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PubMed2000

Distinction between early and late ovarian hyperstimulation syndrome.

OBJECTIVE: To compare patient and cycle characteristics among three study groups: early ovarian hyperstimulation syndrome (OHSS), late OHSS, and non-OHSS. DESIGN: Prospective observational study. SETTING: University assisted conception service. PATIENT(S): Women undergoing in vitro fertilization, intracytoplasmic sperm injection or gamete intrafallopian transfer treatment at Bristol University In Vitro Fertilization Service between January 1, 1995, and December 31, 1998. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Patient age, prevalence of polycystic ovaries, gonadotropin requirement, peak serum estradiol (E(2)) concentration, number of oocytes retrieved, clinical pregnancy rate, number of gestation sacs, and severity of OHSS. RESULT(S): Women with early OHSS had significantly higher serum E(2) levels and lower gonadotropin requirements than did the other groups. Cycles with either early or late OHSS had significantly more oocytes collected than those without OHSS. Serum E(2) and oocyte numbers did not accurately predict the risk of developing late OHSS. Clinical pregnancies occurred in all cycles with late OHSS, and multiple pregnancies were significantly more frequent in the late OHSS group than in the other groups. Late OHSS was more likely than early OHSS to be severe. CONCLUSION(S): Early OHSS relates to "excessive" preovulatory response to stimulation, whereas late OHSS depends on the occurrence of pregnancy, is likelier to be severe, and is only poorly related to preovulatory events.

Adult↗
PubMed1999

Recurrent empty follicle syndrome successfully treated with recombinant human chorionic gonadotrophin.

We report a case of a patient with polycystic ovary syndrome and primary infertility who was admitted to our in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) programme because of her partner's severe oligozoospermia and asthenozoospermia. Ovarian stimulation was accomplished in the three treatment cycles using gonadotrophin therapy after a dual approach with ovarian suppression using oral contraceptive pills followed by gonadotrophin-releasing hormone agonist therapy. Oocyte retrieval was unsuccessful in the first two treated cycles despite the fact that human chorionic gonadotrophin (HCG) from three different batches was used. In the third treatment cycle, recombinant HCG was used and five oocytes were retrieved. This is the first report of recurrent empty follicle syndrome despite the use of different batches of commercially available urinary HCG, and of its successful treatment using recombinant HCG.

Adult↗
PubMed2006

Successful delivery after the transfer of twice-vitrified embryos derived from in vitro matured oocytes: a case report.

We report here the first case of successful pregnancy and delivery after the blastocyst transfer of twice-vitrified embryos produced following in vitro maturation (IVM) and ICSI. The patient received 5000 IU hCG on day 12 of the treatment cycle, and oocyte retrieval was carried out 36 h after hCG injection. A total of 22 immature oocytes were obtained. Following incubation for 26 h in IVM medium, 15 oocytes (68.2%) reached metaphase II stage. In total, 13 oocytes (86.7%) were fertilized after ICSI with the husband's sperm, and 11 embryos at the pronuclear stage and two cleaved embryos on day 2 were vitrified because of thin endometrial thickness. Eight cryopreserved embryos at the pronuclear stage were warmed and cultured until the day 3 stage. Three embryos were transferred, and three embryos were twice vitrified. Unfortunately, these transferred embryos did not implant. Three twice-vitrified embryos were rewarmed and cultured until the day 5 stage, and two embryos were transferred. The second transfer attempt of twice-vitrified embryos resulted in the full-term delivery of a healthy infant. This case report demonstrates that twice-vitrified embryos, developed using an IVM protocol, retain the developmental competence for full-term, healthy infants.

Adult↗
PubMed2005

The role of ketoconazole in the prevention of ovarian hyperstimulation syndrome in patients with polycystic ovary syndrome during assisted reproductive technology cycles.

OBJECTIVE: To assess the clinical efficacy of ketoconazole (KCZ) as an inhibitory enzyme on ovarian steroidogenesis, in prevention of ovarian hyper- stimulation syndrome (OHSS) during assisted reproductive technology (ART) in patients with polycystic ovarian syndrome (PCOS). METHODS: We included 58 PCOS patients, enrolled for in-vitro fertilization or intracytoplasmic sperm injection in a randomized clinical trial between November 2000 and October 2001 in the Royan Institute, Tehran, Iran. Twenty-eight patients received KCZ during the stimulation phase and 30 patients were controls. We compared serum E2 levels, number of lead follicles, number of retrieved oocytes, fertilization rate, occurrence of OHSS and cancellation rate using student's t-test, Chi-square and Fisher exact test. RESULTS: We found no significant differences between the 2 groups in the peak serum estradiol level, the number of lead follicles, oocytes, and fertilization rate. One patient in the control group had clinical symptoms of severe ovarian hyperstimulation, and none from the treated group. CONCLUSION: This study reveals no significant effect of KCZ on the incidence of OHSS during ART cycles; however, also no significant negative effects of KCZ on the number and maturity of oocytes or on fertilization rate.

Adult↗
PubMed2000

Analysis of the bleeding pattern in assisted reproduction cycles with luteal phase supplementation using vaginal micronized progesterone.

This study was designed to determine the effects of a vaginal micronized progesterone preparation on bleeding patterns and pregnancy outcomes after in-vitro fertilization and intracytoplasmic sperm injection (IVF-ICSI). The study population consisted of 149 consecutive women who had undergone IVF-ICSI using 'long-protocol' stimulation with buserelin-human menopausal gonadotrophin (HMG). A retrospective chart analysis of computerized medical records was undertaken. Vaginal progesterone (200 mg three times daily) was begun the day before oocyte retrieval and continued for a minimum of 16-19 days following human chorionic gonadotrophin (HCG) administration. Occurrence of bleeding following HCG injection, pregnancy rate and outcomes, and serum concentrations of oestradiol were measured. Women undergoing IVF and embryo transfer with ICSI and using vaginal progesterone for luteal support had normal luteal phase lengths (day of HCG minus day of onset of bleeding). In the absence of pregnancy, bleeding occurred after 19.2 +/- 3.9 days (mean +/- SD). Out of the pregnant group only three women bled within 19 days of HCG administration: two had biochemical pregnancies which spontaneously vanished and one evolved to term. The results reflect the normal bleeding pattern to be expected when vaginal progesterone is used for luteal support in IVF and embryo transfer, an approach whose efficacy has been amply proven. No shortened luteal phases were observed using vaginally administered progesterone.

Adult↗
PubMed1998

Continuing the debate on empty follicle syndrome: can it be associated with normal bioavailability of beta-human chorionic gonadotrophin on the day of oocyte recovery?

This paper describes our experience with four ovarian stimulation in-vitro fertilization (IVF) cycles in which we failed to retrieve oocytes despite normal bioavailability of beta-human chorionic gonadotrophin (beta-HCG) in patients' blood 35 h after HCG administration. In three cases, the oocyte recovery procedure was interrupted, a second dose of HCG was administered and 24 h later mature oocytes were collected from two of the patients. In the first case, the three metaphase II oocytes collected fertilized after intracytoplasmic sperm injection (ICSI) and two cleaved grade three embryos were transferred but pregnancy did not ensue. In the second case, six out of eight metaphase II oocytes fertilized and cleaved following ICSI, leading to transfer of one grade two and two grade three embryos. This resulted in a clinical pregnancy which at the time of this report is ongoing. A similar rescue protocol was used for the third case who had empty follicle syndrome (EFS) in her previous treatment cycle but only cumulus-corona complexes were aspirated. Five additional patients who had EFS before instituting pregnancy diagnostic test screening have had further treatment cycles in which oocytes were collected but pregnancy did not ensue. We conclude that normal bioavailability of beta-HCG on the day of oocyte recovery does not exclude the diagnosis of EFS. EFS does not predict a reduced fertility potential in future cycles, although it may recur due to a biological abnormality in the availability of mature oocytes that are retrievable. In such patients, oocyte donation may offer the chance of achieving a pregnancy.

Adult↗
PubMed2001

A prospective randomized comparison of routine buserelin acetate and a decreasing dosage of nafarelin acetate with a low-dose gonadotropin-releasing hormone agonist protocol for in vitro fertilization and intracytoplasmic sperm injection.

OBJECTIVE: To compare the efficacy of a draw-back nafarelin acetate protocol with routine buserelin acetate administration for in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). DESIGN: Prospective clinical study. SETTING: Mie University School of Medicine, Tsu, Mie, Japan. PATIENT(S): One hundred sixty-nine women treated with IVF and 183 women treated with ICSI. INTERVENTION(S): Nafarelin acetate and buserelin acetate in ovarian hyperstimulation in IVF and ICSI were administered. MAIN OUTCOME MEASURE(S): The concentrations of estradiol (E(2)), FSH, LH, gonadotropin dosages; the number of oocytes retrieved, oocytes fertilized, and embryos; and pregnancy rates. RESULT(S): A prospective study was conducted with 44 cycles for 34 couples with nafarelin acetate (group 1) and 47 cycles for 40 couples with buserelin acetate (group 2) with a long IVF protocol; 68 cycles for 46 couples with nafarelin acetate (group 3) and 56 cycles for 39 couples with buserelin acetate (group 4) with a short IVF protocol; 39 cycles for 32 couples with nafarelin acetate (group 5) and 50 cycles for 30 couples with buserelin acetate (group 6) with a long ICSI protocol; and 87 cycles for 60 couples with nafarelin acetate (group 7) and 81 cycles for 61 couples with buserelin acetate (group 8) with a short ICSI protocol. Patients were randomized to receive either full-dose nafarelin acetate (200 microg b.i.d.) treatment for 7 days followed by half-dose nafarelin acetate (200 microg daily) or buserelin acetate (300 microg t.i.d.). There were no statistically significant differences in baseline concentrations of E(2) and FSH, concentrations of E(2), P4, FSH, LH on hCG administration, gonadotropin dosage, the number of oocytes retrieved and embryos transferred, or pregnancy rates between groups 1 and 2, groups 3 and 4, groups 5 and 6, and groups 7 and 8. CONCLUSION(S): Full-dose nafarelin acetate treatment for 7 days followed by half-dose nafarelin acetate ("draw-back" protocol) is an effective new protocol for IVF and ICSI.

Abortion, Spontaneous↗
PubMed2000

Conservative management versus aspiration of functional ovarian cysts before ovarian stimulation for assisted reproduction.

PURPOSE: To compare the efficiency of transvaginal ultrasound-guided functional ovarian cyst aspiration, with conservative management, in the outcome of patients undergoing assisted reproductive technique (ART) (in vitro fertilization or intracytoplasmic sperm injection). These cysts were identified before ovarian stimulation begun and after administration of a midluteal GnRH agonist. METHODS: Fifty nine patients undergoing ART from January 1, 1997 to February 28, 1999, who developed functional ovarian cysts were included. Aspirations of these cysts (n = 14) versus conservative management (observation) (n = 45) were compared. Total number of ovarian follicles developed, number of oocytes retrieved, estradiol levels on the day of human chorionic gonadotropin, fertilization rate, number of good quality embryos transferred, implantation, and clinical pregnancy rate per cycle were evaluated. RESULTS: No statistical differences were observed between the two groups in any of the selected parameters. CONCLUSIONS: Cyst aspiration and conservative management showed similar implantation and pregnancy rates, in patients who develop functional ovarian cysts after pituitary down-regulation following luteal phase gonadotropin-releasing hormone agonist administration. Prospective studies are needed to confirm this trend.

Adult↗
PubMed1990

Fertilization failure in IVF: why and what next?

Among 297 couples who underwent 587 oocyte collection procedures, 95 (16%) total fertilization failures (FF) were observed. This frequency is similar in couples with either normal or only mildly deficient spermatozoa (16.2 and 13.7% respectively) but is almost doubled in cases of moderately and severely defective sperm (26.5%). However, this latter group accounts for only 19% of FF events. The fertilization rate per oocyte (FR) follows an inverse trend. FR was correlated with the final (i.e. after swim-up) sperm count and with initial and final motility of the sperm sample. If the final count and motility were less than 2 x 10(6)/ml and 40% respectively, the FF frequency in the group with partner's spermatozoa was significantly higher and FR significantly lower. FR was inversely correlated with the number of oocytes recovered but FF was found significantly more frequently only when fewer than three eggs were retrieved. No correlation was found between FF and either female causes of infertility, age or dosage of stimulation treatment. However, in the group with donor spermatozoa the FR was significantly lower amongst tubal, endocrinopathic and endometriotic patients (67.6, 67.2 and 56.6 respectively versus 79.7% in harvests from idiopathic cases). FR was decreased and FF increased when ovulation induction resulted from a spontaneous LH peak supplemented with human chorionic gonadotropin (HCG), as compared to induction by HCG alone. In the group using normal or mildly defective spermatozoa, if FF occurs at the first attempt, the frequency of recurrence in further trials is high (29%) and the probability of pregnancy after completed trials is low (12.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1989

Evaluation of a synthetic serum substitute to replace fetal cord serum for human oocyte fertilization and embryo growth in vitro.

A comparison was made between a serum substitute. UltroSer G (Gibco, Ghent, Belgium) (2%) (medium B) and 10% human fetal cord serum (medium A), as regards their ability to support 1-cell and 2-cell mice embryo development in vitro. Sixty percent and 56% of the 1-cell embryos reached the expanded blastocyst stage when cultured in media A and B, respectively. Eighty-four percent and 88% of 2-cell embryos reached the expanded blastocyst stage when cultured in media A and B, respectively. A prospective randomized study was then performed to evaluate this synthetic serum substitute in human in vitro fertilization. Among 141 ovum pick-up (OPU), oocytes retrieved in 74 cases were processed in medium A and oocytes retrieved in 67 others in medium B. In media A and B, the fertilization rate was 67% and 44.3% respectively, and the pregnancy rate/OPU 23% and 9%, respectively. The pregnancy rate/transfer was 28.8% and 12.2% respectively, and the implantation rate/transferred embryo 9.5% and 4.2%. In the human sperm survival assay, the vitality and residual motility after 24 hours of incubation were significantly lower in medium B. In conclusion, UltroSer G successfully sustained the development in vitro of mouse embyros. However in human, it reduced sperm survival, oocyte fertilization, and embryo viability.

Animals↗
PubMed1996

Is intracytoplasmic sperm injection (ICSI) a safe procedure? What do we learn from early pregnancy data about ICSI?

The aim of this study was to evaluate the safety of the intracytoplasmic sperm injection (ICSI) procedure by analysing early pregnancy data from ICSI and in-vitro fertilization (IVF) patients. In all, 50 ICSI pregnancies were compared with 226 IVF pregnancies. Comparisons were made during the first 9 weeks after the theoretical last menstrual period (7 weeks after oocyte retrieval) with regard to epidemiological data, plasma hormonal concentrations and transvaginal ultrasonographical findings. Although patients were significantly (P < 0.001) younger in ICSI (31 years) than in IVF pregnancies (33 years), their duration of infertility was similar. Miscarriage and multiple gestation rates were not significantly different in ICSI pregnancies (respectively 24 and 24%) from those found after IVF (32 and 29%). The probability of developmental arrest of the intrauterine sac (miscarriages and vanishing twins) was similar in both ICSI (16%) and IVF (25%) cases. The mean plasma hormonal concentrations starting from day 11 after oocyte retrieval were similar in both groups. Every ICSI and IVF pregnancy showed an embryo with cardiac activity at 7 weeks. Early pregnancy data did not show any abnormal findings for pregnancies achieved using ICSI compared to those achieved by IVF.

Abortion, Therapeutic↗
PubMed1995

Intracytoplasmic sperm injection of mouse oocytes with 5 mM Ca2+ at different intervals.

The objective of this investigation was to determine whether intracytoplasmic sperm injection (ICSI) can be performed in the mouse. Metaphase II oocytes were obtained from F1 hybrid mice (C57BL x CBA) by i.p. injections of 10 IU pregnant mare's serum gonadotrophin (PMSG) and human chorionic gonadotrophin (HCG) administered 48 h apart. Oocytes with cumulus oophorus were retrieved 13-14 h post HCG. Cumulus was dispersed with 0.1% hyaluronidase. Mouse spermatozoa were obtained from the cauda epididymides of males of the same strain. The spermatozoa were processed by the standard swim-up procedure. The harvested spermatozoa were then incubated for 1.5 h to allow capacitation. Healthy oocytes were injected with 3-4 pl 5 mM Ca2+, followed by one live morphologically normal spermatozoon into the cytoplasm at intervals of 0, 0.5, 1, 2 and 3 h. The proportion of 2-cell embryos that developed from oocytes injected with Ca2+ and spermatozoa ranged between 29.5 and 36.5% in all groups, with no statistical difference between treatments. Chromosomal analysis showed that two-thirds of the ICSI-derived 2-cell embryos were diploid. The proportion of parthenogenetically activated embryos in the ICSI groups was similar to that in the control group (8-10%) which was injected with Ca2+ and polyvinyl pyrrolidone only. The proportion of blastocysts that developed in culture from the ICSI-derived 2-cell embryos was of the order of 36-42%. Some blastocysts were used for cell number counts. There was a significant increase in total and inner cell mass counts of blastocysts in which the spermatozoon was injected at 2 and 3 h following Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Oocyte quality in patients with severe ovarian hyperstimulation syndrome: a self-controlled clinical study.

OBJECTIVE: To investigate the oocyte quality in patients with severe ovarian hyperstimulation syndrome (OHSS). DESIGN: Self-controlled clinical study. SETTING: University teaching hospital. PATIENT(S): Twenty-two patients from our assisted reproductive technology (ART) program who developed severe OHSS during their first controlled ovarian hyperstimulation for IVF or intracytoplasmic sperm injection (ICSI) (OHSS cycles) during a period of 10 years and had a second ART attempt performed in our center in which OHSS did not develop (control cycles). INTERVENTION(S): IVF and ICSI. MAIN OUTCOME MEASURE(S): Oocyte yield and quality, fertilization rate, embryo yield and quality, implantation rate, and pregnancy rate. RESULT(S): The total number of oocytes retrieved and the mean number of metaphase II oocytes were significantly higher in patients with OHSS than in control cycles. Fertilization rates were similar in both groups of ART cycles, and thus the number of viable embryos were significantly higher in OHSS cycles. Implantation and pregnancy rates were similar in OHSS and control cycles. Oocyte and embryo yield and quality were similar in early and late OHSS. Oocyte yield and quality, embryological outcome, and implantation and pregnancy rates were similar in patients with and without polycystic ovarian syndrome (PCOS) both in cycles developing OHSS and control cycles. CONCLUSION(S): Oocyte quality is not compromised in severe OHSS cycles irrespective of whether patients had or did not have PCOS.

Adult↗
PubMed1999

[Fertilization of cryopreserved and thawed human oocytes (Cryo-Oo) by injection of spermatozoa (ICSI)--medical management of sterility and case report of a twin pregnancy].

It is reported on a twin pregnancy and parturition of a healthy girl and a healthy boy following the treatment of the mother by intracytoplasmic injection of spermatozoa (ICSI) into cryopreserved and thawed human oocytes (Cryo-Oo). The couple suffered from a primary sterility because of a severe subfertility of the husband and oligomenorrhea with anovulation of the wife. Before the couple contacted our center for the first time, several pretreatments had been carried out, e.g. intrauterine inseminations (IUI) with husband's and donor sperm and one cycle of in vitro fertilization (IVF) with intracytoplasmic sperm injection. This IVF/ICSI-cycle resulted in a tubal pregnancy. It must be noted that the patient showed in each treatment cycle a remarkable tendency to develop ovarian hyperstimulation syndromes (OHSS), even under stimulation with 50 mg clomiphen citrate. In 1997 we started the first treatment cycle for IVF/ICSI with GnIZH-analogues and FSH according to the long protocol. In spite of a low dosage of gonadotropins the patient again developed a impressive multifollicular growth that we decided, together with the couple, only to perform the oocyte retrieval and cryopreserve the collected eggs. For ethic considerations the couple did not consent in the freezing of pronuclear stages. Two months later we performed the transfer-cycle: after thawing of four oocytes, the intracytoplasmic injection of native spermatozoa led to the fertilization of three oocytes and a total of three preimplantation embryos was transferred one day later. Two weeks later the blood level of hCG was 518 IU/ml and an intact twin pregnancy developed. In July 1998, after 36 weeks of gestation, a healthy girl (2540 g) and an healthy boy (2375 g) were delivered by cesarean section. This case report and the experience with further 23 patients (6 pregnancies) demonstrate that ICSI with cryopreserved and thawed oocytes is an effective approach to avoid repetitive oocyte retrievals. The achievable pregnancy rates so far seem to be similar to frozen pronuclear stages, possibly even better. Under the specific regulations of the German Embryo Protection Act (ESchG)--i.e. freezing of embryos not allowed--this technique is worth being pursued with attention.

Adult↗
PubMed1998

Effect of parental age on fertilization and pregnancy characteristics in couples treated by intracytoplasmic sperm injection.

The purpose of this study was to investigate any influence of maternal and/or paternal age on gamete characteristics and pregnancy outcomes in intracytoplasmic sperm injection (ICSI) cycles. In all, 821 consecutive ICSI cases were analysed retrospectively. While a significant linear decline in semen volume was detected, no significant differences in the concentration, motility or morphology of the spermatozoa were found with paternal ageing. A significant decline in the number of oocytes retrieved and the number of mature oocytes obtained was found with advancing maternal age. An increase in the occurrence of digyny was noted with parental ageing, while no difference in single or bipronuclear fertilization was found. Older women had a decreased incidence of single pronucleus formation and an increase in digyny, but no significant difference in the percentage of oocytes that underwent two-pronuclear fertilization was detected with regard to maternal ageing. Pregnancy outcomes were not influenced by the age of the male partner, while a strong negative correlation was found with maternal ageing. To better analyse male partner ageing as a factor affecting pregnancy outcome, we analysed a subgroup of patients with a female partner aged <35 years who underwent ICSI. No paternal influence on ICSI pregnancy outcome was found in this subgroup of patients. We conclude that the influence on pregnancy outcome after ICSI is related mostly to maternal and not paternal age.

Adult↗
PubMed1998

Does withholding gonadotrophin administration prevent severe ovarian hyperstimulation syndrome?

Withholding gonadotrophin administration (coasting) may prevent severe ovarian hyperstimulation syndrome (OHSS). To ascertain the effectiveness of this protection a cohort of 252 consecutive in-vitro fertilization (IVF) or IVF with intracytoplasmic sperm injection (ICSI) cycles was studied. Twenty women with exaggerated response were treated with coasting. Despite coasting, four patients developed severe OHSS requiring hospitalization. Two of these four patients also required paracentesis. Multiple regression analysis in coasting cycles revealed severe OHSS was related to youth, number of oocytes retrieved and serum oestradiol prior to human chorionic gonadotrophin (HCG). Risk of developing severe OHSS was multifactorial and not necessarily prevented by withholding gonadotrophin.

Adult↗
PubMed1996

Testicular sperm recovery in nine 47,XXY Klinefelter patients.

Klinefelter's syndrome is generally characterized by hypergonadotrophic hypogonadism and azoospermia. The clinical features, however, are variable, and occasionally severe oligozoospermia may be present. Usually in these cases a 46,XY/47,XXY mosaic karyotype is involved. However, focal spermatogenesis and severe oligozoospermia have been reported in 47,XXY individuals too. In the present study we investigated whether testicular spermatozoa can be recovered in 47,XXY patients with a view to intracytoplasmic sperm injection (ICSI). In four out of nine apparently non-mosaic 47,XXY patients, spermatozoa were recovered from the wet preparations of testicular tissue and ICSI was performed in three couples. In one patient in whom spermatozoa were successfully recovered and used for ICSI, no spermatozoa were retrieved at a second trial. Although these results show that in some 47,XXY individuals testicular spermatozoa can be successfully recovered and even used for ICSI, at present this approach should be considered experimental. There may indeed be some concern about the chromosomal normality of the embryos generated through this infertility treatment. Patients with Klinefelter's syndrome should therefore be counselled about the complexity of this treatment, which involves multiple testicular biopsies from hypogonadal testes, ICSI and preimplantation diagnosis by fluorescence-in-situ hybridization.

Adult↗