Doria H. Harris

Multivariate Analysis of Factors Predictive of Successful Live Births in In Vitro Fertilization (IVF) Suggests Strategies to Improve IVF Outcome

Purpose:Our purpose was (1) to identify characteristics correlated with pregnancy outcome, (2) to use these characteristics to predict in vitro fertilization (IVF) outcome, and (3) to develop strategies that might improve IVF success.Methods:Maternal age, cause for IVF, donor insemination, rank of attempt, serum estradiol and luteinizing hormone levels on the day of human chorionic gonadotropin administration, flexible vs rigid catheter, number of embryos transferred of each morphologic type, and cell number were analyzed by logistic regression.Results:Variables positively correlated with success are as follows: (1) for pregnancy, endometriosis and 2-, 3-, and 4-cell good and 4-cell excellent embryos: (2) for live births, 2-, 3-, and 4-cell good and 4-cell excellent embryos and donor insemination; and (3) for multiple births, 2- and 4-cell good and 4-cell excellent embryos. Maternal age was negatively correlated with live births.Conclusions:Embryos derived from IVF have different potentials for implantation, live births, and multiple births. Transferring one additional good-quality embryo for each 5 years of incremental increase in maternal age is predicated to improve live birth rates without increasing multiple births.

Assessment of day-3 morphology and euploidy for individual chromosomes in embryos that develop to the blastocyst stage.

OBJECTIVE To examine the relationship between day-3 morphology and euploidy for individual chromosomes in embryos that develop to the blastocyst stage by day 5. DESIGN Retrospective cohort study. SETTING Boston IVF, a large university-affiliated reproductive medicine practice. PATIENT(S) Ninety-nine patients undergoing their first preimplantation genetic screening (PGS) cycle between January 1 and December 31, 2006. INTERVENTION(S) In vitro fertilization (IVF) and preimplantation genetic screening (PGS). MAIN OUTCOME MEASURE(S) Prevalence of euploidy for chromosomes X, Y, 8, 13, 14, 15, 16, 17, 18, 20, 21, and 22 in day-3 high implantation potential (HIP) versus non-HIP embryos that grew to day-5 blastocysts. RESULT(S) Seven hundred three embryos from 99 cycles in 99 patients underwent PGS. Three hundred sixty-four (52%) embryos from 88 cycles in 88 patients developed to the blastocyst stage by day 5. High implantation potential embryos were more likely to be euploid for chromosomes X/Y, 8, 15, 16, 18, and 22 compared with non-HIP embryos, with similar trends for chromosomes 14 and 17. There were no statistically significant differences between HIP and non-HIP embryos in euploidy prevalence for chromosomes 13, 20, and 21. CONCLUSION(S) Our data suggest that PGS may detect potentially viable but detrimental chromosomal abnormalities that are not detected by embryo morphology alone.

Microscopic epididymal sperm aspiration (MESA): A new option for treatment of the obstructive azoospermia associated with cystic fibrosis

Cystic fibrosis is a life-threatening disease. Only recently has the prognosis improved. In the male patient there is an almost invariable absence or maldevelopment of the vas deferens, creating a situation of obstructive azoospermia. Consequently, their fertility potential has been considered nonexistent. Having gained experience in microscopic epididymal sperm aspiration coupled with the advanced reproductive technologies for the treatment of congenital absence of the vasa, we sought to extend this treatment option to the male cystic fibrosis population. An Indian male with clinically evident and genetically confirmed cystic fibrosis underwent microscopic retrieval of epididymal sperm. The anatomy of the epididymis and the quality of sperm obtained were similar to those patients with congenital absence of the vas deferens. After appropriate spousal genetic testing, superovulation, and transvaginal oocyte retrieval, in vitro insemination of sperm was performed. Fifty percent of the oocytes were subjected to partial zona dissection and a single embryo resulted. Subsequent to transfer, no conception was realized but the effort expanded the clinical usefulness of microscopic epididymal sperm aspiration. This should open up an avenue of treatment for couples in whom only the most dire predictions for fertility have been made to date.

Subcutaneous versus intramuscular administration of human chorionic gonadotropin during an in vitro fertilization cycle.

OBJECTIVE To confirm that hCG levels in follicular fluid and serum would be comparable between i.m. and s.c. administration of purified hCG. DESIGN In a prospective study, serum and follicular fluid levels of hCG after an i.m. or s.c. injection of 10,000 IU of hCG were evaluated 36 hours after injection, that is, at the time of oocyte retrieval. SETTING This study was carried out in a university-affiliated IVF program. PATIENT(S) Forty women undergoing oocyte retrieval were entered into the study at the time of egg retrieval, that is, 36 hours after hCG administration. INTERVENTION(S) S.c. or i.m. injection of hCG. MAIN OUTCOME MEASURE(S) Serum and follicular fluid concentrations of hCG were evaluated 36 hours after injection at the time of oocyte retrieval. RESULT(S) There was a significantly higher serum hCG level in the s.c. group (348.6 +/- 98 IU/L) vs. the i.m. group (259.0 +/- 115 IU/L) and a significantly higher follicular fluid hCG level in the s.c. vs. the i.m. group (233.5 +/- 85 vs. 143.4 +/- 134 IU/L). CONCLUSION(S) After purified hCG administration via the s.c. route, both serum and follicular fluid levels are greater compared with the i.m. route.

Sperm morphology and in vitro fertilization outcome: a direct comparison of World Health Organization and strict criteria methodologies**Presented in part at the Meeting of the American Urological Association, San Antonio, Texas, May 15 to 20, 1993.

OBJECTIVE To perform a direct comparison of two sperm morphology methodologies with regard to IVF outcome. DESIGN Blinded comparison of two methods of morphology assessment using the same morphology slides. PATIENTS Data were obtained from 132 couples in a consecutive series of patients undergoing IVF. MAIN OUTCOME MEASURES Two practical end points were selected for analysis for each couple: the presence of any fertilization and the number of fertilized eggs. Normal traditional morphology was defined as > or = 40% normal forms in a sample and normal strict criteria was defined as > or = 4%. RESULTS Traditional morphology demonstrated a higher sensitivity and negative predictive value than strict criteria (87% versus 61%, and 68% versus 36%, respectively). Positive predictive value and specificity were also numerically greater but did not reach statistical significance. Abnormal traditional morphology, but not strict criteria, was associated with reduced fertilization even among samples with normal sperm concentration and motility. Samples with normal morphology were associated with a greater number of fertilized eggs per couple than those with abnormal morphology: this difference was 3.2 fertilized eggs for traditional morphology and 1.6 for strict criteria. Overall, for samples with < 40% by traditional morphology only one case yielded more than two fertilized eggs. In contrast, up to five fertilized eggs were noted for the lowest strict criteria scores. CONCLUSIONS Comparison of traditional morphology and strict criteria with regard to IVF outcome favored traditional morphology in several areas. In particular, low scores were more predictive of poor IVF outcome.