Clomid in unexplained infertility.
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Biomedical subjects
Publications and source records attributed to J H Check.
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OBJECTIVE: To determine whether either the use of intracytoplasmic sperm injection (ICSI) or chymotrypsin-galactose pretreatment of sperm before IUI can improve pregnancy results in female partners of men with sperm with subnormal hypo-osmotic swelling test scores. DESIGN: Randomized controlled study. SETTING: University-based private practice of an infertility center and IVF center. PATIENT(S): Couples with infertility who presented during a specific time interval and in whom the male partner had a hypo-osmotic swelling score of < 50% in two consecutive cycles. INTERVENTION(S): Controls were treated by conventional IUI. Members of the treatment group were given an option of treatment of sperm with chymotrypsin-galactose before undergoing IUI or of undergoing IVF-ET with ICSI. MAIN OUTCOME MEASURE(S): Pregnancy rate (PR) per patient and per cycle. RESULT(S): None of the 14 control patients conceived despite 38 IUI cycles, whereas conception occurred for 4 (50%) of 8 couples in whom sperm was pretreated with chymotrypsin-galactose and for 2 (50%) of 4 couples who underwent ICSI. Patients who had enzymatic sperm treatment underwent 12 IUI cycles and 4 ICSI cycles; the PR per cycle was 33.3% in the former and 50% in the latter. CONCLUSION(S): These data suggest that treating sperm with chymotrypsin-galactose before IUI or injecting only one sperm into the oocyte overcomes to some degree the block to successful pregnancy seen in women whose male partners have subnormal hypo-osmotic swelling tests.
OBJECTIVE: To evaluate whether oligoasthenozoospermia may lead to a higher spontaneous abortion (SAB) rate once a pregnancy is established by IVF-ET. DESIGN: Retrospective clinical observational study. SETTING: University-based IVF program. PATIENT(S): Three hundred sixty-four couples with normal semen parameters who underwent IVF-ET with conventional sperm incubation; 70 couples with oligoasthenozoospermia but without marked abnormal sperm morphology (< 4% normal forms using strict criteria) who underwent ET after IVF with conventional sperm incubation; and 20 couples with oligoasthenozoospermia but without abnormal sperm morphology who underwent ET after IVF with intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S): Implantation rate, clinical pregnancy rate, SAB rate, and delivery rate after IVF-ET. RESULT(S): Despite similar pregnancy and implantation rates per ET, as a result of a higher SAB rate (40.0% versus 11.7%), the delivery rates were lower in the female partners of men with oligoasthenozoospermia. Similar patients who used ICSI had a 0% SAB rate. CONCLUSION(S): Oligoasthenozoospermia should be considered a possible risk factor for SAB in IVF achieved pregnancies. Further studies are needed to determine whether ICSI reduces the risk of SAB associated with oligoasthenozoospermia.
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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.
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The objective of this study was retrospectively to evaluate both in-vitro fertilization (IVF) and non-IVF cycles in which the male partner had been taking calcium channel blockers, either to confirm or refute previous data from another centre, suggesting that these drugs cause a severe but reversible subfertility problem in the male. These drugs were found to inhibit expression of mannose-ligand binding receptors, thus preventing spermatozoa from attaching to the zona pellucida; they were postulated to cause failed fertilization based on one case having this defect, in whom a return to normal was achieved after stopping the drug. However, the couple did not undergo a cycle with IVF to see if fertilization now occurred. The data presented here demonstrated fertilization in all patients having IVF who were taking calcium channel blockers. The subsequent pregnancy rate per transfer was 17.4%. Also, five out of 11 (45.4%) non-IVF patients conceived after correction of various female factors. Failure of the other six patients to conceive could be explained by other confounding factors, especially oligoasthenozoospermia. Taking into consideration other data suggesting poor fertilization when this mannose-ligand binding receptor abnormality was demonstrated, we propose the possibility that this defect, when not associated with calcium channel blockers, may be associated with some other cryptic factor that causes poor fertilization. According to our hypothesis, calcium channel blockers might cause the problem in mannose expression but also adversely affect some other factor that is deficient when non-drug related abnormalities in mannose-ligand binding expression are found.
PROBLEM: To determine if allogenic stimulation from leukocyte immunization (LI) can increase the production of an immunomodulatory protein called progesterone induced blocking factor (PIBF) by CD8+ T-lymphocytes. METHODS: The study group consisted of 35 women, 29 who failed to conceive after repeated embryo transfers (ETs) and six with recurrent spontaneous abortion (RSA). The women underwent LI using the the male partner's blood as the source of leukocytes. Progesterone induced blocking factor was measured pre- and post-LI with an immunocytochemistry method using a PIBF-specific polyclonal antibody. RESULTS: The mean percentage of lymphocytes expressing PIBF, as well as the percentage of cases of whose PIBF level increased to 1% or more, was significantly higher post-LI, Similarly post-LI, there was a significantly lower percentage of zero PIBF levels. CONCLUSIONS: Leukocyte immunization causes an increase in PIBF in many cases. Possibly the improved pregnancy outcome in immunized patients with RSA or previous failure to conceive with in vitro fertilization may be partially or possibly completely explained by its stimulatory effect on PIBF.
PROBLEM: The objective of this study was to evaluate the correlation of menstrual CA-125 levels with pregnancy rates (PRs) after 6 months of treatment for infertility. METHOD: The sample consisted of a heterogenous group of 160 women who sought treatment for infertility. Treatments include progesterone supplementation, donor insemination, intrauterine insemination, and ovulation induction therapy. No laparoscopies were done during the study period. A baseline CA-125 level was drawn during menses before the initiation of therapy. Patients were followed for 6 months of treatment or until a pregnancy was achieved. RESULTS: There was no difference in the 6 month PR or viable PR by CA-125 level. CONCLUSIONS: Elevated CA-125 levels are not predictive of poor fertility potential at least during the first 6 months of infertility therapy. Even though these higher levels sometimes suggest that endometriosis is present, the data suggest that correction of male factor, cervical factor or ovulation factor provides effective PRs without the need for laparoscopic intervention.
PROBLEM: An immunomodulatory protein known as the progesterone induced blocking factor (PIBF) has been found to positively correlate with early pregnancy beta human chorionic gonadotropin (B-hCG) levels. The study presented herein evaluated PIBF levels from conception to the end of the first trimester to determine if lower levels will correlate with first trimester spontaneous abortions (SAB). METHOD: Progesterone induced blocking factor expression by lymphocytes measured using an immunocytochemistry method was compared in pregnant women with ongoing vs. failed pregnancies. RESULTS: There were no differences in the proportion of women having lymphocytes expressing PIBF or in the median numbers when comparing ongoing vs. failed pregnancies. There was no B-hCG interval where failed pregnancies were found to have lower frequency of PIBF expressing lymphocytes. CONCLUSION: Inadequate PIBF expression independent of low P levels does not appear to be an etiologic factor for first trimester SABs; thus measuring this protein in pregnant women lacks practical usefulness.
PROBLEM: To compare the expression by T-lymphocytes of an immunomodulatory protein known as progesterone-induced blocking factor (PIBF) in conception versus non-conception cycles even when there has been definite fertilization and embryo formation. METHOD: PIBF expression on T lymphocytes was measured using an immunohistochemical method with a PIBF-specific polyclonal antibody. These levels were determined in patients undergoing three types of therapy: non-in vitro fertilization (IVF), IVF-embryo transfer (ET), and frozen ET. Sera were drawn 12 days from ovulation in non-IVF cycles or 9 days after ET and were assayed for PIBF and beta human chorionic gondotropin. Comparison of the frequency of lymphocyte expression of PIBF in pregnant versus non-pregnant women were made. RESULTS: PIBF was detected in 29.5% of non-pregnant women and 52.5% of pregnant women. There were no differences in PIBF levels by therapy used in non-pregnant cases or in the pregnant group. CONCLUSION: These data are consistent with the hypothesis that maternal expression of PIBF in T-lymphocytes soon after trophoblast invasion may depend on successful implantation.
The study presented herein evaluated whether 26 of 122 consecutive women who tend to hyper-respond (serum estradiol >4,000 pg/ml or >30 follicles) following controlled ovarian hyperstimulation for in vitro fertilization have higher serum FSH levels at certain critical stages during the follicular phase. Baseline day-2 serum FSH and blood levels taken on days 5 and 6 of human menopausal gonadotropin therapy were not different in the hyper-responders from those responding normally. The only significant difference in serum FSH was seen on the day of human chorionic gonadotropin where it was actually lower in the hyper-responders. Thus, there does not appear to be a critical serum FSH level which would dictate a decrease in gonadotropins to prevent hyper-response.
The study presented herewith was designed to compare the pregnancy and abortion rates in patients treated with gonadotropin preparations with and without LH content based on data suggesting that higher serum LH levels during the follicular phase may reduce subsequent pregnancy rates and increase spontaneous abortion rates. Infertile patients with luteal phase defects related to releasing eggs prior to complete follicular maturation were treated with either ultra-low dose (75 IU) hMG or pure FSH. The pregnancy rates for first treatment cycles for hMG versus pure FSH was 22.7% and 20.3%, respectively. The spontaneous abortion rates were also similar (8.0% and 9.1%). There were no multiple births resulting from these 36 pregnancies. Ovarian hyperstimulation syndrome was not observed in any of the 164 stimulation cycles. Thus these results show no advantage in choosing a preparation devoid of LH therefore giving the patient the opportunity to purchase the least expensive medication that is available.
The high rate of multiple gestations following ovulation induction with and without assisted reproductive technologies (ART) has led to an increased interest in selective reduction. The aim of this study was to compare pregnancy outcome of 6 triplet and 2 quintuplet pregnancies following selective reduction to twins to a group of 30 natural twin pregnancies delivered during the same time period. Outcome variables compared included birth weights, gender, gestational age at delivery, route of delivery, and neonatal complications. Results failed to demonstrate an adverse effect of selective reduction on pregnancy outcome.
The objective of this study was to determine whether there were differences in gestational age markers in dizygotic twin pregnancies resulting from in vitro fertilization-embryo transfer (IVF-ET) when compared with dizygotic twin pregnancies spontaneously conceived following ovulation inducing therapy drugs without assisted reproductive techniques (ART). Thirty-one sets of twins conceived by IVF-ET and 33 sets of twins conceived without ART were monitored by serum beta human chorionic gonadotropin (B-hCG) levels and transvaginal sonographic measurements of sac size (SS) and crown-rump length (CRL). Comparison between groups found that SS was significantly smaller in the IVF-ET group as compared to the non-ART group 21-35 days post-ovulation (p < .05). The CRL was similar in both groups as well as the doubling times of B-hCG. These data indicate that in dizygotic twin pregnancies initial development of SS may be slower following IVF-ET than in spontaneously conceived twins.
PURPOSE: Our purpose was to determine if pronuclear-stage embryos (2PN) could be thawed, then frozen again with subsequent survival and cleavage after thawing. METHODS: A simplified cryopreservation protocol was used in which a slow cooling program is started at the seeding temperature of -6 degrees C in an alcohol-bath controlled-rate freezer. 1,2-Propanediol (1.5 M) was added to embryos before cooling. A fast thawing technique at room temperature was used. The cryoprotectant was removed in one step using a 1 M sucrose solution. RESULTS: Three months after refreezing, the three 2PN embryos were thawed and all three cleaved after 24 hr in culture. Following embryo transfer a pregnancy was achieved and a healthy full-term baby girl was born. CONCLUSIONS: This is the third case reported of successful pregnancies after transfer of human embryos that were frozen twice before transfer and the first case where the second freeze occurred at the pronuclear stage. This is also the first successful refreezing of human embryos using a simplified freezing and thawing technique with one-step addition and removal of cryoprotectant.
OBJECTIVE: To investigate the relationship of early follicular phase serum LH levels and pregnancy rates in ovulatory women with regular menstrual cycles. METHODS: One hundred consecutive couples seeking help for infertility who had bilateral tubal patency, a minimum motile sperm-density-of 2.5 million/mL, and regular menstrual cycles were enrolled in the study. Baseline serum measurements of LH, FSH, and testosterone were obtained before treatment. Patients were treated with clomiphene citrate, human menopausal gonadotropin, or progesterone supplementation, as needed. Treatment continued for 6 months or until conception occurred. The 6-month pregnancy rates were correlated with baseline early follicular phase serum levels and age. RESULTS: The 6-month viable pregnancy rates did not decrease with an increase in baseline LH serum levels; they were 50% if LH was 10 mIU/L or less, 15.3% if LH was 11-20 mIU/mL, and 71.4% if LH was more than 20 mIU/mL. The 16.7% pregnancy rate in women whose baseline FSH exceeded 25 mIU/mL was significantly lower than the 56.3% rate in women whose FSH was 25 mIU/mL or lower. The pregnancy rates also declined significantly with age. When we controlled for age, FSH did not have an independent effect on conception rates. CONCLUSION: Early follicular phase serum levels of LH were not associated with pregnancy rates in infertile ovulatory women who were treated with progesterone in the luteal phase when needed. However, early follicular levels of FSH and age at treatment were found to be related to pregnancy rates.
OBJECTIVE: To compare clinical pregnancy and implantation rates after transfer of frozen-thawed embryos prepared according to an assisted hatching protocol or a nonassisted hatching protocol. DESIGN: A historical cohort study in which a cohort of patients who underwent an assisted hatching protocol was matched for clinical parameters to an external historical cohort treated before assisted hatching was available. SETTING: In vitro fertilization-ET facility of a university-based practice. PATIENTS: Seventy-nine matched pairs. INTERVENTIONS: Nonassisted hatching patients: embryos were thawed, cultured in human tubal fluid + 0.5% bovine serum albumin until 48 hours and transferred. Assisted hatching patients: embryos thawed, cultured in human tubal fluid + 10% synthetic serum substitute until 72 hours, had assisted hatching and transferred. MAIN OUTCOME MEASURES: Clinical pregnancy (gestational sac) and implantation rates. RESULTS: Twelve (15.2%) clinical pregnancies per transfer in nonhatched group versus 24 (30.4%) in hatched group. Nonhatched group: 284 embryos transferred; 15 (5.3%) implanted. Three pregnancies (25.0%) had two sacs. Hatched embryos: 269 were transferred; 37 (13.7%) implanted. Eleven pregnancies (45.8%) were multiple gestations (9 twins, 2 triplets). CONCLUSION: Clinical pregnancy and implantation rates were higher for group having assisted hatching protocol. It is not clear whether the improvement is due to the overall methodology change or to assisted hatching. Assisted hatching using the zona-drilling technique is not detrimental to frozen-thawed human embryos and may be beneficial.