Richard W. Tureck

Effect of follicular size on oocyte retrieval, fertilization, cleavage, and embryo quality in in vitro fertilization cycles: a 6-year data collection

OBJECTIVE To determine the effect of follicular size, including the size of the leading follicle, on oocyte retrieval, fertilization, cleavage, and embryo quality in IVF cycles based on a large data collection. DESIGN Retrospective analysis of 1,109 IVF cycles between 1987 and 1993 at the Hospital of the University of Pennsylvania including 606 patients ranging in age from 23 to 49 years. RESULTS Follicles with a volume < or = 1 mL show a significantly lower oocyte recovery rate than follicles with a volume of > 1 mL. The highest recovery rate (83.5%) was found in follicles with a volume of 3 to 4 mL. Above a follicular volume of 7 mL, the oocyte recovery drops below that observed for follicles between 1 and 7 mL. Fertilization and cleavage rates were also higher in oocytes obtained from follicles > 1 mL compared with follicles < or = 1 mL. Although fertilization rates were fairly stable above volumes of 1 mL, cleavage rates continued to rise to a peak percentage of 92% with volumes between 6 and 7 mL. Leading follicle size did not have an effect on fertilization and cleavage rates of cohort oocytes. Embryo quality was not influenced significantly by follicular volume. CONCLUSION Based on this evaluation of a large number of follicles, follicular size is a useful indicator of oocyte recovery, fertilization, and cleavage in IVF cycles. For optimal results, the follicular fluid volume in gonadotropin- and hCG-stimulated cycles should be > 1 mL, which corresponds to a follicle diameter of > 12 mm, and not larger than 7 mL (24 mm). For timing of hCG administration, the number of adequate size follicles appears to be more important than the size of the leading follicle(s).

Perceptions of infertility and treatment stress in females as compared with males entering in vitro fertilization treatment

OBJECTIVE To determine gender similarities and differences in perceptions of infertility and anticipated treatment stress in couples enrolling for in vitro fertilization (IVF) treatment. DESIGN Both partners were evaluated at enrollment of IVF treatment. The evaluation was part of the screening procedure. SETTING The Department of Obstetrics and Gynecology at a teaching hospital. PATIENTS, PARTICIPANTS Two hundred consecutive couples who entered an IVF treatment program. MAIN OUTCOME MEASURES Self-report questionnaire included items on the duration of infertility, degree of social support, effect of infertility on sexual relationship, expected likelihood of achieving pregnancy, anticipation of stress during treatment, and a self-rating scale of emotional reactions to infertility. RESULTS The women anticipated more stress in IVF treatment but also rated greater degree of social support than the men. Both partners overestimated their chances of a successful treatment outcome. Factor analysis of the Infertility Scale produced three factors that were similar for both sexes. The first factor represented the desire to have a child as a major focus of life with inadequacy of the male role, social functioning and work efficiency, and pressure to have a child following. CONCLUSIONS Women reported more stress, but the factors affecting stress of infertility were very similar for both partners. The intense focus on having a child was the predominant factor in anticipated stress of IVF treatment for both males and females.

The zona-free hamster egg penetration assay as a prognostic indicator in a human in vitro fertilization program *

The present study was designed to test the validity of the hamster egg penetration assay as a prognostic indicator of male fertility in 54 patients undergoing in vitro fertilization. Human oocyte fertilization, cleavage, and pregnancy were compared with the results of this bioassay. Good correlation was found between hamster egg penetration and oocyte fertilization. Conversely, a definite lower limit of hamster egg penetration to define absolute male infertility could not be established because human oocyte fertilization, cleavage, and even pregnancy occurred in spite of low hamster egg penetration.

Emotional and Psychosocial Factors in Follow‐Up of Women After Ivf‐Et Treatment: A pilot investigation

One hundred and fifty‐six women who enrolled for treatment in an in vitro fertilization (IVF‐ET) program were interviewed, 15 months (mean interval) after the last program contact. Perceptions of treatment stress, decisions about further treatment and the extent of resolution of the infertility crisis were investigated. Standard self‐report instruments were used to assess emotional status, self‐esteem and marital adjustment. The results showed that only about half the couples who did not achieve pregnancy had decided to terminate treatment. Resolution of infertility was significantly correlated with coping with infertility and with the decision to abandon treatment. Although most patients described treatment as extremely stressful, this did not itself result in emotional distress or dysfunction following treatment, and psychiatric syndromes were infrequent. A deeper understanding of the interactions of these identified factors would help all couples who confront unwanted infertility.

Sequential analysis of zona thickness during in vitro culture of human zygotes: correlation with embryo quality, age, and implantation.

Zona pellucida thickness was measured daily in zygotes and cleavage stage embryos. Measurements were performed on a Nikon inverted microscope equipped with Hoffman modulation optics, using an ocular micrometer. Zona thickness of each zygote/embryo was measured four times, the zygote/embryo was then “rolled over,” and four more measurements were repeated for a total of eight. The zygotes/embryos were photographed daily and the measurements repeated on the prints. Subsequently, the mean zona thickness for each stage was calculated. A total of 81 patients (mean age 33.8 ± 4.2) participated in the study. A total of 427 embryos were evaluated. Categorical data differences between groups were evaluated by ANOVA and multiple linear regression. For nominal data, the Kruskal‐Wallis test was applied; when P < 0.05 the differences were considered to be significant. We found that the average zona thickness on day 1 of in vitro culture was 17.7 ± 0.14 μm; 16.3 ± 0.14 μm on day 2 and 14.9 ± 0.14 μm on day 3 (P < .0001). When the zona thickness was analyzed in relation to the number of blastomeres on day 3 of culture, there was a highly significant correlation with blastomere number (P < .0001). Similarly, there was a highly significant correlation with embryo grade (P < .005) and fragmentation (P < .001). The data were also analyzed for embryos transferred that resulted in a successful pregnancy, revealing that embryos in a pregnancy cycle had significantly thinner zonae pellucidae (P < .0001), when compared to embryos that were not transferred or from nonconceptual cycles. The average zona thickness also decreased with age, and was most apparent after 35 years. Changes in zona thickness correlated with the number of blastomeres, grade, fragmentation, age and were more evident in embryos transferred from cycles resulting in successful pregnancies. Therefore, zona pellucida measurements should be included in the overall assessment of embryo quality, since this information may be useful in the selection of optimal embryos for transfer. Mol. Reprod. Dev. 47:99–104, 1997.

Follicular maturation parameters associated with the failure of oocyte retrieval, fertilization, and cleavage in vitro

Follicular maturation parameters predictive of decreased success in human in vitro fertilization were evaluated in 104 gonadotropin-stimulated cycles. Falling estradiol (E2) levels correlated with decreased fertilization (1.9 oocyte/cycle) and cleavage (1.4 oocyte/cycle), when compared with cycles with increasing E2 (2.4 and 2.1 oocyte/cycle, respectively). Likewise, polyspermic fertilization was higher in the former group. Falling E2 levels after human chorionic gonadotropin (hCG) administration correlated with similar trends. Delaying hCG (24 to 96 hours) relative to the last dose of gonadotropin did not affect the total number of oocytes fertilized per cycle. However, polyspermic fertilization and cancellation rates were higher. Leading follicles growing beyond 2.3 cm (determined by ultrasound examination) were associated with decreased recovery, fertilization, and cleavage, and increased polyspermic fertilization. We conclude that ultrasonography and E2 monitoring can predict decreased fertilization and cleavage and should also be monitored after hCG administration.

Analysis of the human zona pellucida during culture: Correlation with diagnosis and the preovulatory hormonal environment

Purpose: The objective of this study was to analyze sequentially the human zona pellucida changes in an in vitro fertilization program as it relates to several variables.Methods: The zona pellucida thickness was measured daily in zygotes and cleavage-stage embryos on a Nikon inverted microscope equipped with Hoffman modulation contrast optics, using an ocular micrometer. A total of 512 embryos from 96 patients was evaluated.Results: There was a highly significant direct correlation between zona thickness and preovulatory estradiol and basal day 3 FSH levels (P < 0.02 andP < 0.0006, respectively). This relationship showed a rapid reversal following 48 hr of culture; embryos from patients with the highest FSH levels had thinner zonae prior to transfer (P < 0.0007). The zonae from patients with unexplained infertility were thicker (19.4 ± 2.7 µm) than those from patients with endometriosis (17.7 ± 2.2 µm), tubal (17.5 ± 2.4 µm), or male-factor infertility (16.4 ± 2.7 µm) (P < 0.0001) on the first day of culture.Conclusions: We hypothesize that the thickness of the human zona pellucida is influenced by the preovulatory hormonal environment and diagnosis. These factors should be considered as part of the embryo quality evaluation prior to transfer or when assessing the possibility of using assisted hatching. More studies are needed to understand the factors regulating the thickness of the human zona pellucida.

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.

Simultaneous ectopic pregnancy with intrauterine twin gestations after in vitro fertilization and embryo transfer.

A simultaneous ectopic tubal pregnancy with viable intrauterine twin gestations after IVF-ET of five fertilized eggs is presented. Pelvic ultrasound and serial quantitative hCG levels were not helpful in the diagnosis of the tubal pregnancy. The risk of multiple pregnancies and of concomitant intrauterine and extrauterine gestations increases with transfer of a greater number of embryos. Karyotype of the tubal pregnancy was normal (46,XX).

Ovarian response to human menopausal gonadotropin following suppression with oral contraceptives

The main conclusion of this study is that a profound suppression of the pituitary and ovary can be associated with an inadequate response which may require a longer or different regimen of stimulation to achieve the desired outcome for IVF. We suggest that a pretreatment determination of E2 and gonadotropins can be of value to predict the nature of ovarian response in women with suppressed pituitary-ovarian function.