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Short versus long gonadotropin-releasing hormone analogue suppression protocols for superovulation in patients > or = 40 years old undergoing intracytoplasmic sperm injection.

OBJECTIVE: To determine whether the short or long protocol for controlled ovarian hyperstimulation works better in older patients undergoing IVF. DESIGN: Controlled, randomized study. SETTING: A single private IVF center. PATIENT(S): Two hundred twenty infertile women aged > or = 40 years undergoing IVF. INTERVENTION(S): At their first IVF cycle, the women were randomized into two study groups according to a computer-generated number sequence: 110 patients were treated with a long protocol, and the other 110 were treated with a short protocol for controlled ovarian hyperstimulation. MAIN OUTCOME MEASURE(S): Days of stimulation, E2 level at the day of hCG administration, amount of FSH administered, number of oocytes collected, number of embryos obtained, pregnancy rate, implantation rate. RESULT(S): Patients treated with a long protocol showed a significantly higher number of oocytes retrieved, a higher number of embryos obtained, and a higher pregnancy rate, both for cycle and transfer, compared with the short-protocol patients. The other parameters evaluated did not show any statistically significant differences. CONCLUSION(S): Our study showed that the long protocol performed better than the short protocol in older women. Our findings demonstrated that flare-up in older women might be detrimental.

Adult↗

Early cleavage of human embryos to the two-cell stage. A simple, effective indicator of implantation and pregnancy in intracytoplasmic sperm injection.

OBJECTIVE: To evaluate the relationship between embryo cleavage time and implantation and pregnancy rates in women undergoing intracytoplasmic sperm injection (ICSI) for male factor infertility. STUDY DESIGN: A total of 78 patients undergoing their first ICSI cycle were evaluated prospectively. Embryos were assessed for early cleavage to the two-cell stage 27 hours after injection. RESULTS: Early cleavage of at least one embryo was observed in 48 cycles (group I). None of the embryos cleaved early in the remaining 30 cycles (group II). There was no difference regarding mean patient age, duration of ovarian stimulation, number of gonadotropin ampules used, number of oocytes retrieved, fertilization, cleavage rates and embryo quality between the two groups. Implantation and clinical pregnancy rates were significantly higher in group I than II (17.9% and 45.8% vs. 5.1% and 16.7%, respectively; P < .05). Furthermore, progression to the blastocyst stage in excess embryos was significantly higher in group I than II (56.7% vs. 25.0%, P < .05). CONCLUSION: Pregnancy and implantation rates were higher in patients who have early cleaving embryos; absence of early cleavage was associated with a poor outcome.

Adult↗

Distress level in men undergoing intracytoplasmic sperm injection versus in-vitro fertilization.

The purpose of this study was to compare the psychological reactions of men undergoing intracytoplasmic sperm injection (ICSI) (n=18) or in-vitro fertilization (IVF) (n=22). Men monitored their psychological reactions daily for one complete treatment cycle from the first day of down-regulation until the outcome of treatment was known (approximately 52 days). The results showed that ICSI patients reported marginally more distress on the days prior to retrieval than the IVF patients. Other than this difference the pattern of results indicated that the psychological reactions of men undergoing ICSI or IVF were similar and that there was no need to manage these patients differently during treatment. However, ICSI patients may benefit from some reassuring comments on the days prior to retrieval when they showed more anticipatory anxiety.

Adult↗

Transvaginal intratubal embryo transfer: a new treatment of male infertility.

Intratubal embryo transfer is a new method in the treatment of human infertility. Following transvaginal sonographic oocyte retrieval, in-vitro fertilization (IVF) is performed and embryos are transferred into the Fallopian tube transvaginally. In comparison with gamete intra-Fallopian transfer (GIFT), fertilization under in vitro conditions offers the advantage that the success of the fertilization process can be examined. Therefore, this method can give important diagnostic information, especially in cases of poor sperm quality or unexplained infertility. After fertilization in vitro and transfer into the tube, embryonic development occurs in the physiological milieu of the oviduct. Transvaginal intratubal embryo transfer was performed in 95 patients with male factor infertility. In 29 cases (31%), a pregnancy was achieved. One abortion, but no ectopic pregnancy was observed. This method combines the advantages of IVF and GIFT and offers a successful procedure for the treatment of infertility.

Embryo Transfer↗

Treatment of patients with retrograde ejaculation in the era of modern assisted reproduction technology.

PURPOSE: We determined a rational strategy for treatment of patients with retrograde ejaculation in the era of modern assisted reproduction technology. MATERIALS AND METHODS: In 7 consecutive patients medical treatment or retrieval of spermatozoa from the bladder was performed at a male infertility clinic. RESULTS: Antegrade ejaculation was restored in 3 patients, and spermatozoa were retrieved from the bladder and used for assisted reproduction in 3. Spermatozoa with good oolemma penetrating ability were collected by seminal vesicle massage. CONCLUSIONS: Modern assisted reproduction technology is a powerful treatment option for retrograde ejaculation when combined with a technique to retrieve spermatozoa of good quality from the bladder.

Adult↗

The presence and extent of endometriosis do not effect clinical pregnancy and implantation rates in patients undergoing intracytoplasmic sperm injection.

OBJECTIVE: To assess the impact of endometriosis on the outcome of intracytoplasmic sperm injection (ICSI) outcome. STUDY DESIGN: Retrospective case-control study which enrolled 1280 consecutive cycles of 834 couples of ICSI with ejaculated sperm. Among them, 973 cycles of 632 couples had resulted in embryo transfer (ET). The presence of endometriosis was noted in 110 consecutive cycles of 45 patients among which 78 cycles of 44 patients had resulted in ET. Data from endometriosis group were analyzed in subgroups of minimal-mild (49 ET cycles of 25 patients) and moderate-severe (29 ET cycles of 19 patients). The controls consisted of 1170 consecutive cycles of age-matched 771 couples. Of the controls, 588 couples had 895 cycles of ET. Main outcome measures were implantation and clinical pregnancy rates. RESULTS: There were no differences in cycle and ET cancellation rates between control and endometriosis groups. The number of oocytes retrieved, fertilization and cleavage rates and the number and quality of embryos developed and transferred were similar among the groups. The implantation and clinical pregnancy rates were also comparable. CONCLUSION: The presence and extent of endometriosis do not affect implantation and clinical pregnancy rates in patients undergoing ICSI.

Adult↗

[Prognostic values of oestradiol/oocyte rate in ICSI patients].

OBJECTIVES: To analyze the pregnancy rate in women who underwent Intracytoplasmic Sperm Injection (ICSI) program depending of the oestradiol/oocyte index. STUDY DESIGN: Retrospective, comparative. MATERIAL AND METHODS: 332 patients were included. There were divided in three groups depending on the oestradiol/oocyte index: Group A:(100 pg/mL, group B: 101-250 pg/mL and group C: > 250 pg/mL). Therapeutic protocol. Down regulation with leuprolide acetate in late luteal phase protocol, COH with rec-FSH and / or HMG, ultrasonographic and estradiol blood levels were monitored; hCG application when > 3 follicles > 18 mm, oocyte retrieval performed 34 hours later. We analyzed: patient age, male age, number of follicles, estradiol serum levels at the day of hCG application, number of mature oocytes, oestradiol/oocyte index, fertilization rate, transferred embryos, transfer quality, catheter type and luteal support. Statistical analysis (SPSS 11) with chi square, ANOVA and Kruskall-Wallis was used. RESULTS: On having analyzed the number of metaphase II oocytes retrieval, oocytes fertilized and number of transferred embryos among three groups, the best results were obtained in group B. The differences among these variables were significant. (P = 0.014, p = 0.005 and p = 0.003, respectively). When the oestradiol/oocyte index was analyzed and the PR among groups (21.83, 36.62 and 17.80 %) we observed a significant difference (p = 0.003). CONCLUSION: It is convenient to monitor the oestradiol blood levels to offer schemes of COH less aggressive to improve the oocyte quality. The oestradiol/oocyte index is a parameter adapted as a predictive value of pregnancy.

Adult↗

Aspiration of ovarian endometriomas before intracytoplasmic sperm injection.

OBJECTIVE: To investigate whether aspiration of ovarian endometriomas before controlled ovarian stimulation (COH) improves intracytoplasmic sperm injection (ICSI) outcomes. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): A prospective analysis of 171 patients with ovarian endometriosis and tubal factor infertility were divided into four groups: aspiration of endometriomas at the beginning of COH in patients with ovarian endometriomas and no history of previous surgery (n = 41) (group 1); nonaspirated endometriomas (n = 40) (group 2); history of ovarian surgery for endometriomas in patients without ovarian endometriomas at the beginning of COH (n = 44) (group 3); and tubal factor infertility (n = 46) (control group 4). INTERVENTION(S): Aspiration of endometriomas. MAIN OUTCOME MEASURE(S): Clinical parameters, characteristics of COH, and ICSI results were analyzed. RESULT(S): We observed higher levels of E(2) on the day of hCG injection after aspiration of endometriomas compared with nonaspirated endometriomas. When we compared all endometriomas and tubal factor (control) groups, we observed a lower number of total follicles (>17 mm) and metaphase II (MII) oocytes in nonaspirated and resected endometrioma groups and a longer duration of COH in the nonaspirated endometrioma group compared with the tubal factor group. Implantation and clinical pregnancy rates were similar among all groups. CONCLUSION(S): In the current study, all patients with endometriomas had significantly lower numbers of MII oocytes compared with those in patients with tubal factor infertility. We propose that aspiration of endometriomas before COH neither reduces the amount of gonadotropins nor increases the number of follicles >17 mm, the number of MII oocytes retrieved, the implantation rates, or the clinical pregnancy rates. Resection of small endometriomas (1-6 cm) may not present any additional benefits to the IVF-ICSI cycle outcomes.

Endometrial Neoplasms↗

Local experience with zona drilling, zona cutting and sperm microinjection.

Clinical trials were performed between 1987 and 1992 on the use of zona drilling (ZD), zona cutting (ZC) and subzonal sperm microinjection (SZI) for the treatment of severe male infertility. ZD significantly improved the fertilization rate, but embryo morphology was poor and no pregnancies were achieved, so it was abandoned in favour of ZC. The fertilization rate was acceptable in the first trial of ZC but embryo morphology was still poor and no pregnancies were achieved, so a number of protocol changes were instigated. Shrinkage of oocytes in hypertonic sucrose prior to ZC markedly improved embryo quality, whereas transfer of embryos on Day 3 after oocyte retrieval enhanced the pregnancy rate. However, despite these improvements, the overall pregnancy rate in the third ZC trial was still low (16.6% per transfer), so a trial of SZI was initiated in 1992. The overall fertilization rate in 82 SZI cycles was 34.4% and, although the polyspermy rate was high, a clinical pregnancy rate of 30.8% per transfer and an implantation rate of 18.4% per embryo were achieved. These trials demonstrate that SZI is a successful treatment for severe male infertility; under the trial conditions, at least, it was superior to ZD or ZC.

Embryonic and Fetal Development↗

Effect of ovarian stimulation with recombinant follicle-stimulating hormone, gonadotropin releasing hormone antagonists, and human chorionic gonadotropin on endometrial maturation on the day of oocyte pick-up.

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.

Adult↗

Cortical vesicle breakdown in fertilized eggs of Fundulus heteroclitus.

A scanning and transmission electron microscope study has been made of the cortical alveoli of the egg of Fundulus heteroclitus. The study includes both unactivated eggs and fertilized eggs fixed at intervals of 1 second to 10 minutes after insemination. The alveoli appear to vary considerably in size, in contents, and in morphological aspects of their breakdown. As it undergoes dehiscence, each vesicle may form one or several openings in the egg surface; dense granules and particulate, fibrous, or membranous material, apparently in any combination, are liberated to the nascent perivitelline space. It appears that much of the excess membrane externalized during the reaction is strung out in threads and probably lost to the perivitelline space. The evidence does not suggest that the excess membrane either "dissolves" or is retrieved by the egg cytoplasm. That part of the cortical vesicle membrane which remains continuous with the oolemma gradually becomes microvillous and loses it morphological identity. Granules and particulate matter, presumably liberated from the cortical alveoli, are seen adhering to the inner surface of chorions removed from activated eggs. The micropyle appears to be sealed with similar material. Supernumerary sperm are observed inside the chorion in some instances. The cortical reaction appears to play secondary role in the prevention of polyspermy and to be somehow related to the subsequent formation of a normal embryonic blastodisc.

Animals↗

[Initial results with intratubal embryo transfer].

The intratubal transfer of pronucleus or early cleavage stage embryos (2-8-cell stage) is a new method in the treatment of human infertility. Following transvaginal sonographic oocyte retrieval in vitro fertilization is performed and the fertilized (pronucleus-stage) or embryos are transferred into the tube by laparoscopy. In comparison to GIFT (intratubal gamete transfer) fertilization under in vitro conditions offers the advantage that the success of the fertilization process can be examined. Therefore, this method can give important diagnostic information - especially in cases of poor sperm quality or unexplained infertility. After fertilization in vitro and transfer into the tube the embryone development occurs in the physiological milieu of the oviduct. Up to now the new procedure was performed in 40 patients with male factor or unexplained infertility. In 11 cases (28%) a pregnancy could be achieved. One abortion, but no ectopic pregnancy was observed. No difference in the pregnancy rates could be observed between the transfer of pronucleus stage and the early cleavage stage embryos. This method combines the advantage of IVF and GIFT and offers a successful procedure for the treatment of infertility.

Adult↗

The effect of the duration of GnRH-agonist down regulation before ovarian stimulation on the biological and clinical outcome after intracytoplasmic sperm injection.

The object of this study was to compare the biological outcome (oocyte maturity, fertilization, cleavage) and the clinical outcome after a 'long' (15-24 days) and a 'long-long' (25-40 days) protocol of GnRH-agonist administration for intracytoplasmic sperm injection. Group A consisted of 51 patients with a 15-24-day down regulation period and Group B consisted of 35 patients with a 25-40-day down regulation period, all of which entered ICSI due to severe male factor infertility. Duration and amount of gonadotropin stimulation, serum E2 on the day of hCG administration, number of oocytes retrieved, oocyte maturity, fertilization rate, cleavage rate and pregnancy outcome were comparable for the two groups of patients. Therefore, a flexible period of pituitary desensitization can be employed, allowing us to simplify planning for patients and for the medical staff without affecting the outcome of the trial.

Adult↗

Psychological reactions during in-vitro fertilization: similar response pattern in husbands and wives.

The purpose of this study was to examine differences in daily emotional, physical and social reactions among husbands and wives during in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Forty couples about to undergo ICSI or IVF at a private infertility clinic monitored their emotional, physical and social reactions daily for one complete treatment cycle from the first day of stimulation until the outcome of treatment was known (approximately 35 days). The results showed that men and women had a similar response pattern to oocyte retrieval, fertilization, embryo transfer and the pregnancy test. These stages were associated with the most significant changes in reactions for both spouses. The pattern of results suggested that the most important psychological determinant of reactions during IVF was the uncertainty of treatment procedures. Spouses appeared to be equally sensitive to this uncertainty and both appeared to respond to it with ambivalent feelings involving emotional distress and positive feelings of hope and intimacy.

Adult↗

Impaired reproductive behavior by lack of GluR-B containing AMPA receptors but not of NMDA receptors in hypothalamic and septal neurons.

The roles of ionotropic glutamate receptors in mammalian reproduction are unknown. We therefore generated mice lacking a major subtype of (S)-alpha-amino-3-hydroxy-5-methyl-isoxazolepropionic acid (AMPA) receptors or all N-methyl-d-aspartate (NMDA) receptors in GnRH neurons and other mainly limbic system neurons, primarily in hypothalamic and septal areas. Male mice without NMDA receptors in these neurons were not impaired in breeding and exhibited similar GnRH secretion as control littermates. However, male mice lacking GluR-B containing AMPA receptors in these neurons were poor breeders and severely impaired in reproductive behaviors such as aggression and mounting. Testis and sperm morphology, testis weight, and serum testosterone levels, as well as GnRH secretion, were unchanged. Contact with female cage bedding failed to elicit male sexual behavior in these mice, unlike in control male littermates. Their female counterparts had unchanged ovarian morphology, had bred successfully, and had normal litter sizes but exhibited pronounced impairments in maternal behaviors such as pup retrieval and maternal aggression. Our results suggest that NMDA receptors and GluR-B containing AMPA receptors are not essential for fertility, but that GluR-B containing AMPA receptors are essential for male and female reproduction-related behaviors, perhaps by mediating responses to pheromones or odorants.

Animals↗

Correlation of testicular pathology and sperm extraction in azoospermic men with ejaculated spermatids detected by immunofluorescent localization.

Limiting testicular biopsy for intracytoplasmic sperm injection (ICSI) to those with a high chance of having testicular spermatozoa has not been possible because of the poor predictive value of current clinical and laboratory methods. In order to predict testicular pathology and sperm extraction, we characterised the semen of 28 men with azoospermia due to gonadal failure in terms of the presence of spermatids using an immunological method. The results were compared with the assessment of testicular biopsies by histology and the extraction of spermatozoa into culture medium. Washed cellular elements in the ejaculate were smeared on microscope slides and fixed in 100% methanol, before incubation with acrosome-specific monoclonal antibody (18.6), fluorescein isothiocyanate-labelled anti-mouse goat IgG, and examination by epifluorescent microscopy. Semen from men with oligozoospermia and obstructive azoospermia served as positive and negative controls, respectively. Twelve patients who had positive immunofluorescence (one or more spermatids present) had spermatozoa retrieved from their testes (five hypospermatogenesis, seven focal spermatogenesis), and 16 patients with negative immunofluorescence (spermatids absent) had apparent Sertoli cell-only syndrome (12) or maturation arrest histological pattern (four). However, four patients with apparent Sertoli cell-only syndrome had testicular spermatozoa present after extraction from the biopsy. Plasma follicle stimulating hormone concentration and testicular volume did not predict retrieval of seminal spermatids or testicular spermatozoa. We conclude that the immunofluorescent localization of one or more spermatids in the ejaculate can be used to predict the likelihood of obtaining testicular spermatozoa for ICSI. However, in some patients with Sertoli cell-only syndrome, spermatozoa could still be recovered in the absence of apparent seminal spermatids.

Acrosome↗

Impact of reproductive history on in vitro fertilization and intracytoplasmic sperm injection outcome: evidence from the German IVF Registry.

OBJECTIVE: To evaluate the effect of reproductive history on the outcome of different procedures in assisted reproductive technologies (ART) comparing IVF, ICSI, and cryopreserved embryo transfer (CPE). DESIGN: Prospective registration of ART cycles and their outcomes. SETTING: One hundred three reproductive programs in Germany. PATIENT(S): Women undergoing 174,909 ART procedures from January 1998 through December 2000. INTERVENTION(S): Data analysis of reproductive history collected by the German IVF Registry; multiple logistic regression modeling of success rates. MAIN OUTCOME MEASURE(S): Effect of type of conception and outcome of previous pregnancies, duration of infertility, female's age, and type of ART on clinical pregnancy rate per retrieval. Odds ratios with 95% CIs are reported. RESULT(S): More than one previous pregnancy was negatively correlated with outcome of IVF, ICSI, or CPE. This association disappeared when female age was restricted to a maximum of 35 years. A previous pregnancy achieved by spontaneous conception had less impact on outcome of IVF, ICSI or CPE outcome than did a previous assisted conception. Previous live births and miscarriages demonstrated a statistically significant increase compared with ectopic pregnancies and induced abortions. CONCLUSION(S): Reproductive history must be considered when counseling subfertile couples. Female age, method of conception, and previous pregnancy outcome have a significant effect on IVF, ICSI, and CPE outcome.

Abortion, Spontaneous↗

Female age predicts embryonic implantation after ICSI: a case-controlled study.

From 1 October 1991 until 31 December 1993, 1270 cycles for intracytoplasmic sperm injection were performed. Of these, 71 (5.6%) were carried out in women >/=40 years of age. The semen characteristics in couples >/=40 years of age or <40 years were similar. The mean male age for the older group of women was 47.1 years (range 34-67) versus 35 years (25-71) for the younger group of women (P < 0.001). The mean female age was 41.9 years (range 40-47) and 31.8 years (range 23-39). The numbers of cumulus-oocyte complexes and metaphase-II oocytes were significantly lower in women >/=40 years of age (P < 0.001). The mean numbers of replaced embryos were respectively 2.3 (133/59) in women >/=40 years of age and 2.5 (160/63) in women <40 years of age. The delivery rate per retrieval and per transfer was significantly lower in women >/=40 years of age (P < 0.05). The delivery rates per retrieval and per transfer were respectively 7% (5/71) and 8.5% (5/59) in the older group of women versus 22.5% (16/71) and 25.4% (16/63) in the younger group. Female age is the predictive factor for embryonic implantation.

Adult↗