D. Katsoff

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.

The Value of Motile Density, Strict Morphology, and the Hypoosmotic Swelling Test in in Vitro Fertilization-Embryo Transfer

This study was conducted to evaluate the effect of a single abnormal semen parameter on subsequent implantation and pregnancy rates (PRs) following in vitro fertilization-embryo transfer (IVF-ET). The parameters evaluated were motile density (MD), strict normal morphology (SNM), and the hypoosmotic swelling (HOS) test. A total of 592 IVF cycles were evaluated. Patients were divided into four groups each with one abnormal semen parameter except for the control: group 1 (n = 509), control group: MD > or = 10 x 10(6)/mL, HOS > or = 50%, SNM > or = 4%; group 2 (n = 51): HOS and SNM normal, MD < 10 x 10(6)/mL; group 3 (n = 14): MD and SNM normal, HOS < 50%; group 4 (n = 18): MD and HOS normal, SNM < 4%. The implantation rate was 10.2% for the control group. The implantation rate was similar for the low MD (9.0%) and the low SNM (16.7%) groups. However, the low HOS group had a significantly lower implantation rate (0%). The clinical PRs are similar in the control group and low MD and SNM groups, but decreased in the low HOS group (21.5, 15.0, 30.8, and 0%, respectively). Ongoing PRs were also similar with the exception of the low HOS group (0%). This comparative study supports previous conclusions that the subnormal HOS test is the best semen parameter available that predicts poor PRs. It also suggests that some qualitative defect in the embryos may result from defective sperm membranes, resulting in an apparently normal appearance but physiologically defective embryo.

REEVALUATION OF THE CLINICAL IMPORTANCE OF EVALUATING SPERM MORPHOLOGY USING STRICT CRITERIA

Several studies suggest that sperm with h 4% normal morphology (NM) using strict criteria are subfertile and IVF with ICSI may be needed. However, not all studies agree on the clinical importance of the use of NM with strict criteria. One study of males with oligozoospermia found a lower pregnancy rate (PR) following intercourse with sperm with NM >14% compared to specimen with h 4%. The study presented herein evaluated the efficacy of intrauterine insemination (IUI) according to NM using strict criteria. The clinical PRs for first IUI cycles were 30% (28/91) for 0-4% normal forms, 26% (71/268) for range of 5-14%, and 20% (11/53) for >14%. This study corroborates previous data with intercourse only, suggesting that sperm with NM h 4% using strict criteria are not necessarily associated with lower fecundity.

Transfer of cryopreserved embryos improved pregnancy rates in patients with damage to the functional integrity of the sperm membrane as measured by the hypo-osmotic swelling test

OBJECTIVE To compare the pregnancy rates (PRs) after transfer of cryopreserved embryos in patients who have damage to the functional integrity of the sperm membrane as measured by the hypo-osmotic swelling test to those without this defect. DESIGN Prospective clinical study. SETTING University-associated IVF center. PATIENTS Fifty-four patients enrolled in a matched prospective study to evaluate the effects of low HOS scores (<50%) on PRs after IVF-ET were followed to determine the PR after transfer of cryopreserved embryos. MAIN OUTCOME MEASURE Clinical PRs and implantation rates. RESULTS Fourteen patients with low hypo-osmotic swelling test scores underwent 21 frozen ET cycles, achieved for clinical pregnancies for a PR per cycle of 19.0% and an implantation rate of 7.1%. Twelve patients with normal hypo-osmotic swelling test scores underwent 21 frozen ET cycles, achieved five preganancies for a clinical PR per cycle of 23.8% and an implantation rate of 9.3%. CONCLUSION Previous studies have demonstrated an adverse effect of low hypo-osmotic swelling test scores on PRs after IVF-ET despite normal fertilization. This adverse effect was not found in the transfer of cryopreserved embryos from males with hypo-osmotic swelling test scores. Further investigation is required to determine how cryopreservation improves the chances of implantation of these embryos.

Evidence that oligoasthenozoospermia may be an etiologic factor for spontaneous abortion after in vitro fertilization-embryo transfer

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.

Two methods of achieving pregnancies despite subnormal hypo-osmotic swelling test scores

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.

Chymotrypsin-galactose treatment of sperm with antisperm antibodies results in improved pregnancy rates following in vitro fertilization.

PROBLEM: To determine if chymotrypsin‐galactose (CG) treatment of sperm bound with antisperm antibodies (ASA) improves pregnancy rates (PRs) following in vitro fertilization (IVF).

The Frequency of Antisperm Antibodies in the Cervical Mucus of Women With Poor Postcoital Tests and Their Effect on Pregnancy Rates

PROBLEM: To determine the impact of the presence of antisperm antibodies (ASAs) in the cervical mucus of female partners in couples with unexplained poor postcoital tests (PCT). Furthermore, the efficacy of intrauterine insemination (IUI) in these same patients was determined by pregnancy rates (PRs).

PROGNOSIS FOR SPERM FERTILIZABILITY: ANALYSIS OF DIFFERENT VARIABLES IN MEN

An overview of various sperm tests is presented. The standard semen analysis obtained by most clinicians evaluating infertility usually consists of sperm concentration, percent motility, quality of motility, and sperm morphology. Unfortunately, unless the motile density is extremely low, the count and motility are not good prognosticators of fertility potential. Values above the norm for normal fertile couples unfortunately cannot reliably predict normal fertility potential. It is important to find sperm tests that are easy to perform, are relatively inexpensive, and provide an accurate prognosis. Strict morphology was hoped to be such a tool with initial optimism that it was far superior to standard morphology. Unfortunately, this test also failed to be the ideal inexpensive prognostic test after further evaluation. One test that is inexpensive and highly correlates with fertilizability is the presence of antisperm antibodies since their presence frequently does not alter count, motility, or morphology. This test should be performed as part of the routine semen analysis. Other tests highly correlate with the achievement of pregnancy and are simple and inexpensive to perform, but, interestingly, do not correlate with fertilizability. These include the hypoosmotic swelling test (HOST) and the sperm stress test. Abnormalities in these tests imply a different abnormality of sperm that leads to conception failure and that is the transfer of a toxic factor from the sperm to oocyte to embryo that prevents the embryo from implanting. Certainly, the simple, inexpensive HOST should be performed routinely. Other tests of sperm function, e.g., sperm penetration assay, sperm-zona pellucida binding assay, and acrosome reaction, have their definite place in the evaluation of the infertile male. However, because they are expensive and difficulty to perform they lend themselves to certain specific circumstances but not to routine testing.

Evidence that sperm with low hypoosmotic swelling scores cause embryo implantation defects.

A previous prospective study using matched samples found that sperm with low hypoosmotic swelling (HOS) scores had no adverse effect on fertilization rates but markedly reduced pregnancy and implantation rates. The present study attempted to corroborate or refute the aforementioned study by comparing pregnancy rates in donor-recipient pairs using shared oocytes where the sperm of one of the two males had low HOS scores. The results found no pregnancies from the sperm with low HOS scores versus a 41% live delivered rate for those with normal scores. However, fertilization rates were not affected. This retrospective study thus confirms that sperm with low HOS scores cause implantation defects of the embryos that are formed without affecting fertilization rate, embryo cleavage rate, or embryo quality.A previous prospective study using matched samples found that sperm with low hypoosmotic swelling (HOS) scores had no adverse effect on fertilization rates but markedly reduced pregnancy and implantation rates. The present study attempted to corroborate or refute the aforementioned study by comparing pregnancy rates in donor-recipient pairs using shared oocytes where the sperm of one of the two males had low HOS scores. The results found no pregnancies from the sperm with low HOS scores versus a 41% live delivered rate for those with normal scores. However, fertilization rates were not affected. This retrospective study thus confirms that sperm with low HOS scores cause implantation defects of the embryos that are formed without affecting fertilization rate, embryo cleavage rate, or embryo quality.