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Biomedical subjects

S J Muasher

Publications and source records attributed to S J Muasher.

At least 19 recordsLinked to original sources

The significance of hydrosalpinx in in vitro fertilization.

OBJECTIVE: To review the effects of hydrosalpinx on IVF/ET and the role of salpingectomy. DESIGN: The literature on hydrosalpinx, IVF/ET, embryotoxicity, and salpingectomy for hydrosalpinx was identified through MEDLINE searches and reviewed. RESULT(S): Hydrosalpinx has been associated with poor fertility prognosis. IVF/ET is a better alternative to tubal surgery for those patients with severe distal tubal disease, and it is also more cost effective. However, the presence of hydrosalpinx has a negative effect on IVF/ET by decreasing the pregnancy rates and implantation rates compared with patients undergoing IVF/ET for tubal disease but without hydrosalpinx. The hydrosalpingeal fluid has been demonstrated to be embryotoxic to developing embryos, thus leading to increased early pregnancy losses. Poor endometrial receptivity has also been demonstrated in the presence of hydrosalpinges. Removal of the hydrosalpinges leads to improved IVF/ET rates comparable to those patients without hydrosalpinx. Therefore, salpingectomy has been recommended for patients with hydrosalpinx who will be undergoing IVF/ET. CONCLUSION(S): The presence of hydrosalpinx has a negative effect on IVF/ET because of the suspected embryotoxicity of the hydrosalpingeal fluid. Surgical removal of the hydrosalpinx has been shown to improve IVF/ET rates.

Embryo Implantation

Cessation of gonadotropin-releasing hormone agonist therapy combined with high-dose gonadotropin stimulation yields favorable pregnancy results in low responders.

OBJECTIVE: To evaluate the pregnancy results of an ovarian hyperstimulation protocol for IVF-ET that combines GnRH agonist down-regulation, cessation of GnRH agonist therapy with the onset of menstruation, and high-dose gonadotropin administration in low responders. DESIGN: Prospective analysis. SETTING: Academic IVF program. PATIENT(S): One hundred eighty-two low responders undergoing 224 IVF-ET cycles. INTERVENTION(S): Down-regulation was obtained with the administration of leuprolide acetate beginning in the midluteal phase and ending with the onset of menses. Daily administration of 6 ampules of FSH alone or in combination with hMG was initiated on cycle day 3. MAIN OUTCOME MEASURE(S): Stimulation characteristics and pregnancy rates (PRs) were compared between fresh cycles in which pure FSH alone was used and 35 cycles in which a combination of FSH and hMG was administered. RESULT(S): The clinical PR per transfer, the ongoing PR per transfer, and the implantation rate were 32%, 24%, and 9%, respectively. No differences were noted between cycles in which pure FSH alone was used in comparison with cycles in which a combination of FSH and hMG was administered. CONCLUSION(S): Short-term ovarian suppression begun in the luteal phase and discontinued with the onset of menses followed by high-dose stimulation with gonadotropins yields favorable pregnancy results in low responders.

Adult

Impact of fertilization history and semen parameters on ICSI outcome.

PURPOSE: The objectives of this study were (1) to investigate intracytoplasmic sperm injection (ICSI) outcome according to its indications, i.e., a history of failed or poor fertilization and unsuitable sperm parameters for conventional IVF, and (2) to examine the impact of a female's age, sperm concentration, motility, morphology, presence of antisperm antibodies, and hemizona assay (HZA) results on overall outcome. METHODS: Two hundred seventy-nine ICSI cycles performed in 207 couples were retrospectively evaluated. RESULTS: Clinical pregnancy and delivery rates were 36.8 and 29.8% for patients with prior failed fertilization, 23.2 and 17.8% for patients who had prior poor fertilization, and 28.6 and 21.3% for patients with unsuitable sperm parameters. The differences among all groups were found to be insignificant. There was a significant, negative correlation between a female's age and pregnancy results. No difference was found in the three basic sperm parameters between those patients who produced and those who did not produce a pregnancy, but the fertilization rate was significantly higher in patients with more adequate sperm parameters. Although there was a trend toward a better fertilization rate in patients with a hemizona index (HZI) greater than 30 (indicative of a superior sperm-zona pellucida binding capacity) than in those with a HZI less than 30, the difference was not significant. There were no differences in fertilization rate according to the presence or absence of antisperm antibodies. CONCLUSIONS: Fertilization history in a conventional IVF cycle has no effect on success rates following ICSI, and there is no correlation among the basic sperm parameters, the presence of antisperm antibodies, and pregnancy rates.

Age Factors

A prospective, randomized, double-blind study for the evaluation of assisted hatching in patients with advanced maternal age.

The objective of this study was to determine if assisted hatching improved the rates of implantation, clinical pregnancy and ongoing pregnancy for in-vitro fertilization (IVF) patients aged > or =36 years. On the day of oocyte aspiration, consenting patients were randomized according to whether all embryos underwent the hatching procedure (hatched; n = 41) or all embryos remained unhatched (controls; n = 48). Patients in both groups were treated with methylprednisolone and doxycycline starting on the day of oocyte retrieval and continuing for 4 days. The hatching procedure was performed approximately 55 h after insemination on all potential embryos for transfer and employed the release of acidified acid Tyrode's medium against the zona pellucida to create an opening approximately 20 microm in diameter. No significant differences were noted in the mean age, number of oocytes aspirated and number of embryos transferred between the hatched and control groups. In addition, no significant differences were observed in the rates of implantation (11.1 versus 11.3%), clinical pregnancy (39.0 versus 41.7%) and ongoing pregnancy (29.3 versus 35.4%) between the hatched and control groups respectively. These results suggest that assisted hatching may have no significant impact on IVF success rates in the patient population studied.

Adult

The impact of an egg donor's age and her prior fertility on recipient pregnancy outcome.

OBJECTIVE: To investigate the effect of donor's age and her prior fertility on recipient pregnancy outcome in our donor egg program. DESIGN: Retrospective cohort analysis. SETTING: Large academic infertility center. PATIENT(S): A total of 568 fresh ETs were analyzed for the effect of the egg donor's age on pregnancy outcome; a subset of these (n = 185) were analyzed for the effect of the egg donor's prior fertility on pregnancy outcome. INTERVENTION(S): Donors were paired with recipients independent of recipient's age and donor's prior fertility status. MAIN OUTCOME MEASURE(S): Recipient clinical pregnancy rates (PRs) and delivery rates for different donor age groups and for nulligravid donors versus donors with proven fertility. RESULT(S): Donors > or = 33 years old were less likely than younger donors to produce clinical pregnancies and deliveries in their recipients (43.5% versus 26.6% and 35.1% versus 22.1%, respectively). However, there was no difference in clinical PRs or delivery rates between nulligravid donors and donors with proven fertility. CONCLUSION(S): Donors > or = 33 years of age could be excluded from egg donation because of the lower pregnancy potential of their eggs. However, lack of proven fertility in a donor seems to have no negative impact on pregnancy potential.

Adult

Progesterone levels on the day of human chorionic gonadotropin do not predict pregnancy outcome from the transfer of fresh or cryopreserved embryos from the same cohort.

OBJECTIVE: To analyze the differences in pregnancy rates (PRs) from the transfer of fresh and cryopreserved embryos from the same cohort of oocytes based on serum P levels on the day of hCG administration and the day after. DESIGN: Retrospective analysis. SETTING: Infertility patients stimulated for IVF-ET in an academic center. PATIENT(S): Three hundred thirty-three patients with fresh transfer and at least one transfer of cryopreserved embryos from the same cohort of recruited oocytes. All stimulations were down-regulated with a GnRH agonist in a long protocol before gonadotropin stimulation. MAIN OUTCOME MEASURE(S): Clinical PR. RESULT(S): The clinical PR in fresh cycles was 24% for the P < or = 0.9 ng/mL group (group A; conversion factor to SI unit, 3.18) and 34% for the P > 0.9 ng/mL group (group B). Group B patients were younger, received fewer ampules of gonadotropins, had higher peak E2 levels, and had more mature oocytes. There were no significant differences in the P levels on the day of hCG between patients who conceived in both fresh and cryopreserved cycles and any other combination of pregnancy outcome sequence. CONCLUSION(S): These findings suggest that serum P level cutoffs, on the day of hCG and the day after, as a means of making clinical decisions with respect to cancelling the fresh transfer and cryopreservation of all embryos for future transfer should be questioned.

Adult

Transfer of cryopreserved-thawed pre-embryos in a cycle using exogenous steroids without prior gonadotrophin-releasing hormone agonist suppression yields favourable pregnancy results.

We have analysed the use of a programmed cycle of administration of exogenous steroids without prior suppression with a gonadotrophin-releasing hormone agonist (GnRHa) for the transfer of cryopreserved-thawed pre-embryos. From July 1992 to June 1994, 199 cycles (162 patients) were studied. Pre-embryos had been previously cryopreserved at the pronuclear stage using 1.5 M 1,2-propanediol as a cryoprotectant. Preparation of the endometrium was achieved in a step-up regime with transdermal oestradiol patches (0.1 to 0.4 mg). Progesterone in oil (50 mg i.m.) was started on cycle day 13. Pre-embryos were thawed on day 14 and transferred on day 15 after evidence of survival and cleavage. The mean (+/- SD) age of patients undergoing transfer was 35.4 +/- 4.3 years. The mean number of pre-embryos thawed was 4.7 +/- 1.8 with a mean of 3.3 +/- 1.4 pre-embryos being transferred. Eight of the cycles demonstrated follicular development >16 mm prior to thaw and transfer; however, these patients did not demonstrate a luteinizing hormone surge. Mean endometrial thickness on day 13 was 10.8 +/- 2.1 mm. Overall pregnancy rate was 29.2% (57/195). The ongoing or delivery rate was 16.1% (32/195). The rate of preclinical losses per transfer was 6.2% (12/195). Overall, the implantation rate was 6.2% (47/757). Thus, the use of a programmed cycle for cryopreserved embryo transfer yields favourable pregnancy outcome and offers practical advantages to patients. Prior suppression with a GnRHa is not necessary for endometrial preparation.

Adult

Cryopreservation of all prezygotes in patients at risk of severe hyperstimulation does not eliminate the syndrome, but the chances of pregnancy are excellent with subsequent frozen-thaw transfers.

In-vitro fertilization patients (n = 15) at risk of ovarian hyperstimulation syndrome (OHSS) (oestradiol > or =4500 pg/ml on the day of human chorionic gonadotrophin administration and 25 or more follicles of intermediate or large size) underwent aspiration of all follicles and cryopreservation of all fertilized oocytes at the pronuclear stage. Patients were monitored for up to 2 weeks post-retrieval. Subsequent transfer of cryopreserved-thawed embryos was performed in programmed cycles using exogenous oestrogen and progesterone for endometrial preparation. Two patients (13%) developed OHSS necessitating hospitalization and vaginal aspiration of ascitic fluid. Two other patients (13%) developed moderate OHSS requiring ascitic fluid vaginal aspiration in the office setting, with dramatic improvement of the condition. Subsequent transfer of cryopreserved-thawed embryos yielded a clinical pregnancy rate of 58% per transfer and ongoing or delivery rates of 42 and 67% per transfer and per patient respectively. By eliminating pregnancy potential with cryopreservation of all prezygotes and examining the pregnancy potential with subsequent cryopreserved-thawed transfers, it is concluded that OHSS is reduced, but not eliminated for patients at risk. Subsequent transfer of cryopreserved-thawed prezygotes in a programmed cycle with exogenous steroids yields an excellent pregnancy rate.

Adult

Improved oocyte quality is obtained with follicle stimulating hormone alone than with follicle stimulating hormone/human menopausal gonadotrophin combination.

The aim of this study was to compare the efficacy of pure follicle stimulating hormone (FSH) with that of FSH/human menopausal gonadotrophin (HMG) combination in downregulated cycles. A total of 357 patients was evaluated retrospectively. Sixty percent of patients in the FSH group and 55% in the FSH/HMG group were new; the others were repeat patients. Ovulation was suppressed with leuprolide acetate in all patients, followed by either FSH (n = 218) or FSH/HMG (n = 119). There was no difference in patients' age, infertility factors, number of ampoules used, length of stimulation, oestradiol levels on day of human chorionic gonadotrophin (HCG) administration, number of oocytes recovered or the number of embryos transferred. Also, nuclear maturity at aspiration and fertilization rates were not different between the two groups. FSH stimulation resulted in a significantly higher percentage of mature oocytes that showed the typical 'mature' morphological characteristics (P < 0.0001). The clinical pregnancy rates per transfer were 40 and 28% in patients stimulated with pure FSH and FSH/HMG respectively (P < 0.05). The significantly higher number of immature oocytes matured in vitro in the FSH/HMG group (P = 0.001) suggests a possible effect on in-vitro maturation, due to luteinizing hormone present in HMG. The difference in mature oocyte quality may be an important determinant in the higher pregnancy rates for the FSH-stimulated patients.

Chorionic Gonadotropin

The incidence of multiple gestations after in vitro fertilization is dependent on the number of embryos transferred and maternal age.

OBJECTIVE: To determine if the incidence of multiple gestations after IVF differs significantly depending on the number of embryos transferred and maternal age. DESIGN: Retrospective analysis of IVF database. SETTING: Tertiary care academic center. PATIENTS: One thousand eight hundred sixty-seven patients undergoing IVF with up to four embryos transferred during 1986 through 1993. MAIN OUTCOME MEASURES: The rate of singleton and multiple gestations > 20 weeks estimated gestational age (EGA). RESULTS: The incidence of triplet gestations > 20 weeks EGA among patients < or = 34 years of age with three versus four embryos transferred was 0.3% (1/335) versus 2.4% (15/662), respectively. The incidence of twin gestations > 20 weeks EGA among patients < or = 34 years of age with two versus four embryos transferred was 1.3% (3/234) versus 7.4% (46/622), respectively. Also among patients < or = 34 years of age, the incidence of singleton gestations > 20 weeks EGA with two versus three embryos transferred was 12.8% (30/234) versus 15.8% (53/335); with two versus four embryos was 12.8% (30/234) versus 17.2% (107/622); and with three versus four embryos was 15.8% (53/335) versus 17.2% (107/622), respectively. CONCLUSIONS: In women < or = 34 years of age undergoing IVF-ET, the transfer of four versus three and four versus two embryos significantly increased the incidence of triplet and twin gestations, respectively, without significantly improving the chance of singleton conception. This implies that a policy of transferring only three embryos should be considered in this age group (realizing that such a policy may merit modulation if pretransfer embryo selection is used.).

Adult

Salpingectomy improves the pregnancy rate in in-vitro fertilization patients with hydrosalpinx.

The objective of this study was to assess the impact on pregnancy outcome of excising hydrosalpinx(ges) in patients with repeated in-vitro fertilization (IVF) failures. A group of 15 patients who had previously undergone failed IVF attempts and had unilateral or bilateral hydrosalpinx was subjected to an operative laparoscopy with excision of the affected tube(s). Of these, 10 patients underwent a unilateral salpingectomy and five had a bilateral salpingectomy. Stimulated cycles of IVF and/or cryo-thaw cycles were then carried out post-salpingectomy and the results were compared to those of pre-salpingectomy cycles. There was no statistically significant difference between the number of mature eggs retrieved, peak oestradiol concentrations, number of days to human chorionic gonadotrophin administration, or number of pre-zygotes frozen in the stimulated cycles pre- versus post-salpingectomy. Pre-salpingectomy, 15 patients underwent 38 stimulated cycles and eight patients underwent 14 cycles with cryopreserved-thawed embryos, achieving one pregnancy from a fresh transfer that resulted in a miscarriage. Post-salpingectomy, eight patients underwent 12 stimulated cycles, achieving five clinical pregnancies (two miscarriages and three ongoing pregnancies, i.e. either delivered or a pregnancy > or = 20 weeks), and nine patients underwent 10 cycles with cryopreserved-thawed embryos, achieving four clinical pregnancies (one miscarriage and three ongoing). We conclude that excision of hydrosalpinx(ges) improves the pregnancy potential after IVF, and that new and repeat IVF patients should be counselled accordingly.

Adult

A comparative analysis of embryo implantation potential in patients with severe teratozoospermia undergoing in-vitro fertilization with a high insemination concentration or intracytoplasmic sperm injection.

The objective of this study was to assess fertilization, implantation and pregnancy rates in infertile patients with severe teratozoospermia [P (poor prognosis) pattern sperm morphology assessed by strict criteria] treated by in-vitro fertilization (IVF) using a high insemination concentration (HIC), or by intracytoplasmic sperm injection (ICSI). This was a retrospective cohort study performed in an academic tertiary institution. The outcome of 115 consecutive ICSI cycles was compared to that of a similar number of cycles of IVF with HIC performed during a similar time frame and matched by woman's age and basal serum (cycle day 3) follicle stimulating hormone concentrations. The inclusion criteria were sperm morphology </=4% normal forms (P pattern) and >/=1x10(6) total motile spermatozoa per ejaculate. The diploid fertilization rate in the HIC-IVF group was 86% and in the ICSI group 68% (P < 0.05). Importantly, an equal number of embryos was transferred to both groups of patients. The morphological quality of the embryos (proportion of transfers having superior morphology embryo scores) was significantly better in the ICSI group than in the patients receiving HIC-IVF. Although there was a clear trend for better implantation and pregnancy rates in the ICSI group, these differences were not statistically significant. We conclude that, although HIC-IVF resulted in a higher fertilization rate than ICSI in patients with severe teratozoospermia, ICSI produced a significantly higher proportion of morphologically superior embryos with a tendency towards a higher implantation potential. Therefore, teratozoospermic patients having adequate numbers of motile spermatozoa should be offered ICSI as an alternative to modified (HIC) IVF treatment.

Cohort Studies

Suppression and flare regimens of gonadotropin-releasing hormone agonist. Use in women with different basal gonadotropin values in an in vitro fertilization program.

OBJECTIVE: To evaluate the suppression and flare regimens of gonadotropin-releasing hormone agonist (GnRH-a) in ovarian hyperstimulation in women with variable basal gonadotropin values in an in vitro fertilization (IVF) program. STUDY DESIGN: A retrospective study comparing the initiation of GnRH-a in the midluteal phase of the preceding cycle (suppression protocol) and follicular phase of the stimulated cycle (flare protocol) in women with basal follicle-stimulating hormone (FSH) values < 15 mIU/mL and > or = 15 mIU/mL. RESULTS: The pregnancy rate per initiated cycle and implantation rate for women with basal FSH levels > or = 15 mIU/mL were 20.4% and 9.8% in flare GnRH-a cycles and 11.7% and 3.5%, respectively, in suppression GnRH-a cycles. Comparing the percent differences in clinical pregnancy and implantation rates between both protocols for women with different basal FSH values, pregnancy outcome was significantly greater in the flare protocols in women with values > or = 15 mIU/mL (P < .001). Individualization of the stimulation protocol by retrospective sorting of women undergoing IVF with respect to their basal gonadotropin levels significantly improved clinical pregnancy (P < .05) and implantation rates (P < .05) and reduced the cancellation rate (P < .05). CONCLUSION: The flare regimen with GnRH-a is a useful alternative for controlled ovarian hyperstimulation in women with elevated basal FSH values (> or = 15 mIU/mL) undergoing IVF.

Adult

Low-dose glucocorticoids after in vitro fertilization and embryo transfer have no significant effect on pregnancy rate.

OBJECTIVE: To determine the effect on pregnancy rate (PR) of low-dose glucocorticoid treatment in cycles without micromanipulation. DESIGN: Randomized, prospective, double-blinded, placebo-controlled trial. SETTING: One university-based tertiary infertility center and two private infertility centers. PATIENTS: All patients receiving standard stimulation IVF-ET or transfer of cryopreserved embryos at the participating facilities from January to September 1993 were asked to participate in this study. Patients having micromanipulation were excluded from this study. INTERVENTIONS: Participating patients were randomized to either 16 mg oral 6-alpha-methylprednisolone for four evenings starting the evening of retrieval or the evening before thawing cryopreserved embryos or to placebo administered in an identical fashion. Both groups were treated with 250 mg oral tetracycline four times per day starting with initiation of the study medication and continuing for 4 days. Cryopreservation and stimulation cycles were managed according to pre-established protocols for all patients. A clinical pregnancy was confirmed by an appropriately rising hCG titer and a gestational sac on ultrasound. RESULTS: A total of 206 stimulation patients and 61 cryopreservation patients were randomized and had an ET. Patient characteristics were similar between groups. The clinical pregnancy and implantation rates between placebo and glucocorticoid groups were 35.9% versus 40.8% and 12.8% versus 11.7% for stimulation cycles and 30.3% versus 25% and 9.9% versus 7.4% for cryopreservation cycles, respectively. None of these differences were statistically significant. CONCLUSIONS: Glucocorticoid plus antibiotic treatment at these doses for transfers of nonmicromanipulated embryos does not appear to have a significant effect on pregnancy or implantation rates.

Adult

Evaluation of the spindle apparatus of in-vitro matured human oocytes following cryopreservation.

The present study was conducted to determine if the cryopreservation of immature human oocytes has a deleterious effect on the meiotic spindle following maturation in vitro. Oocytes were obtained in excess from in-vitro fertilization patients and divided into four groups. Groups 1 (n = 98) and 2 (n = 80) consisted of immature oocytes cryopreserved before or after maturation in vitro respectively. Groups 3 (n = 37) and 4 (n = 9) served as non-frozen controls and included oocytes matured in vitro and in vivo respectively. The meiotic spindle was identified after incubation in anti-tubulin monoclonal antibody (1 h, 37 degrees C) and fluorescein-conjugated goat anti-mouse immunoglobulin G (IgG) (1 h, RT). Chromosomes were counterstained with 4',6'-diamidino-2-phenylindole. Following cryopreservation, group 1 oocytes demonstrated a 63% survival rate and 68% maturation rate in vitro. In all, 58% of the oocytes in group 2 survived the thaw. The number of oocytes with normal spindles in group 1 (81.0%) was not significantly different from control groups 3 (83.8%) and 4 (88.9%), while the number of group 2 oocytes with normal structures (43.5%) was significantly lower than groups 1 (P = 0.0004), 3 (P = 0.0002), and 4 (P = 0.025). These results suggest that cryopreservation of the prophase I human oocyte does not significantly increase abnormalities in the resulting meiotic spindle.

Cell Survival

Cryopreservation: the problem of evaluation.

A simple evaluatory formula for reporting pregnancy rates involving cryopreserved material has so far remained elusive. It is highly desirable to have a method which would allow not only an evaluation of cryotechnology per se, but also an evaluation of the role of cryotechnology in enhancing the total reproductive potential of a single cycle. In this paper, nine separate formulae are described which can be used for the evaluation of cryopreservation. It is concluded that none of the existing formulae used alone expresses the total potential of cryopreservation, and that while each formula provides information regarding some aspect of the role of cryopreservation, the most comprehensive evaluation requires the answer to five different equations. The other four formulae, while often used, are regarded as providing information which is unsubstantiated or does not allow complete evaluation.

Cryopreservation