D. Summers-Chase

Controlled Ovarian Hyperstimulation Adversely Affects Implantation Following In Vitro Fertilization–Embryo Transfer

Purpose:Our purpose was to determine if controlled ovarian hyperstimulation adversely affects implantation.Methods:A retrospective comparison of pregnancy rates (PRs) and implantation rates was made between oocyte recipients versus their donors, who shared half of the retrieved oocytes, and regular patients undergoing in vitro fertilization–embryo transfer (IVF-ET) who were not sharing eggs.Results:Higher implantation rates (39.0 vs 22.5%; P < 0.05) were found in recipients compared to donors in the stimulated cycle. However, no differences were seen in PRs or implantation rates in frozen ET cycles. The data for standard IVF patients were almost-identical to those for donors.Conclusions:Superior implantation rates and PRs in oocyte recipients versus donors were not related to better oocyte quality for recipients because of egg sharing or to a better uterine environment because of similar results with frozen ET in all three groups. An adverse effect of the hyperstimulation regimen best explains the difference.

ICSI AS AN EFFECTIVE THERAPY FOR MALE FACTOR WITH ANTISPERM ANTIBODIES

This study was conducted to evaluate if in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) is an effective treatment for infertility complicated by the presence in the male partner of sperm autoantibodies. Over a 1-year study period comparisons of fertilization, pregnancy, and implantation rates were made in couples where the male partner was negative or weakly positive for sperm autoantibodies (<50%) (gr 1); autoantibodies were strongly positive (>80%) (gr 2); or autoantibodies were moderately positive (50-80%) (gr 3). Only patients having oocytes fertilized by ICSI were included. The fertilization, clinical pregnancy, implantation, and miscarriage rate for group 1 (n = 67) was 56, 43, 21, and 14%. Comparable values for group 2 (n = 20) were 55, 40, 23, and 25%, and for group 3 (n = 6) were 63, 33, 23, and 0%. IVF with ICSI demonstrates comparable fertilization, pregnancy, implantation, and miscarriage rates in female partners of males with and without sperm autoantibodies.This study was conducted to evaluate if in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) is an effective treatment for infertility complicated by the presence in the male partner of sperm autoantibodies. Over a 1-year study period comparisons of fertilization, pregnancy, and implantation rates were made in couples where the male partner was negative or weakly positive for sperm autoantibodies (<50%) (gr 1); autoantibodies were strongly positive (>80%) (gr 2); or autoantibodies were moderately positive (50-80%) (gr 3). Only patients having oocytes fertilized by ICSI were included. The fertilization, clinical pregnancy, implantation, and miscarriage rate for group 1 (n = 67) was 56, 43, 21, and 14%. Comparable values for group 2 (n = 20) were 55, 40, 23, and 25%, and for group 3 (n = 6) were 63, 33, 23, and 0%. IVF with ICSI demonstrates comparable fertilization, pregnancy, implantation, and miscarriage rates in female partners of males with and without sperm autoantibodies.

A RANDOMIZED STUDY COMPARING THE EFFECT OF STANDARD VERSUS SHORT INCUBATION OF SPERM AND OOCYTE ON SUBSEQUENT PREGNANCY AND IMPLANTATION RATES FOLLOWING IN VITRO FERTILIZATION EMBRYO TRANSFER

Some data suggest that some sperm are associated with a toxic product that lowers embryo implantation rates when these sperm come in contact with the zona pellucida. The possibility exists that shortening the incubation time could improve pregnancy rates. A randomized prospective study was initiated to evaluate pregnancy and implantation rates with transfer of embryos formed by conventional overnight vs short (2-h) co-incubation of sperm and oocytes. The clinical and viable pregnancy rates were 41 and 29% for conventional co-incubation versus 30 and 30% for short co-incubation. Implantation rates were also similar (17.9 vs 17.8%). Short incubation does not seem to impact any advantage over conventional co-incubation techniques in couples undergoing in vitro fertilization where the male factor is normal.Some data suggest that some sperm are associated with a toxic product that lowers embryo implantation rates when these sperm come in contact with the zona pellucida. The possibility exists that shortening the incubation time could improve pregnancy rates. A randomized prospective study was initiated to evaluate pregnancy and implantation rates with transfer of embryos formed by conventional overnight vs short (2-h) co-incubation of sperm and oocytes. The clinical and viable pregnancy rates were 41 and 29% for conventional co-incubation versus 30 and 30% for short co-incubation. Implantation rates were also similar (17.9 vs 17.8%). Short incubation does not seem to impact any advantage over conventional co-incubation techniques in couples undergoing in vitro fertilization where the male factor is normal.

SPERM EXTRACTED AND CRYOPRESERVED FROM TESTES SEVERAL HOURS AFTER DEATH RESULTS IN PREGNANCY FOLLOWING FROZEN EMBRYO TRANSFER: CASE REPORT

A 38-year-old male died suddenly on his honeymoon. Sperm was extracted from his testes 3 h following his death and cryopreserved. His wife had in vitro fertilization (IVF) and the eggs were inseminated by intracytoplasmic sperm injection (ICSI). None of the sperm were motile. Selection was based on softness and pliability. There were 4 embryos formed that cleaved, but only 2 were transferred on the retrieval cycle. The wife failed to conceive, but then had a second transfer of the 2 cryopreserved embryos. She achieved a chemical pregnancy with the beta-human chorionic gonadotropin level attaining a maximum level of 107 mIU/mL (rising from 19 mIU/mL). Though this retrieval cycle did not result in a successful pregnancy the achievement of a clinical pregnancy following frozen embryo transfer at least provides cautious optimism for other cases with similar conditions.

AN EVALUATION OF THE EFFICACY OF IN VITRO FERTILIZATION WITH INTRACYTOPLASMIC SPERM INJECTION FOR SPERM WITH LOW HYPOOSMOTIC SWELLING TEST SCORES AND POOR MORPHOLOGY

AbstractPurpose: To corroborate or refute a previous study demonstrating that in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) is an effective therapy for infertility related to males with subnormal hypoosmotic swelling tests (HOST). The study would also determine if the copresence of poor morphology has any adverse effect on outcome. Methods: Clinical and viable pregnancy rates and implantation rates were evaluated in a second series of patients. The data were further stratified according to whether the semen specimen demonstrated morphology using strict criteria <4% normal vs ≥4%. Results: Clinical and viable pregnancy rates and implantation rates were 49.1, 45.3, and 23.4% for those with subnormal HOST scores and subnormal morphology vs 38.0, 34.3, and 22.5% for those with low HOST and strict morphology ≥4% (p = NS, chi-square analysis). Conclusions: In vitro fertilization with ICSI is an effective therapy for infertility related to subnormal HOST scores. Poor morphology does not adversely affect the outcome.

INCREASING SPERM CONCENTRATION TO ADJUST FOR SUBNORMAL SPERM MORPHOLOGY DID NOT ADVERSELY AFFECT IMPLANTATION AFTER EMBRYO TRANSFER

Some sperm specimens contribute to infertility not by impairing the fertilization process but by causing embryo implantation defects. One hypothesis is that a toxic factor attached to the sperm is transferred to the zona pellucida by the supernumerary sperm and then subsequently to the embryo membrane. One abnormality, as manifested by subnormal hypoosmotic swelling test (HOST) scores, causes these problems even with the small number of sperm that attach to the zona pellucida under normal physiologic conditions. This study evaluated whether the technique used to increase the oocyte insemination concentration of sperm to adjust for subnormal morphology values using strict criteria may allow a higher concentration of this purported toxic factor to attach to the zona pellucida, thus resulting in the dissimilitude of normal fertilization rate but low implantation rate. A comparison of the pregnancy and implantation rate of embryos formed by insemination of this adjusted sperm concentration of < or = 200,000 sperm vs. those inseminated with the normal concentration of 25,000 sperm failed to demonstrate any differences. Thus, the technique of increasing sperm concentration to adjust for low sperm morphology to improve fertilization rates does not seem to adversely affect implantation rates as long as the HOST scores are normal.Some sperm specimens contribute to infertility not by impairing the fertilization process but by causing embryo implantation defects. One hypothesis is that a toxic factor attached to the sperm is transferred to the zona pellucida by the supernumerary sperm and then subsequently to the embryo membrane. One abnormality, as manifested by subnormal hypoosmotic swelling test (HOST) scores, causes these problems even with the small number of sperm that attach to the zona pellucida under normal physiologic conditions. This study evaluated whether the technique used to increase the oocyte insemination concentration of sperm to adjust for subnormal morphology values using strict criteria may allow a higher concentration of this purported toxic factor to attach to the zona pellucida, thus resulting in the dissimilitude of normal fertilization rate but low implantation rate. A comparison of the pregnancy and implantation rate of embryos formed by insemination of this adjusted sperm concentration of £ 200,000 sperm vs. those inseminated with the normal concentration of 25,000 sperm failed to demonstrate any differences. Thus, the technique of increasing sperm concentration to adjust for low sperm morphology to improve fertilization rates does not seem to adversely affect implantation rates as long as the HOST scores are normal.

Relationship of Subnormal Semen Parameters and Subsequent Zona Pellucida Thinning Following in Vitro Fertilization

Infertility due to male factor has been associated with reduced implantation rates despite normal fertilization. The mechanism responsible for lower pregnancy rates is not known. One cause of failure to achieve pregnancy despite transfer of embryos is impairment of zona pellucida (ZP) thinning, which inhibits the embryo from hatching despite initial cell cleavage. This study was designed to evaluate whether there is an association between the ability of the ZP to thin, as measured by ZP thickness on day of transfer, and subnormal semen parameters. Significant differences in ZP thickness (p < 0.05, Kruskal-Wallis) were noted according to median concentration of sperm, total motile sperm, and motile density in that these values were the highest in the group of embryos with the thinnest zona pellucida and lowest in the group with the thickest zona pellucida. Thus, some factor may be missing from sperm from subnormal specimens that normally assists in zona thinning.

Absence of sperm with rapid motility is not detrimental to IVF outcome measures when ICSI is used.

The objective of the current study was to investigate the association between rapid motility of sperm and IVF outcome when ICSI is used for insemination of oocytes. The first IVF cycle of women up to age 42 were evaluated. Patients were classified into groups by the presence/absence of sperm with rapid motility (“A” sperm) in the specimen before and after sperm preparation. Group 1 had 0% A sperm prewash and 0% A postwash (n = 45); Group 2 had 0% A sperm prewash but some A sperm postwash (n = 47); Group 3 had A sperm both pre and postwash (n = 141). Statistical analysis demonstrated no difference in the fertilization, PRs, or implantation rates in the three groups. These data suggest that absence of sperm with rapid motility postseparation of sperm from seminal plasma is not detrimental to IVF outcome when ICSI is used for insemination.

PREGNANCY/IMPLANTATION RATES AS RELATED TO AGE FOLLOWING TRANSFER OF FROZEN EMBRYOS PRODUCED BY ICSI

A study has suggested that one drawback of ICSI is that if these embryos are cryopreserved they have lower implantation rates after thawing and transfer as compared to other frozen embryos derived from conventional oocyte insemination. Other studies have not shown such adverse effects on pregnancy rates following frozen embryo transfer (ET) of embryos formed by ICSI. The study presented here evaluated the largest number of frozen ET cycles of embryos following ICSI, which were compared to couples having frozen ET with embryos formed by conventional insemination. In women age 39 and younger, the clinical, viable, pregnancy rates and implantation rates were very similar. Similar rates were reached for the older group. These data convincingly demonstrate that fertilization by ICSI does not adversely effect the implanting capacity of frozen-thawed embryos.

Evaluation of sperm nuclear morphology in specimens with abnormal sperm chromatin structural assays.

Two recent tests have claimed to identify the subfertile male even when other semen parameters were normal: the sperm chromatin structure assay (SCSA) and abnormal sperm nuclear morphology using much higher magnification. The present study attempted to determine if having a high (> 30%) DNA fragmentation index (DFI), thus resulting in an abnormal SCSA test, is associated with a greater likelihood of sperm with abnormal nuclei. Four males with high DFI scores (57.6%, 65.4%, 31.0%, and 35.3%) had their nuclei evaluated by a complex microscope set-up that magnifies the sperm at least 6000 × . The corresponding % of normal nuclei was 0%, 20.0%, 23.7% and 40.0%. The mean and median % of normal nuclei was 20.9±16.43 and 21.8, respectively. More studies of similarly matched refractory in vitro fertilization cases, where males have normal DFI scores, are needed to determine if having a high DFI index is associated with a lower percentage of normal nuclei.