M. L. Check

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.

Detrimental Effects of Cryopreservation on the Structural and Functional Integrity of the Sperm Membrane

Many centers have been disappointed with the pregnancy rate following the insemination of cryopreserved-thawed sperm, despite the maintenance of an adequate motile density. The possibility exists that damage to the sperm membrane might occur despite preservation of other semen parameters. Simple measurements of structural integrity (viability) and functional integrity (hypoosmotic swelling test) were performed on thawed specimens. In each instance, both the viability and HOS scores were less than the critical 50% level. Specimens from three different commercial centers had very poor HOS and viability scores from two of the centers, and, though the scores were generally greater than or equal to 50% from the third center, this was achieved by eliminating 11 of 12 donors. Reducing the glycerol concentration from 12 to 7% and switching from Nunc vials to plastic embryo straws did not improve the poor sperm membrane tests. The possibility exists that if modification of the cryopreservation technique leads to improved HOS and viability scores, perhaps improved pregnancy results will be realized.

POOR HYPO-OSMOTIC SWELLING TEST RESULTS FROM CRYOPRESERVED SPERM DESPITE PRESERVATION OF SPERM MOTILITY

Cryopreservation thawing of sperm leads to decreased motile density. Most donor programs select for cryopreservation a male with a high initial motile density and if the post-thaw semen has a motile density over 10 x 10(6)/ml, the specimen is thought to represent a fertile specimen. Some recent data suggest that males with normal motile densities but subnormal hypo-osmotic swelling (HOS) tests may be infertile. A study was thus performed to see if males with an adequate motile density after cryopreservation may still demonstrate membrane damage as evidenced by decreased viability and a poor HOS test. The semen species from seven men with motile densities greater than or equal to 10 x 10(6)/ml after freeze-thawing were evaluated for HOS changes and viability. Despite preservation of normal motile density, all 7 men had HOS scores below 50% following cryopreservation (though all were significantly above this level pre-freeze). The mean viability and HOS scores prefreezing were 70 +/- 9.7 and 68.5 +/- 9.5, and post thaw they dropped to 33.7 +/- 6.9 and 32.8 +/- 6.2. These data suggest a mechanism for impaired fertility even with adequate motile density of a thawed specimen that had been cryopreserved.

The effect of leuprolide acetate in aiding induction of ovulation in hypergonadotropic hypogonadism: a case report

A 43-year-old woman with a history of 5 years of amenorrhea sought help in achieving a pregnancy. Her gonadotropins were found to be elevated and thus she was diagnosed as having ovarian failure. She was made to ovulate on many occasions by suppressing her gonadotropins first with estrogen, then stimulating her ovaries with hMG. However, she became refractory to this therapy and she was switched from estrogen to LA to suppress gonadotropins. The woman ovulated three times just with leuprolide therapy before any hMG was added. A possible hypothesis is that, on the way down to subnormal levels of LH and FSH, a critical level of gonadotropins was attained where they were still high enough to stimulate the follicles, but low enough to allow restoration of gonadotropin receptors, which previously had been down-regulated by the elevated gonadotropin levels.

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.

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.

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.

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.

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.

CUMULATIVE PROBABILITY OF PREGNANCY FOLLOWING IVF WITH ICSI AND FRESH OR FROZEN EMBRYO TRANSFER

The authors studied the cumulative probability of pregnancy for up to 4 consecutive embryo transfer (ET) cycles with ICSI performed for male factor. Transfers could be either fresh or frozen. The clinical pregnancy rate (PR) for the first 4 cycles were similar [44%(61/366); 31%(44/138); 45% (14/31); 44%(4/9)]. Delivery rates were also similar. There was a lower PR on the second retrieval vs. the first retrieval (47% vs. 29%), but this may be related to most of the second retrievals occurring in the second transfer cycle (67%,31/55); this may be explained by women who were poor responders and required another retrieval without a frozen ET. The majority of transfers in cycle 1 were fresh, whereas cycles 2-4 used primarily frozen-thawed embryos. These data should be helpful for patients requiring IVF with ICSI in deciding to continue with more IVF cycles or consider other options.