS: 251 ASA physical status I and II women participating in an in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) program. INTERVENTIONS: During the first phase of the study, all patients underwent general anesthesia induction with alfentanil, propofol, and nitrous oxide, which was maintained with isoflurane or propofol infusion. In the second phase of the study, all patients received a standardized MAC technique with a remifentanil infusion; local anesthetics were not used. MEASUREMENTS: The primary endpoint was pregnancy rate per transfer. The number of oocytes collected, fertilized, and cleaved was recorded, as was the number of oocytes transferred. MAIN RESULTS: Patients who underwent MAC had a greater pregnancy rate with IVF (28.2 vs. 16.3%), with ICSI (32.2% vs. 18.8%), and overall (30.6% vs. 17.9%). CONCLUSIONS: Pregnancy rates in women undergoing transvaginal oocyte retrieval for assisted reproductive technologies were significantly higher with a remifentanil-based MAC technique than with a general anesthetic technique.

Adult↗

Contribution of embryo cryopreservation to elective single embryo transfer in IVF-ICSI.

Single embryo transfer is the best way to reduce the risk of multiple pregnancy in IVF-intracytoplasmic sperm injection (ICSI). Between June 2002 and December 2004, all patients (first cycle, female age <38 years) were offered the choice between having one (SET) or two (DET) embryos transferred. Among 493 couples, 428 had at least two good quality embryos, and among them, 32% opted for SET. The SET and DET populations were not comparable (patients in the SET group were younger and had more oocytes retrieved), and therefore a paired, case-control analysis was performed involving 130 SET couples and 130 DET couples, matched according to the female partners' ages and the numbers of embryos available. All of the SET patients, and 82% of the DET group, had at least one embryo cryopreserved, (3.9 versus 2.8 embryos). The option of SET was continued for the frozen-thawed embryo transfers. The pregnancy rate following embryo transfer was significantly lower after SET compared with DET for both fresh (27.6 versus 36.9%; P < 0.05) and frozen-thawed (14.4 versus 23.5%) embryos. However, the cumulative live birth rates following the transfer of fresh and frozen embryos were identical between the two groups (43 versus 45%), with a high prevalence of twins following DET (34 versus 0%).

Adult↗

A double-blind, randomized study to compare recombinant human follicle stimulating hormone (FSH; Gonal-F) with highly purified urinary FSH (Metrodin) HP) in women undergoing assisted reproductive techniques including intracytoplasmic sperm injection. The French Multicentre Trialists.

This prospective, double-blind, randomized, multicentre study compared the efficacy and safety of recombinant human follicle stimulating hormone (r-hFSH; Gonal-F((R))) versus highly purified urinary FSH (u-hFSH HP; Metrodin((R)) HP) in women undergoing ovarian stimulation for in-vitro fertilization, including intracytoplasmic sperm injection. A total of 278 patients began a long gonadotrophin-releasing hormone agonist protocol, then 139 received r-hFSH and 139 u-hFSH HP, 150 IU/day administered s.c., for the first 6 days of treatment. On day 7, the dose was adjusted, if necessary, according to ovarian response. Human chorionic gonadotrophin (HCG, 10 000 IU, s.c.) was administered once there was more than one follicle 18 mm in diameter and two others >/=16 mm. Oocyte retrieval was performed 36-38 h after HCG injection: 128 patients (92%) receiving r-hFSH and 113 (81%) receiving u-hFSH HP had at least one oocyte retrieved. Among patients receiving r-hFSH, there was a significantly higher mean (+/- SD) number of oocytes retrieved (11.0 +/- 5.9 versus 8.8 +/- 4.8 with u-hFSH HP; P = 0. 002) and mean number of embryos obtained (5.1 +/- 3.7 versus 3.5 +/- 2.9 with u-hFSH HP; P = 0.0001). With r-hFSH, significantly fewer FSH treatment days (11.7 +/- 1.9 versus 14.5 +/- 3.3) and 75 IU ampoules (27.6 +/- 10.2 versus 40.7 +/- 13.6) were required than with u-hFSH HP (P = 0.0001). Embryo replacement on day 2-3 after oocyte retrieval resulted in 36 liveborn children in the Gonal-F((R)) group and 33 in the Metrodin HP((R)) group (not significant). There were seven cases (5.0%) of ovarian hyperstimulation syndrome in the r-hFSH group and three (2.2%), in the u-hFSH HP group (not significant). It is concluded that r-hFSH is more effective than u-hFSH in inducing multiple follicular development.

Adolescent↗

Successful pregnancy following transfer of embryos from oocytes with abnormal zona pellucida and cytoplasm morphology.

The failed or impaired fertilization in an IVF cycle may be a result of undetected abnormalities in sperm function, poor oocyte quality, or impaired spermatozoon-oocyte interaction. Whether oocyte dysmorphisms have an impact on intracytoplasmic sperm injection (ICSI) outcome, fertilization, and implantation is controversial. A 33-year-old nulligravida female with a 2-year history of primary infertility was referred to the Toronto Centre for Advanced Reproductive Technology for infertility management. The patient underwent several cycles of ovulation induction followed by timed intercourse or intrauterine insemination without a resulting pregnancy. Following the failed insemination cycles, she proceeded to IVF. Six morphologically abnormal oocytes (including three that were cucumber-shaped) were retrieved and all injected with a single spermatozoon. Four oocytes showed normal fertilization and developed to day-3 embryos with abnormal morphology and were transferred. Two weeks after the embryo transfer, the patient had a positive beta-human chorionic gonadotrophin (beta-HCG). The pregnancy was uneventful, and a healthy baby boy was delivered at 41 weeks of age by Caesarean section. Since fertilization, embryo development, and successful pregnancy was achieved in this case, it is recommend that oocytes with extreme morphological abnormalities should not be discarded as ICSI may overcome the barriers to fertilization and cleavage.

Adult↗

Administration of beta2-adrenergic agonists during the peri-implantation period does not improve implantation or pregnancy rates in intracytoplasmic sperm injection (ICSI) cycles.

PURPOSE: The objective of the present investigation was to determine implantation and pregnancy rates in patients undergoing ICSI and treated with beta2-adrenergic agonists, considering the uterine-relaxing action of these agents. METHODS: A total of 225 women undergoing ICSI at the Center for Human Reproduction, "Sinhá Junqueira" Maternity Foundation, entered the study. Patient participation in each group was random, by drawing lots, using a randomization table previously elaborated for the study (2:2:1). The group I (90 women) received 10 mg of terbutaline daily for 15 days starting on the day of oocyte retrieval; group II (90 women) received 20 mg of ritodrine daily during the same period of time as group I; group III (45 patients) received no treatment and was used as control. The evaluation was interrupted in 3 patients of group I and in 30 patients of group II because of a high incidence of side effects. RESULTS: Pregnancy, implantation, and miscarriage rates were not significantly different (p > 0.05) between the three groups: 29.88%, 13.25%, and 26.9% for group I; 33.33%, 17.5%, and 10.0% for group II; 28.88%, 15.07%, and 15.38% for group III, respectively. CONCLUSIONS: The results of this study do not support the routine use of beta2-adrenergic agonists during the peri-implantation period in assisted reproductive technology cycles.

Adrenergic beta-2 Receptor Agonists↗

Reproductive outcome of polycystic ovarian syndrome patients treated with GnRH antagonists and recombinant FSH 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) and 200 IU in 43 women with 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), respectively. In conclusion, in GnRH antagonist cycles a worse reproductive outcome is expected in PCOS patients with BMI >29 kg/m(2) in whom stimulation is initiated with 200 IU of rFSH as compared with PCOS patients with BMI </=29 kg/m(2) in whom stimulation is initiated with 100 IU of rFSH.

Adult↗

The use of gonadotrophin releasing-hormone analogues (GnRHa), in in-vitro fertilization: some clinical and experimental investigations of a direct effect on the human ovary.

Several lines of investigation suggest a direct modulatory role for gonadotrophin-releasing hormone (GnRH) on granulosa cell functions. Also, GnRH and its analogues (GnRHa) have been implicated in the resumption of meiosis, both in vivo and in vitro. Despite the presence of specific receptors for GnRH on human granulosa and luteal cells, very little is known about the possible effects of this hormone on the ovary. The use of GnRHa for long periods of time in patients undergoing in vitro fertilization (IVF) may influence granulosa cell function and/or oocyte maturation. We describe our clinical and experimental data in which we have searched for evidence of a direct action of GnRHa on the ovary. We have found that the retrieval of higher numbers of oocytes in women treated with GnRHa is correlated with oocytes of lower quality, manifested by a decreased fertilization and implantation rate. This impairment seems to be the consequence of oocyte immaturity, as ascertained by cytogenetic analysis of unfertilized oocytes in which an increase in diploidy, as well as prematurely condensed sperm chromosomes of the G1 phase, was observed in women with an excessive response to the stimulating drugs. Follicular atresia was not increased in women treated with GnRHa. Thus, there was no evidence for a direct effect of GnRHa on the human oocyte. Rather, the observations reflect the harmful effect of pushing follicles in early stages of development using this stimulation protocol. We have also searched for possible effects of GnRHa on granulosa-luteal cells obtained at ovum collection. In vitro culture of these cells has shown that the steroidogenic pathway is affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Count↗

Comparative efficacy and safety of cetrorelix with or without mid-cycle recombinant LH and leuprolide acetate for inhibition of premature LH surges in assisted reproduction.

An open label, randomized, multi-centre study was performed to compare cetrorelix and leuprolide acetate for prevention of premature LH surge and to assess whether patients treated with cetrorelix benefit from addition of recombinant human (r-h)LH. Normo-ovulatory women (n = 74) undergoing ovarian stimulation prior to intracytoplasmic sperm injection were treated with leuprolide acetate (n = 25) before ovarian stimulation with recombinant human FSH (r-hFSH) or with cetrorelix 3 mg on stimulation day 7 (with (n = 25) or without (n = 24) r-hLH 150 IU on days 7-10). The main outcome measures were the number of metaphase II (MII) oocytes retrieved; secondary efficacy end-points; adverse events (AE) and other safety measures. There were no significant differences between groups for MII oocytes retrieved, duration of stimulation, total r-hFSH dose and pregnancy rates. The group treated with cetrorelix alone had a significantly lower concentration of oestradiol per follicle compared with the other groups. The majority of AE were mild to moderate in severity. Cetrorelix and leuprolide acetate appear to have comparable efficacy and safety, although cetrorelix has the advantage of typically requiring only one injection.

Adolescent↗

[A randomized, controlled trial comparing follicle stimulating hormone (FSH) to human menopausal gonadotropin (hMG) in fertilization in vitro].

The adverse effect of raised luteinizing hormone (LH) concentrations on reproductive outcome suggests that exogenous LH administration for ovarian stimulation may not be desirable. The aim of this study was to compare the clinical pregnancy rates between follicle stimulating hormone (FSH) and human menopausal gonadotrophin (HMG) used in in-vitro fertilization (IVF) cycles. A total of 232 infertile patients, with a mean duration of infertility of 67.1 +/- 32.9 months, were selected for IVF (female age < 38 years, FSH < 15 IU/l, and total motile sperm count > 5 x 10(6). A short (flare-up) protocol with daily leuprolide acetate was followed randomly from day 3 with FSH (n = 115) or human menopausal gonadotrophin (HMG; n = 117), at an initial dose of two ampoules per day. A maximum of three embryos was transferred, and the luteal phase was supported with four doses of HCG (2,500 IU). No differences were observed between the two groups in any of the cycle response variables except fertilization rates per oocyte and per patient, both of which were significantly higher with FSH. Clinical pregnancy rates per cycle initiated, per oocyte retrieval and per embryo transfer were 19.1, 21.0 and 22.7% respectively for FSH, and 12.0, 12.8 and 15.4% respectively for HMG. Whilst these differences were not statistically significant, the results of this interim analysis suggest that HMG may be associated with a lower clinical pregnancy rate than FSH.

Adult↗

Randomized controlled trial of follicle stimulating hormone versus human menopausal gonadotrophin in in-vitro fertilization.

The adverse effect of raised luteinizing hormone (LH) concentrations on reproductive outcome suggests that exogenous LH administration for ovarian stimulation may not be desirable. The aim of this study was to compare the clinical pregnancy rates between follicle stimulating hormone (FSH) and human menopausal gonadotrophin (HMG) used in in-vitro fertilization (IVF) cycles. A total of 232 infertile patients, with a mean duration of infertility of 67.1 +/- 32.9 months, were selected for IVF (female age < 38 years, FSH < 15 IU/l, and total motile sperm count > 5 x 10(6)). A short (flare-up) protocol with daily leuprolide acetate was followed randomly from day 3 with FSH (n = 115) or human menopausal gonadotrophin (HMG; n = 117), at an initial dose of two ampoules per day. A maximum of three embryos was transferred, and the luteal phase was supported with four doses of HCG (2500 IU). No differences were observed between the two groups in any of the cycle response variables except fertilization rates per oocyte and per patient, both of which were significantly higher with FSH. Clinical pregnancy rates per cycle initiated, per oocyte retrieval and per embryo transfer were 19.1, 21.0 and 22.7% respectively for FSH, and 12.0, 12.8 and 15.4% respectively for HMG. Whilst these differences were not statistically significant, the results of this interim analysis suggest that HMG may be associated with a lower clinical pregnancy rate than FSH.

Androgens↗

Effect of reduced oocyte aging on the outcome of rescue intracytoplasmic sperm injection.

OBJECTIVE: To evaluate the results of a novel protocol that allows to rescue IVF unfertilized oocytes by intracytoplasmic sperm injection (ICSI). DESIGN: Prospective clinical trial. SETTING: Private reproductive medical center. PATIENT(S): Thirty patients undergoing IVF. INTERVENTION(S): Controlled ovarian stimulation (COS), conventional IVF, rescue ICSI, embryo culture, and embryo transfer. MAIN OUTCOME MEASURE(S): Identification of unfertilized IVF oocytes 6 hours after insemination and fertilization, and developmental rates of those oocytes after rescue microinjection, as well implantation and pregnancy rates (PR). RESULT(S): All oocytes (392) from 30 patients were inseminated with standard IVF 3 hours after ovum pick-up. Polar body (PB) status was checked at decumulation and rechecked 3 hours later. Eighty-two oocytes were fertilized after IVF alone and 184 nonactivated oocytes (failed fertilization) were rescue microinjected and 166 of them fertilized (20 patients). Cleavage stage on day 2 was significantly more advanced and embryo grade was higher after standard IVF fertilization than after rescue ICSI. Eight of the 30 embryos transferred were implanted in the IVF-only patients (27%) and 8 of 68 embryos in the rescue ICSI patients (12%). CONCLUSION(S): Rescue ICSI of unfertilized IVF oocytes 6 hours after insemination (9 hours after egg retrieval) can provide normal fertilization, embryo development, and pregnancy; however, corresponding outcome parameters tend to be impaired in comparison to the standard IVF fertilization results.

Adult↗