The correlation of the degree of abnormal sperm morphology using strict criteria and pregnancy rates following intrauterine insemination (IUI).

OBJECTIVE: To determine the effect of extremely low sperm morphology on pregnancy rates following intrauterine insemination (IUI) where all other semen parameters were normal. MATERIALS AND METHODS: Retrospective review of all IUI cycles over a two-year period on infertile women age ≤ 35 where all parameters, but morphology had to be normal. The data were evaluated according to seven levels of percentage of normal morphology (NM): 0, 1, 2, 3, 4, 5, and ≥ 6%. RESULTS: The percent live delivery was 9.5, 16.7, 8.8, 16.1, 11.4, 12.3, and 10.9%. CONCLUSIONS: Morphology of 0% or 1% did not seem to impair pregnancy rates following IUI. More studies are needed but should include determining the confounding effect of the type of morphologic abnormality.

Correlation of ImmunoBead® and ImmunoSphere™ Immunoglobulin G (IGG) tests on detecting antisperm antibody (ASA) on sperm.

PURPOSE: To determine the correlation with detection of antibody on sperm by a new ImmunoSphere™ Immunoglobulin test vs. ImmunoBeads®. MATERIALS AND METHODS: A sampling of sperm tested for antisperm antibody (ASA) tested by direct Immunobead? assay with levels varying from zero to 100% were compared to the percentage of sperm positive for ASA by a new test using immunospheres. RESULTS: The correlation was not perfect but, in general, there was good correlation. CONCLUSION: Now that the manufacturer is curtailing the manufacture of immunobeads, it is comforting to see a good correlation with immunospheres.

Failed fertilization with conventional oocyte insemination can be overcome with the ability of ICSI according to binding or failing to bind to the zona pellucida.

PURPOSE: To determine the frequency of failed fertilization with conventional oocyte insemination and to determine the ability of intracytoplasmic sperm injection (ICSI) to overcome the failed fertilization according to binding or failing to bind to the zona pellucida. MATERIALS AND METHODS: Retrospective review of 12,448 in vitro fertilization (IVF) cycle to identify cycles where failed fertilization occurred following conventional oocyte insemination with seemingly normal sperm. A number of three oocytes retrieved was required. RESULTS: There were only 12 cases of failed fertilization (0.1%). Six were related to failure of any or few sperm attaching to the zona pellucida These six had high fertilization rates with ICSI. Six had normal attachment and five attempted another cycle, this time with ICSI. Only 60% had good fertilization. CONCLUSIONS: When there is failed fertilization with normal sperm oocyte binding following conventional oocyte insemination, ICSI may still be effective in 60% of the cases, but it would be probably recommended to combine ICSI with artificial oocyte activation by calcium ionophore.

Effect of poor motility on pregnancy outcome following intracytoplasmic sperm injection in couples whose male partners have subnormal hypo-osmotic swelling test scores.

PURPOSE: To determine the confounding effect, if any, of poor motility of sperm that are already compromised by an abnormal hypo-osmotic swelling (HOS) test on pregnancy outcome following in vitro fertilization-embryo transfer (IVF-ET) and intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: Clinical and live-delivered pregnancy and implantation rates were retrospectively evaluated in first cycles of couples undergoing IVF-ET with ICSI where the HOS test was < 50% according to deciles of subnormal percentage motility (< 50%) and compared to those with normal motility > or = 50%. RESULTS: The combination of very poor motility and low HOS test scores did diminish pregnancy rates following IVF with ICSI. CONCLUSIONS: The only part of fertilization of the oocyte that ICSI does not overcome is phase 2 of oocyte activation. Based on these data, the combination of very low percentage motility and low HOS test scores do not adversely affect pregnancy outcome following IVF with ICSI.

Isolating sperm by selecting those with normal nuclear morphology prior to intracytoplasmic sperm injection (ICSI) does not provide better pregnancy rates compared to conventional ICSI in women with repeated conception failure with in vitro fertilization.

PURPOSE: To determine if isolation of sperm by nuclear characteristics using high magnification offers any advantage over the normal morphologic methods when performing intracytoplasmic sperm injection (ICSI) in refractory cases in which the male partner had an abnormal DNA fragmentation index. MATERIALS AND METHODS: Women aged < or = 39 with failure to have a successful conception after three consecutive embryo transfers whose male partner had a DNA fragmentation index > 30% were randomly assigned to isolation of sperm for ICSI by a new high magnification procedure to evaluate nuclear morphology and the usual method with normal magnification where nuclear characteristics were not seen. Women 40-43 were not randomized and were given the option after hearing pros and cons. RESULTS: Overall the live delivered pregnancy rates were similar in the high vs normal magnification groups (33.3% vs 36.3%). CONCLUSIONS: Isolation of sperm with normal nuclei with high magnification does not offer any advantage over conventional IVF for refractory cases where the male partner has a high DNA fragmentation index.

Intrauterine insemination (IUI) does not improve pregnancy rates in infertile couples where semen parameters are normal and postcoital tests are adequate.

PURPOSE: To determine if intrauterine insemination (IUI) improves pregnancy rates in couples with a correctable ovulatory defect but a male partner with an apparent normal semen analysis and a normal postcoital test. MATERIALS AND METHODS: A prospective evaluation of clinical live delivered pregnancy rates following the first cycle where follicular maturation was demonstrated naturally or with a follicle maturing drug. The couples were given the option of IUI. RESULTS: The live delivered pregnancy rates per IUI cycle were similar with intercourse only vs addition of IUI (18.7% vs 21.4%). CONCLUSIONS: There is no evidence to support the notion that IUI improves pregnancy rates in circumstances where the semen analysis and postcoital tests are normal.

Low hypo-osmotic swelling tests correlate with low percent motility and age of the male.

PURPOSE: To determine if sperm motility and hypo-osmotic swelling (HOS) test scores are associated. Furthermore the study would determine if the chance of having a subnormal HOS test increases as motility levels decrease. Finally the study would determine if age, motility, and HOS test scores are independent factors or if they interact. MATERIALS AND METHODS: A retrospective analysis of males of all ages with a normal sperm concentration of > 20 x 10(6)/ml is presented. Males were evaluated separately according to age (< 40 vs > or = 40 years) for percent progressive motility and HOS test scores. The percent motility was assessed according to percentage in deciles. RESULTS: A significantly higher percentage of males with low motility have low (< 50%) HOS test scores irrespective of age. The odds ratio of males < 40 years having an abnormal HOS test score is 6.73 times higher and is 8.23 times higher for males > or = 40 years. As age increases, there is a significantly larger proportion of males with abnormal HOS test scores (6% to 13%). CONCLUSIONS: Factors that cause an abnormality in the functional integrity of the sperm membrane, as evidenced by a low HOS test score, can also have a negative effect on motility.

Low hypoosmotic swelling test scores correlate better with lower percent motility than any other abnormal semen parameters.

PURPOSE: To determine if any single abnormal semen parameter is associated with low hypoosmotic swelling (HOS) test scores. METHODS: A retrospective review evaluating males with single sperm defects of sperm concentration, % progressive motility, morphology using strict criteria, and antisperm antibodies. The percentage of these males with HOS test scores < 50% was then determined. RESULTS: By far the abnormal semen parameter most associated with a subnormal HOS test was poor motility. CONCLUSIONS: Though we believe that the simple inexpensive HOS test should be performed routinely when performing semen analysis, it is especially important to evaluate in males with poor motility since simple intrauterine insemination will not allow pregnancies.

Frequency of subnormal hypoosmotic swelling tests increase with advancing age of the male.

PURPOSE: To determine if there is an increased frequency of abnormal hypoosmotic swelling (HOS) tests when testing semen in males of advanced reproductive age. METHODS: Ten-year retrospective review according to six age groups (< or = 29.9, 30-34.9, 35-39.9, 40-44.9, 45.0-49.9, and > or = 50). RESULTS: Compared to males < 35 years old, the frequency of HOS scores < 50% doubles in males 45-49.9 and quadruples in males > or = 50. CONCLUSIONS: Males with low HOS scores despite having no problem with fertilization of the oocytes rarely achieve a pregnancy because of embryo implantation defects unless intracytoplasmic sperm injection (ICSI) is performed. Thus at least one abnormality seen in sperm of males of advanced reproductive age is correctable by performing in vitro fertilization with ICSI.

The majority of males with subnormal hypoosmotic test scores have normal vitality.

PURPOSE: To determine if males with low hypoosmotic swelling (HOS) test scores may have normal vitality tests. METHODS: Retrospective nine-year review of initial semen analyses evaluating vitality and HOS tests. RESULTS: Only 12.5% (45/361) of males with low HOS test scores have low vitality. CONCLUSIONS: WHO seems to treat vitality and HOS as equal tests. We disagree and find that structural defects of the sperm membrane are much less common than functional impairment of the sperm membrane. Since a male with an HOS test score < 50% will rarely achieve a pregnancy with intercourse, intrauterine insemination, or IVF with conventional insemination it is important to check for the HOS test not viability because the HOS test can be easily corrected with ICSI.

A case whose outcome is consistent with the possibility that if slow embryo cleavage is related to a male factor the prognosis is far greater than if it was related to an egg factor.

PURPOSE: To determine if the male partner's sperm can be the cause of embryos with slow cleavage. METHODS: Retrospective evaluation of shared donor oocyte pairs where two women shared one pool of oocytes from an oocyte donor. RESULTS: Only one woman formed embryos that were all < 6 blastomeres in 376 paired cycles (total 752). With one previous IVF cycle where she formed only two embryos (5-cell and 4-cell) this woman had in five embryos formed all < 6-cells and four of five only 4-cells on day 3. In contrast, the woman who was donating half of the oocytes but had her half fertilized by her own male partner's sperm had only one of three with < 6-cells. CONCLUSIONS: This study suggests that rarely the sperm may be the reason for slow cleaving embryos.

Comparison of the efficacy of treating sperm with low hypoosmotic swelling test scores with chymotrypsin followed by intrauterine insemination vs in vitro fertilization with intracytoplasmic sperm injection.

PURPOSE: To compare the efficacy of two treatments for sperm with low hypoosmotic swelling (HOS) test scores - intrauterine insemination (IUI) with sperm pretreated with the protein digestive enzyme chymotrypsin versus in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI). METHODS: The choice of patient therapy was optional. The pregnancy rates following two IUI cycles vs one IVF cycle with ICSI were then compared. The data were further stratified and compared according to the severity of the HOS score defect. RESULTS: The more severe the HOS test defect the less likely for chymotrypsin therapy to work whereas the severity did not affect IVF with ICSI success. The use of IVF with ICSI was much more effective than IUI with chymotrypsin treatment. CONCLUSIONS: Though IVF with ICSI is much more effective, IUI is much less expensive. Couples should be presented with these data and be allowed to make their own choice considering risks and expense versus efficacy and speed of success.

About 13% of women may have the wrong method of oocyte insemination when undergoing in vitro fertilization by failure to evaluate the abnormal hypo-osmotic swelling test score.

PURPOSE: To determine the percentage of males with a low hypoosmotic swelling (HOS) test score in couples having in vitro fertilization-embryo transfer (IVF-ET) where the male partner had normal motile densities and no antisperm antibodies. METHODS: The results were also analyzed according to the percentage of HOS scores < 50% when morphology using strict criteria was < or = 4% or > 4%. A retrospective review was performed. RESULTS: There were 250 subnormal HOS scores out of 1993 otherwise normal semen specimens. CONCLUSIONS: 12.5% of couples would have had conventional oocyte inseminations rather than ICSI if the HOS test had not been not performed (it is rarely performed by other IVF centers). Without ICSI expected live delivered pregnancy rates would be close to zero for males with low HOS tests < 50%. Intracytoplasmic sperm injection allows pregnancy rates almost as good as completely normal sperm.

Effect of fertilization by intracytoplasmic sperm injection versus conventional insemination on embryo cleavage rates.

PURPOSE: To determine if fertilization by conventional oocyte insemination vs intracytoplasmic sperm injection (ICSI) causes any difference in the maximum number of blastomeres of fresh or frozen thawed embryos transferred. METHODS: Retrospective evaluation of all in vitro fertilization (IVF) cycles over a 10-year period in cycles having a 2 embryos transferred where the semen analysis was normal except for strict morphology which was allowed to be 2-5% normal. The percentage of the maximum number of blastomeres in any transfers was compared according to the method of insemination. RESULTS: There were no differences in the maximum blastomere numbers in cycles where there was conventional insemination vs ICSI. CONCLUSIONS: Though higher pregnancy rates have been found following the transfer of embryos derived from conventional oocyte insemination vs ICSI, and higher pregnancy rates were found following single embryo day 3 transfers with embryos with more blastomeres, the beneficial effect of conventional insemination does not seem to be related to forming embryos with more rapid cleavage.

Pretreatment of sperm with low hypo-osmotic swelling tests with chymotrypsin prior to intrauterine insemination (IUI) and avoidance of unprotectected intercourse results in pregnancy rates comparable to IUI for other male factor problems.

PURPOSE: To carry out a retrospectively performed matched controlled study to determine the efficacy of pretreatment of sperm having low hypo-osmotic swelling (HOS) test scores with chymotrypsin galactose prior to intrauterine insemination (IUI) compared to IUI for other types of male factor problems. The women with male partners with low HOS scores were advised not to have unprotected intercourse. METHODS: All cycles having IUI with chymotrypsin treated sperm for low HOS scores were matched with the very next woman having IUI for sperm with other male factor problems but with normal HOS scores. RESULTS: There was a significantly higher clinical pregnancy rate with chymotrypsin treated sperm (32.3% per IUI) vs. 21.9% for other male factor cases. The live birth rate per IUI cycle was not significantly different (21.2% vs. 15.4%). CONCLUSIONS: These results now show that pretreatment of sperm with low HOS scores allows very good pregnancy rates following IUI as long as the couple is cautioned about unprotected intercourse. These data support the concept that sperm with low HOS test scores impair fertility by transferring a toxic factor from the sperm to the zona pellucida to the embryo membrane which impairs the embryos from implanting.

Fertilization by intracytoplasmic sperm injection with sperm with subnormal morphology using strict criteria results in lower live delivered pregnancy rates following frozen embryo transfer rather than eggs fertilized conventionally.

PURPOSE: To determine if fertilization by intracytoplasmic sperm injection (ICSI) lowers pregnancy rates following frozen embryo transfer compared to conventional insemination similar to findings with fresh embryo transfer. METHODS: Clinical and live delivered pregnancy and implantation rates were compared according to whether the eggs were fertilized by conventional oocyte insemination vs ICSI over a 10-year period in women whose husbands had normal semen parameters except for having normal strict morphology between 2-5%. RESULTS: The clinical and live delivered pregnancy rates were 40.9% and 31.9, respectively, with ICSI vs. 44.2% and 38.3% for women having conventional insemination. The difference in live delivered pregnancy rates approached statistical significance. CONCLUSIONS: Choosing ICSI for subnormal morphology may not only possibly lower the chance of successful pregnancy following fresh embryo transfer but possibly also following frozen embryo transfer.

Conventional oocyte insemination may result in a better pregnancy outcome than intracytoplasmic sperm injection (ICSI) for unexplained infertility.

PURPOSE: To determine in cases of unexplained infertility whether conventional oocyte insemination vs. intracytoplasmic sperm injection results in differences in fertilization rates, frequency of failed fertilization, clinical and live delivered pregnancy rates, and implantation rates. METHODS: Retrospective evaluation of these parameters in couples undergoing in vitro fertilization embryo transfer (IVF-ET) (minimum 2 embryos) in women with unexplained infertility over a 7-year period. RESULTS: There was a significantly higher fertilization rate (p < .001) with ICSI vs. conventional insemination (73.7% vs. 63.7%). However of greater clinical importance, the clinical and live delivered pregnancy rates were significantly higher with conventional insemination (52.7% and 46.2%) than with ICSI 33.6% and 29.0%. The implantation rates were also significantly higher with conventional oocyte insemination (24.9% vs. 17.8%). Failed fertilization was low in both groups. CONCLUSION: The process of ICSI, whether it involves possible subtle oocyte damage by the procedure or the andrologist not choosing the ideal sperm, may lead to embryos that are less hearty despite their normal appearance.

Miscarriage in the first trimester according to the presence or absence of the progesterone-induced blocking factor at three to five weeks from conception in progesterone supplemented women.

PURPOSE: To determine if the failure to detect the immonomodulatory protein progesterone induced blocking factor (PIBF) at three to five weeks of seemingly normal pregnancies in women supplemented by extra progesterone is associated with a higher miscarriage rate. METHODS: Progesterone-induced blocking factor expression by lymphocytes was measured by an immunocytochemistry technique. The serum beta human chorionic gonadotropin (hCG) and/or ultrasound were also deemed appropriate so that by these criteria there was no evidence of a poor pregnancy. The minimum progesterone dosage was 200 mg twice daily vaginal suppositories. RESULTS: Progesterone-induced blocking factor was detected in 17/39 (43.5%) of pregnant patients at this early time. There were three miscarriages by 12 weeks in this group (17.6%). The miscarriage rate was 6/21 (28.5%) in those where it was not detected. CONCLUSIONS: There was insufficient power to show significance. However there seems to be a trend for higher rates of miscarriage when PIBF is absent so these preliminary data encourage continuation of the study.

Reevaluation of the clinical importance of evaluating sperm morphology using strict criteria.

Several studies suggest that sperm with < or =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 < or = 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 < or =4%, using strict criteria are not necessarily associated with lower fecundity.

Do antisperm antibodies cause functional impairment of the sperm membrane as manifested by a low hypoosmotic swelling test score?

Low hypoosmotic swelling (HOS) test scores were found to be associated with lower pregnancy rates. The mechanism seems to be related not so much to impaired fertilization but to inhibition of implantation. The defect may be present in males with normal or subnormal semen specimens. However, anecdotal experience suggested that the subset of males with antisperm antibodies (ASAs) have a higher frequency of low HOS scores. The possibility exists that ASAs may impair the functional integrity of the sperm membrane. The study presented herein, artificially added ASAs to sperm to see if this could lower the HOS score. The study would also determine if chymotrypsin, a protein digestive enzyme, could improve HOS scores, if, in fact, they were lowered by the addition of ASAs. The results did not show a reduction in the HOS scores following the addition of ASAs. Thus, it would appear that there is no cause and effect with the simultaneous presence of low HOS scores and ASAs. Possibly, however, longer exposure or a higher concentration of antibodies is needed to lower HOS scores.