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Successful pregnancy and delivery after calcium ionophore oocyte activation in a normozoospermic patient with previous repeated failed fertilization after intracytoplasmic sperm injection.

To describe a successful pregnancy and delivery after calcium ionophore oocyte activation in a normozoospermic patient with previous repeated failed fertilization after intracytoplasmic sperm injection (ICSI).Case report. In vitro fertilization unit in a university affiliated medical center.A couple with 5 years of unexplained primary infertility who had repeated failed fertilization after ICSI. Controlled ovarian hyperstimulation, oocyte pick-up, ICSI, assisted oocyte activation with calcium ionophore, embryo culture, and ET. Fertilization rate, implantation, pregnancy, and delivery. Assisted oocyte activation with calcium ionophore A23187 after ICSI resulted in reasonable fertilization rates in three cycles (4/6, 5/16 and 7/20 oocytes). Two pregnancies were achieved; the first ended with second trimester miscarriage due to fetal anomaly and the second with a delivery of three healthy babies.Calcium ionophore oocyte activation seems to be a useful method in cases of repeated failed fertilization after ICSI.

Adult↗

The relationship of tubal blockage, infertility of unknown cause, suspected male infertility, and endometriosis to success of in vitro fertilization and embryo transfer.

The success of in vitro fertilization (IVF) and embryo transfer has been examined with regard to five categories of infertility over a 2-year period. Fertilization rates in vitro were highest in women with bilateral tubal blockage and women treated for endometriosis. There was a significant reduction of approximately 13% in the fertilization rate of couples with idiopathic infertility and women who had failed to conceive after 12 cycles of artificial insemination by donor. A further substantial reduction in the fertilization rate occurred when the husband had low quality semen, particularly when no abnormality was detected in the wife. Repeated IVF in couples with idiopathic infertility eventually resulted in fertilization. It is recommended that donor spermatozoa not be used for cases of idiopathic infertility, but it may be needed in cases of poor semen quality. There were no differences in the pregnancy rates following embryo replacement in any of the groups studied, nor was there any detectable effect of age on fertilization or pregnancy rates up to the age of 44 years.

Adult↗

In vitro fertilization: a treatment for male infertility.

Three-quarters of 41 women whose husbands were the cause of infertility in the couple had one or more embryos replaced after in vitro fertilization. One-third became pregnant despite their long history of infertility; the incidence of pregnancy was 45% after one or more replacements of embryos. In a group of 61 couples where both partners were infertile, 26% became pregnant. These data indicate that the lower chance of fertilization with poor semen is balanced by a higher chance of pregnancy in women with a normally functioning reproductive system. Oligospermia, asthenospermia, teratospermia, and autoimmunity are among the many forms of male infertility which can now be successfully treated by in vitro fertilization. Overall, 57% of the oocytes were fertilized, and almost 50% of men with very low numbers of active spermatozoa (less than or equal to 0.5 X 10(6)/ml motile spermatozoa) were successful in establishing pregnancy. Two semen parameters impaired fertilization most: seminal inflammatory cells and low progressive activity. The collection of split ejaculates and the careful preparation of spermatozoa, by sedimentation and layering methods, proved to be beneficial, improving sperm motility and raising the chance of fertilization.

Embryo Transfer↗

Fertilization and cleavage after reinsemination of human oocytes in vitro.

The results of reinsemination of 150 morphologically mature oocytes that failed to fertilize within 15 to 20 hours after initial insemination were evaluated. Only 41 oocytes (27.3%) were fertilized after reinsemination, which is significantly lower than the percentage obtained after initial insemination (74%). However, the cleavage rate was not impaired significantly. Polyspermic fertilization was common (17 oocytes, 29.3%). A total of 64 oocytes were transferred. In 18 patients, all of the oocytes that were transferred had been reinseminated; none of these patients conceived. However, of 28 patients who received embryos arising from both initial insemination and reinsemination protocols, 7 conceived (25%). We suggest that the percentage of fertilization is impaired after 22 hours of incubation in vitro and that those oocytes that have fertilized after reinsemination might partly reflect a misjudgment of initial oocyte maturity. Nevertheless, reinsemination is a relatively simple procedure, with no known attributed risk. Therefore, we recommend reinsemination to increase the overall fertilization percentage. Additional studies are needed to establish better methods for assessment of oocyte maturity to evaluate properly the benefit of such reinsemination procedures.

Cleavage Stage, Ovum↗

Sperm morphologic features as a prognostic factor in in vitro fertilization.

To determine whether there is a prognostic value in the percentage normal sperm morphologic features in a human in vitro fertilization (IVF) program, the authors conducted a prospective study in women with bilateral tubal damage. Based on the percentage of morphologically normal spermatozoa, the patients were divided into four groups: group I, normal morphologic features between 0% and 14%; group II, 15% to 30%; group III, 31% to 45%; and group IV, 46% to 60%. One hundred ninety successful laparoscopic cycles were evaluated. In group I, 104 oocytes were obtained, of which 37% fertilized, but no pregnancy resulted; in group II, 81% of 324 oocytes were fertilized, with a pregnancy rate per embryo transfer (ET) of 22%; in group III, 82% of 309 oocytes were fertilized, with a 31% pregnancy rate; and in group IV, 91% of 69 oocytes were fertilized, with a pregnancy rate of 12%. Probability models indicated that there was a clear threshold in normal sperm morphologic features at 14%, with high fertilization and pregnancy rate in the groups with normal sperm morphologic features greater than 14%.

Embryo Transfer↗

Androstenedione and progesterone concentrations in preovulatory follicular fluid correlate with successful fertilization and cleavage of human oocytes in vitro.

OBJECTIVE: To determine if androstenedione (A) and progesterone (P) concentrations in preovulatory follicular fluid (FF) correlate with successful fertilization and cleavage of human oocytes in vitro. DESIGN: A retrospective randomized trial. SETTING: Hospital department of obstetrics and gynecology. PATIENTS: Fifty-five patients, ages 24 to 39 years, with normal menstrual cycles undergoing in vitro fertilization (IVF) for tubal infertility. INTERVENTIONS: Multiple follicular development was induced with clomiphene citrate and human menopausal gonadotropin. MAIN OUTCOME MEASURES: Relationships among FF steroid hormone, morphological maturity of oocyte-corona-cumulus complexes, and fertilization and cleavage of oocytes. RESULTS: Follicles with mature oocyte-corona-cumulus complexes and unfertilized oocytes contained significantly greater amounts of A (P less than 0.05) than those with mature oocyte-corona-cumulus complexes and fertilized ova, indicating the occurrence of atretic changes. Follicles yielding successfully fertilized and cleaved ova had significantly greater amounts of P (P less than 0.05) and A (P less than 0.01) but similar levels of 17 beta-estradiol compared with follicles yielding fertilized ova that failed to cleave. CONCLUSIONS: Follicles yielding oocytes that cleaved as a result of IVF have both a shift in steroidogenesis from estrogen to progestin accumulation and declining aromatase activity, thus reflecting progressive luteinization of the follicles.

Adult↗

Prediction of in vitro fertilization outcome by sperm penetration assay with TEST-yolk buffer preincubation.

OBJECTIVE: To evaluate sperm penetration assay (SPA) value as a screening tool before in vitro fertilization (IVF). DESIGN: Follow-up study comparing sperm variables and IVF outcome. SETTING: Infertile couples in an academic research environment. PATIENTS, PARTICIPANTS: Two hundred forty-one infertile couples scheduled for IVF. INTERVENTIONS: Sperm penetrating assay with cold Tes-TRIS (TEST) Yolk buffer semen preincubation and IVF. MAIN OUTCOME MEASURES: Percent of egg penetration recoded into poor and good category (0% to 20%, 21% to 100%) and compared with fertilization, embryo transfer, and pregnancy rate (PR) in IVF, as well as sperm count motility and morphology. RESULTS: Sperm penetrating assay predicted fertilization with a high negative (74%) and positive (82%) predictive rate and good specificity value (0.96). One of 31 patients in the poor SPA category (3%) fertilized less than 50% of eggs; no pregnancy occurred. In the good SPA category, 87 of 210 patients (41%) fertilized greater than or equal to 50% of eggs with 34.3% PR. Sperm penetrating assay correlated better with fertilization rate than did sperm count and motility but not morphology. CONCLUSIONS: Sperm penetrating assay is a useful screening assay before IVF together with sperm morphology.

Adult↗

Subzonal multiple sperm injection in the treatment of previous failed human in vitro fertilization.

OBJECTIVE: To assess the value of subzonal sperm injection in previous failed spontaneous in vitro fertilization (IVF). DESIGN: Prospective study on patients with at least one cycle of previous failed spontaneous IVF. SETTING: Human Reproductive Biology Unit, Soliman Fakeeh Hospital, Jeddah, Saudi Arabia. PATIENTS: Thirty-nine patients with prolonged infertility with at least one previous cycle of failure of spontaneous fertilization of any oocyte. RESULTS: Seventy-eight of 276 oocytes successfully injected with three to four sperms were fertilized. Fertilized rate was 28.2%. Polyspermy was observed in 6 (8%) of the fertilized oocytes. Sixty-six (92%) of the 72 with monospermic fertilization cleaved normally and were replaced in the uterine cavity. Pregnancy occurred in 6 (23%) of the women who had embryos replaced. CONCLUSIONS: Multiple sperm injection into the oocyte subzonal space should be considered for the treatment of patients with previous failed spontaneous IVF.

Adult↗

Sperm characteristics and outcome of human assisted fertilization by subzonal insemination and intracytoplasmic sperm injection.

OBJECTIVE: To investigate the influence of sperm characteristics on the treatment by subzonal insemination (SUZI) and intracytoplasmic sperm injection of couples with severe male infertility. DESIGN: A retrospective analysis of 300 consecutive cycles of assisted fertilization concerning 202 infertile couples was performed. One hundred fifty-three couples underwent 362 unsuccessful IVF cycles, whereas on 49 couples IVF was not performed because of poor sperm characteristics. SETTING: Procedures were performed in an institutional research environment. PATIENTS, PARTICIPANTS: Couples in which the male partner was the presumed cause of repeated failure to achieve conception by IVF or in which seminal parameters were unacceptable for IVF. INTERVENTIONS: Three hundred transvaginal oocyte retrievals were performed after superovulation by GnRH agonist and gonadotropins. MAIN OUTCOME MEASURES: After SUZI and intracytoplasmic sperm injection the following parameters were evaluated: fertilization, cleavage, pregnancy, and implantation rates in relation to the sperm parameters and the proportion of acrosome-free spermatozoa after different treatments. RESULTS: Normal fertilization occurred in 18% of the oocytes treated by SUZI and in 44% after intracytoplasmic sperm injection. Only the treatment by electroporation showed a positive correlation with the fertilization rate. Fourteen pregnancies were obtained after SUZI, 8 pregnancies after intracytoplasmic sperm injection, and 8 pregnancies after a combination of the two procedures. A score calculated from the sperm parameters after selection correlated with the fertilization obtained after SUZI, whereas a score calculated from the parameters before sperm selection correlated with the pregnancy rate. Sperm morphology influenced the implantation rate of the embryos obtained with these two procedures. CONCLUSIONS: Intracytoplasmic sperm injection and SUZI can successfully treat couples who fail IVF or who cannot benefit from IVF. Different treatments can be applied to semen samples to increase the number of acrosome-reacted spermatozoa. The few significant relations found between sperm characteristics and the outcome of assisted fertilization cannot predict the outcome.

Adult↗

Human menopausal gonadotropin during in vitro maturation of human oocytes retrieved from small follicles enhances in vitro fertilization and cleavage rates.

OBJECTIVES: To compare the IVF rates of oocytes retrieved from small follicles (< 2 mL in volume) with those of oocytes retrieved from large follicles and to test the effect of adding gonadotropins to the IVF medium on the fertilization rates of oocytes from small follicles. DESIGN: Oocytes were retrieved with endovaginal ultrasound (US) guidance from patients undergoing infertility treatment in our IVF program. Oocytes were grouped according to the volume of the originating follicle and subjected to our routine procedure for IVF. HMG was added to the IVF medium for some of the oocytes from small follicles. SETTING: Toronto Fertility and Sterility Institute is affiliated with the University of Western Ontario and University of Toronto and is equipped for RIA, endovaginal US monitoring and oocyte retrieval, and for processing and culturing gametes and embryos. PATIENTS: Infertile patients admitted to our IVF program. INTERVENTIONS: Patients underwent ovarian stimulation with hMG before oocyte retrieval. No other interventions were introduced to the processing and culturing the gametes and embryos except the addition of hMG to the medium of some of the small follicle-originated oocytes with the informed consent from the patients. MAIN OUTCOME MEASURES: Rates of fertilization, cleavage of the fertilized embryos before replacement, and meiotic status of some of the oocytes from small follicles. RESULTS: Most of the oocytes from small follicles did not complete the first meiotic division; they had low rates of fertilization and cleavage compared with oocytes from large follicles, and these rates were improved by the addition of hMG to the IVF medium. CONCLUSIONS: Oocytes from small follicles are probably less mature and require a more physiological environment to achieve normal rates of fertilization and cleavage.

Adult↗

Levels of CA-19.9, CA-125, and CA-195 in seminal plasma and in vitro fertilization rates.

OBJECTIVE: To assess the relationship between carbohydrate tumor markers in seminal plasma and fertilization rates in IVF cycles. DESIGN: Prospective study. SETTING: Academic tertiary hospital. PATIENTS: Forty-six consecutive couples subjected to IVF in which at least one oocyte was obtained. MAIN OUTCOME MEASURES: Determination of CA-19.9, CA-125, and CA-195 in seminal plasma 1 week before IVF. RESULTS: CA-125 was higher in the group without fertilization (321 +/- 198 U/mL, mean +/- SD) than in the group in which at least one oocyte was fertilized (155 +/- 165 U/mL), whereas CA-19.9 and CA-195 were similar in both groups. However, at the cutoff 66%, lower values of CA-19.9 were found in the fertilization group rate < 66% (707 +/- 1,217 versus 1,069 +/- 1,084) and of CA-195 (67 +/- 44 versus 218 +/- 274). No correlation was found between tumor marker levels and fertilization rates. CONCLUSION: CA-125 seems to be an indicator of sperm fertilization capacity, whereas the importance of CA-195 and CA-19.9 will require further studies.

Antigens, Tumor-Associated, Carbohydrate↗

Poor fertilization may be related to oocyte or zona pellucida recognition defects specific to certain hyperstimulation regimens and limited to some males but not others: a case report.

OBJECTIVE: To determine if the controlled ovarian hyperstimulation (COH) regimen may cause sperm to appear subfertile only to improve considerably by changing the COH protocol. DESIGN: Case report with retrospective review of previous fertilization rates according to COH protocol used. MAIN OUTCOME MEASURES: Fertilization and pregnancy rates (PRs) after IVF-ET. RESULTS: Known fertile donor sperm failed to fertilize any of 11 oocytes compared with 14 of 18 for processed retrograde ejaculate using the same oocyte pool. Retrospective analysis of other cycles for different female patients but same donor found 16.6% fertilization rate whenever luteal phase leuprolide acetate (LA)-hMG regimen was used compared with 70.6% with short-flare regimen. CONCLUSION: Some COH regimens may cause oocyte or zona pellucida changes that create recognition defects for some sperm but not others. Interestingly, the sperm with the binding defect with the luteal phase LA-hMG COH protocol exhibited good fertilization rates with oocytes prepared with the short-flare protocol and demonstrated high in vivo PRs after IUI.

Adult↗

Cystic fibrosis gene mutations do not affect sperm function during in vitro fertilization with micromanipulation for men with bilateral congenital absence of vas deferens.

OBJECTIVE: To assess the effects of cystic fibrosis transmembrane-conductance regulator (CFTR) gene mutations on sperm function and fertility in men with bilateral congenital absence of the vas deferens. DESIGN: Prospective. SETTING: Division of urologic microsurgery and associated hospital-based IVF unit. MAIN OUTCOME MEASURES: Fertilization and pregnancy rates. PATIENTS: Men referred to our fertility unit for treatment of bilateral congenital absence of the vas deferens, using sperm surgically retrieved from the epididymis with IVF and micromanipulation. RESULTS: Of 45 men with bilateral congenital absence of the vas, 54% (19/35) tested were found to be carriers of CFTR gene mutations, with one compound heterozygote. Epididymal sperm from men affected with CFTR mutations fertilized 19% (29/152) of oocytes, whereas men without mutations fertilized 22% (44/204) of oocytes. Pregnancy rates (PRs) were 36% (5/14) for cycles involving men with CFTR mutations and 33% (5/15) for other patients with congenital absence of the vas deferens but without detectable CFTR mutations. CONCLUSIONS: The presence of detectable CFTR mutations does not affect fertilization rates or PRs for men with bilateral congenital absence of the vas deferens when IVF and micromanipulation are applied.

Cystic Fibrosis↗

Fertilization rates using intracytoplasmic sperm injection are greater than subzonal insemination but are dependent on prior treatment of sperm.

OBJECTIVE: To determine a suitable method of sperm preparation for use in micromanipulation. To compare the fertilization rates of sibling oocytes inseminated by intracytoplasmic sperm injection (ICSI) and subzonal insemination (SUZI). DESIGN: Two methods of gamete micromanipulation to overcome male factor infertility were compared. Within this study, three trials were conducted to determine the most suitable method of sperm preparation. This method then was used to complete the study. SETTING: Procedures were performed in a teaching hospital research environment. PATIENTS: Ninety-six patients were recruited for this study, undergoing 99 stimulation cycles. INTERVENTIONS: Sibling oocytes were inseminated by subzonal sperm or intracytoplasmic injection. MAIN OUTCOME MEASURES: Fertilization, zygote development, and pregnancy rates. RESULTS: In the absence of manipulative pretreatment of sperm (trial 1), there was no difference in normal fertilization rates between ICSI and SUZI (19% and 25%, respectively). In the second trial there again was no sperm pretreatment for SUZI but, for ICSI, a polyvinylpyrrolidone (PVP) solution was used to reduce sperm velocity and the sperm tails were incised before injection. The fertilization rates were significantly different between ICSI (44%) and SUZI (17%). In the third trial, PVP was added to the sperm used for both types of insemination and the sperm tails also were incised for the ICSI insemination. Fertilization was again significantly different (16% for SUZI and 44% for ICSI). The trial 2 method of sperm preparation then was used to complete the study (trial 4) and confirmed the results of trial 2 (21% for SUZI and 42% for ICSI). The results suggest that ICSI can give improved fertilization compared with SUZI provided the sperm are treated before injection. No significant differences were found in the development rates of zygotes suitable for transfer or cryopreservation between the two micromanipulation methods.

Cytoplasm↗

The value of oocyte reinsemination in human in vitro fertilization.

The value of oocyte reinsemination in human in vitro fertilization (IVF) was evaluated in this study. Two groups of 25 cycles each were studied. In group 1 cycles, insemination of mature/questionably mature oocytes (judged by cumulus and corona cell appearance) at 6.5 hours postcollection yielded a fertilization rate of 42.3%. This value was significantly lower than that obtained with reinsemination (70.8%). In group 2, questionably mature oocytes were treated as immature and inseminated 24 to 30 hours postcollection. The fertilization rate of mature eggs in group 2 was 68.2%, with a reinsemination success rate of 40%. Triploidy rates and cleavage rates of mature eggs, fertilized either at initial insemination or reinsemination and of fertilized immature eggs, were similar within group 1 and group 2 cycles. In group 1, two pregnancies resulted from transfer of embryos arising solely from successful reinsemination, with one infant delivered. These results indicate that reinsemination offers a useful adjunct for IVF in cases where fertilization failure occurs.

Embryo Transfer↗

First and subsequent pregnancies after tubal microsurgery: evaluation of the fertility index.

OBJECTIVE: To determine the number of children born after a tubal microsurgical operation and to evaluate the fertility index, a long-term measure of reproductive potential. DESIGN: A case series involving a follow-up questionnaire. SETTING: A tertiary care university hospital. PATIENT(S): Three hundred twelve women undergoing microsurgery for tubal disease. INTERVENTIONS: A range of open microsurgical procedures including reversal of sterilizations. MAIN OUTCOME MEASURE(S): Cumulative pregnancy rates to the first and second normal pregnancies and calculation of the fertility index. RESULT(S): The 2-year cumulative pregnancy rates (probability +/- SE) for a first normal pregnancy for proximal disease, distal disease, tubal reanastomoses, and tubal adhesions were 0.51 +/- 0.05, 0.29 +/- 0.06, 0.47 +/- 0.06, and 0.30 +/- 0.07, respectively. Of the 288 (92%) women responding to the questionnaire, 142 women had at least one child. Of the 100 women who wanted a second child, 68 succeeded, the proportions being similar in each surgery category. The fertility index described restoration of normal fertility in 30%, 12%, 34%, and 23% for women with proximal disease, distal disease, anastomotic procedures, and adhesion disease, respectively. CONCLUSION(S): The fertility index is a useful measure of long-term reproductive potential. The high recurrent pregnancy rate emphasizes the value of microsurgery in restoring normal fertility to some women.

Adult↗

The feasibility of assessing women's perceptions of the risks and benefits of fertility drug therapy in relation to ovarian cancer risk.

OBJECTIVE: To determine the feasibility of asking women undergoing fertility treatment the maximum increased risk of ovarian cancer they would be willing to tolerate in order to take ovulation-induction drugs. DESIGN: A prospective pilot study of women attending fertility clinics over a 2-month period. SETTING: Two tertiary care fertility clinics in Toronto. PATIENT(S): Sixty-one English-speaking women were approached and 85% (n = 52) were enrolled. INTERVENTION(S): A self-administered questionnaire with fertility-specific questions. Thirty-eight women also were asked to complete standardized scales of anxiety and optimism. MAIN OUTCOME MEASURE(S): Women's report of the maximum level of lifetime risk of ovarian cancer they were willing to tolerate in order to undergo fertility treatment. RESULT(S): Seventy-nine percent were willing to accept an increased risk of ovarian cancer. Only 24% understood that treatment for ovarian cancer usually was not curative. CONCLUSION(S): A majority of patients were willing to tolerate a modest increase in their lifetime risk of ovarian cancer because of fertility treatment, most basing their estimate of acceptable risk on limited awareness of the issue.

Adult↗

Even more extreme fertility insurance and the sex ratios of protozoan blood parasites.

Theory developed for malaria and other protozoan parasites predicts that the evolutionarily stable gametocyte sex ratio (z*; proportion of gametocytes that are male) should be related to the inbreeding rate (f) by the equation z*=(1-f)/2. Although this equation has been applied with some success, it has been suggested that in some cases a less female biased sex ratio can be favoured to ensure female gametes are fertilized. Such fertility insurance can arise in response to two factors: (i) low numbers of gametes produced per gametocyte and (ii) the gametes of only a limited number of gametocytes being able to interact. However, previous theoretical studies have considered the influence of these two forms of fertility insurance separately. We use a stochastic analytical model to address this problem, and examine the consequences of when these two types of fertility insurance are allowed to occur simultaneously. Our results show that interactions between the two types of fertility insurance reduce the extent of female bias predicted in the sex ratio, suggesting that fertility insurance may be more important than has previously been assumed.

Animals↗