Effect of sperm morphology and motile sperm count on outcome of intrauterine insemination in oligozoospermia and/or asthenozoospermia

Eighty-six couples with long-standing infertility and poor postcoital test, due to oligozoospermia and/or asthenozoospermia (68 cases) or mucus hostility (18 cases), were treated by 411 intrauterine inseminations (IUI) with motile sperm suspensions from the husband's semen. The pregnancy rate per couple in the group with abnormal semen was lower than in the group with mucus hostility (22% versus 38.9%). Influence of seminal and other parameters on outcome of IUI was assessed by discriminant analysis, and a significant correlation with pregnancy rate was found for motile sperm count and sperm morphology. Teratozoospermia (normal morphology less than 50%) affected the outcome of IUI both when associated with moderate oligozoospermia and/or asthenozoospermia (motile sperm count greater than or equal to 5 X 10(6)/mL) (success rate per couple: 11.1%), and, even more, when associated with severe oligozoospermia and/or asthenozoospermia (motile sperm count less than 5 X 10(6)/mL), where no pregnancy was achieved. In the absence of teratozoospermia, the success rate per couple both in severe and in moderate oligozoospermia and/or asthenozoospermia had similar results (33.3% versus 35.7%). In conclusion, the absence of teratozoospermia appears to be an effective criterion for selecting couples with infertility due to oligozoospermia and/or asthenozoospermia who may benefit from IUI.     

Sperm washing and intrauterine insemination for cervical factor, oligospermia, immunologic infertility and unexplained infertility

The cumulative pregnancy rate was evaluated for 56 couples undergoing 227 intrauterine inseminations (IUIs) after sperm washing. The indications for IUI were cervical factor, oligospermia, immunologic infertility and unexplained infertility. The overall pregnancy rate was 21.4%, with a 0.289 cumulative probability of conception after six cycles. Within each category the pregnancy rates were 25% for cervical factor, 60% for women with antisperm antibodies, 20% for men with antisperm antibodies and 7% for oligospermia.     

Evaluation of the antisperm antibodies in infertile couples afflicted with a cervical factor

OBJECTIVES: The purpose of this study was to evaluate methods used for antisperm antibodies detection in infertility. METHODS: The studied cohort comprised 38 infertile couples with a distinct cervical factor. Presence of antisperm antibodies and their levels in circulation were evaluated in sera samples of both partners and also in the cervical mucus and semen with the Latex Agglutination test. Western Blotting was applied as an additional method in antibody detection. We also assessed: the number of sexual partners, potentially allergizing sexual behaviour and other potentially sensitising factors. RESULTS: The positive antisperm antibodies were detected merely twice and only in one case there was evidence of insemination-impeding antisperm humoral response. The Western Blotting method enabled us to obtain a reaction to a range of sperm proteins which reacted with antibodies both in serum and in seminal plasma. CONCLUSIONS: Determination of infertility on immunological grounds on the basis of a single determinant on sperm presents little diagnostic value. In our view, the combination of patient's clinical status with immune-system response to a spectrum of sperm antigens provides means of infertility evaluation. We propose Western Blotting as an useful technique for detection of antisperm antibodies.     

A simple method of screening for antisperm antibodies in the human male. Detection of spermatozoal surface IgG with the direct mixed antiglobulin reaction carried out on untreated fresh human semen.

A simple and rapid test for the detection of antisperm antibodies of the IgG class on freely swimming spermatozoa in fresh human semen is described. The test is based on the formation of motile mixed agglutinates between erythrocytes sensitized with incomplete anti-Rh-antibodies and freely swimming spermatozoa with surface antisperm antibodies, after mixing both cell types together with anti-IgG antiserum. Agglutination of the red blood cells serves as an internal control. The test can be applied on ejaculates with spermatozoa concentrations down to one million per ml, provided the motility is sufficient. The percentage of motile spermatozoa found to be coated with antisperm antibodies of the IgG class, and the extent of the coating, proved to be correlated with the agglutination titer of circulating antisperm antibodies and with the inhibition of sperm penetration into cervical mucus. The test can be used as a screening for the presence of antisperm autoantibodies in serum and semen.     

Analysis of factors influencing pregnancy rates in homologous intrauterine insemination

OBJECTIVE: To identify predictors of pregnancy rate (PR) among women undergoing homologous IUI. DESIGN: Cross-sectional analysis of IUI cycles carried out from January 2000 to September 2002. SETTING: Private infertility center in Alicante, Spain. PATIENT(S): Four hundred seventy women undergoing 1,010 cycles of IUI. INTERVENTION(S): Single IUI with ovarian stimulation using hMG. MAIN OUTCOME MEASURE(S): Preovulatory follicles (>15 mm), motile spermatozoa count, type and duration of infertility, female age, insemination timing, and cycle number. RESULT(S): Overall PR per cycle and multiple pregnancy and miscarriage rates were 9.2%, 8.6%, and 11.8%, respectively. Three significant predictors of pregnancy were identified by multiple logistic regression analysis: preovulatory follicles, spermatozoa count, and infertility duration. Interuterine insemination with three follicles almost tripled the PR with respect to only one, odds ratio (OR) = 2.89 (95% confidence interval [CI], 1.54-5.41). Compared with insemination with a motile sperm count >30 x, 20.1-30, 10.1-20, 5.1-10, and < or =5 x10(6), insemination progressively decreased the PR, from 15.3% in the highest category to 3.6% in the lowest (OR lowest/highest = 0.20 [95% CI: 0.09-0.45]), with a statistically significant dose-response trend. Infertility duration > or =3 years was marginally associated with a lower PR, OR = 0.65 (95% CI, 0.40-1.04). Overall, female age was not a significant predictor of pregnancy, and although PR slightly decreased beyond two IUI cycles and when a single IUI was performed 36-40 hours after hCG administration, results were not statistically significant. CONCLUSION(S): Homologous IUI achieves the best results with two or three induced follicles, a high motile spermatozoa count, and infertility duration <3 years, irrespective of female age and fertility history.     

The impact of the total motile sperm count on the success of intrauterine insemination with husband's spermatozoa

Purpose: The purpose of this study was to evaluate the relationship between the total motile sperm count and the success of IUI treatment cycles with postwashed husband spermatozoa in couples with infertility in a large patient population. Patients: When 939 couples underwent 1375 cycles of IUI with varying etiologies of infertility which included male factor, endometriosis, tubal factor, ovulatory dysfunction, uterine factor, cervical factor, and unexplained infertility, the results were 207 pregnancies. Results: The overall pregnancy rate per cycle was 15.1% (207/1375). The total motile sperm count were significantly increased in the pregnant group than the nonpregnant group (38.7×10⁶ versus 28.6 × 10⁶;P<0.001). There was a trend toward an increased success rate with increased total motile sperm count. Significance was reached when the total motile sperm count exceeded 5×10⁶. Life table analysis was performed and the curve representing a cumulative chance of pregnancy calculated from our data reached 72%. Conclusions: Our findings suggest that a final postwashed total motile sperm count used for IUI may be considered predictive of the success for pregnancy and allow couples to be informed of the chances of success.     

Isolated teratozoospermia and intrauterine insemination

OBJECTIVE: This study tests the hypothesis that IUI treatment in cases with isolated teratozoospermia (<10% normal forms using strict criteria, normal motility and normal count), results in a lower cumulative live birth rate compared to cases with normozoospermia. DESIGN: A retrospective cohort study. SETTING: An academic fertility center. PATIENT(S): Eight hundred seventy-two IUI cycles in 440 couples were analyzed. INTERVENTION(S): Couples (n = 440) were classified in three groups: normozoospermia (n = 213), isolated teratozoospermia (n = 104), and male factor infertility (n = 123). MAIN OUTCOME MEASURE(S): Live birth rate per cycle and cumulative live birth rate (CLBR). RESULT(S): The three groups were similar with regard to female age, female infertility factors, and ovarian response after hormonal stimulation. The overall CLBR after four cycles was 41.5%, and was significantly increased in the normozoospermic group (52.8%) when compared to the isolated teratozoospermia group (33.4%) and the male factor infertility group (31.4%). CONCLUSION(S): This study documents for the first time that the CLBR after four IUI cycles is significantly and similarly reduced in couples with isolated teratozoospermia as in couples with other sperm defects, when compared to couples with normozoospermia. As with couples with male factor infertility, couples with isolated teratozoospermia should be counseled about other treatment options such as IVF, as the CLBR after three IVF cycles is 70%-80% in our program.     

Timed intercourse after intrauterine insemination for treatment of infertility

Objective: To compare the pregnancy rates, between intrauterine insemination (IUI) followed by timed intercourse and IUI only for treatment of the infertile couples. Study design: A prospective study of two different protocols of intrauterine insemination in two hundred and one infertile couples with a normal spermiogram was carried out. Of these, 101 couples were treated with IUI alone and 100 couples had both IUI and timed intercourse within a 12-18 h period. The pregnancy rates were compared between groups. Results: The characteristics of the two groups were similar in terms of the mean age, as well as the duration and causes of infertility. The cycle characteristics following follicular stimulation were also similar between two groups. The pregnancy rate per cycle increased with increasing numbers of total motile sperm per insemination in the IUI alone group (P=0.045). Timed intercourse increased pregnancy rate in patients with lower motile sperm number (<40×10⁶) (27.7% versus 10.5%, P=0.023), but not in patients with higher sperm number (≥40×10⁶) (25.7% versus 22.7%, P=0.671). Conclusions: In IUI with low number of motile sperm inseminated, timed intercourse significantly increases the pregnancy rates over IUI alone in infertile couples with a normal sperminogram. This alternative treatment appears to be a practical, simple, and inexpensive addition that improves the pregnancy rate in patients receiving ovulation induction and intrauterine insemination program.     

Effect of the total motile sperm count on the efficacy and cost-effectiveness of intrauterine insemination and in vitro fertilization

OBJECTIVE: To determine prognostic factors for achieving a pregnancy with intrauterine insemination (IUI) and IVF. To compare the effectiveness and cost-effectiveness of IUI and IVF based on semen analysis results. DESIGN: Retrospective cohort study. SETTING: Academic university hospital-based infertility center. PATIENT(S): One thousand thirty-nine infertile couples undergoing 3,479 IUI cycles. Four hundred twenty-four infertile couples undergoing 551 IVF cycles.Intervention(s): IUI and IVF treatment. MAIN OUTCOME MEASURE(S): Multiple logistic regression analysis was used to assess the significance of prognostic factors including a woman's age, gravidity, duration of infertility, diagnoses, use of ovulation induction, and sperm parameters for predicting the outcomes of clinical pregnancy and live birth rate after the first cycle of IUI and IVF. The relative effectiveness and cost-effectiveness of these treatments were then determined based on sperm count results. RESULT(S): Female age, gravidity, and use of ovulation induction were all independent factors in predicting pregnancy after IUI. The average total motile sperm count in the ejaculate was also an important factor, with a threshold value of 10 million. For IVF, only female age was an important predictor for both clinical and ongoing pregnancy. When the average total motile sperm count was under 10 million, IVF with ICSI was more cost-effective than IUI in our clinic. CONCLUSION(S): An average total motile sperm count of 10 million may be a useful threshold value for decisions about treating a couple with IUI or IVF.     

Evaluation of antisperm antibodies in infertile couples with immunobead test: prevalence and prognostic value

We know that antisperm antibodies can cause infertility. We studied the prevalence of the immune response against spermatozoa in infertile couples using immunobead test. 16.2% of the men were autoimmune and 7.3% of the women isoimmune. Both partners were immune in 1.6% of the couples. We also studied the degree of impairment of sperm penetration into cervical mucus in couples in which one of the partners exhibited immunity and we found that generally it correlates with the proportion of sperm exhibiting surface-bound immunoglobulins. In some cases the sperm penetration into cervical mucus was normal in spite of immunization. So other mechanisms of interference should be explored. We found a significant difference (p less than 0.02) in the conception rate between immune and non immune couples (19.3% vs 42%). The pregnancy outcome of immune couples was favorable only in 50% of the cases.     

Autoimmunity to spermatozoa: effect on sperm penetration of cervical mucus as reflected by postcoital testing

In couples with abnormal postcoital tests, where husbands exhibited autoimmunity to spermatozoa, the degree of impairment of sperm penetration into cervical mucus correlated with the proportion of sperm in ejaculates exhibiting surface-bound immunoglobulins. Residual sperm-directed antibodies detected within seminal fluid were not representative of the cell-bound immunoglobulins present on the sperm surfaces. When all sperm were antibody-bound, spermatozoa were rarely seen in cervical mucus. Conversely, the number of motile sperm seen at postcoital testing was normal, that is, no different from that of antibody-negative couples, when less than 50% of sperm were antibody-bound in the ejaculate. In this group, other causes of infertility should be explored. The extent of autoimmunity to spermatozoa as reflected in the proportion of sperm exhibiting immunobead binding, then, provides guidelines for treatment of these men.     

Percutaneous vasal sperm aspiration and intrauterine insemination in the treatment of obstructive azoospermia

Objective: To treat obstructive azoospermia by using sperm recovered from percutaneous vasal sperm aspiration in IUI.

Design: Clinical study.

Setting: Institutional clinic in Jinan.

Patient(s): Six men with obstructive azoospermia, three of whom were treated with percutaneous vasal sperm aspiration and IUI; sperm recovered from this procedure were used for IUIs.

Intervention(s): Spermatozoa used for intrauterine injection were retrieved by percutaneous vasal sperm aspiration and incubated at 37°C for 40 to 60 minutes.

Main Outcome Measure(s): Normal pregnancy.

Result(s): Intrauterine insemination was performed in three patients for one or two cycles, with motile spermatozoa. There was one successful term delivery.

Conclusion(s): Percutaneous vasal sperm aspiration can be used successfully to recover sperm in men with obstructive azoospermia for use in IUI. The technique is simple and less traumatic than an open surgical procedure.     

A prospective trial of intrauterine insemination of motile spermatozoa versus timed intercourse

STUDY OBJECTIVE: The efficacy of intrauterine insemination (IUI) of selected motile sperm. DESIGN: Prospective randomized sequential alternating cycle trial comparing IUI with luteinizing hormone (LH)-timed intercourse. SETTING: Clinical infertility service. PATIENTS: Couples selected included unexplained infertility (n = 73), cervical mucus hostility (n = 24), moderate semen defect (n = 110), and severe semen defect (n = 78). Two hundred eighty-five couples undertook 600 IUI cycles and 505 LH-timed intercourse. RESULTS: Overall, IUI was slightly more effective than LH-timed intercourse with a pregnancy rate of 6.2% versus 3.4% per cycle. When individual categories were considered only, IUI for severe semen defect was significantly better (5.6% versus 1.3%, P less than 0.05). The first IUI cycle was more effective when compared with both subsequent IUI cycles and the initial LH-timed cycle. Overall, 74% (27/37) of IUI pregnancies occurred in the first cycle. CONCLUSIONS: Compared with LH-timed intercourse, IUI provided little or no improved expectation of pregnancy but was beneficial in couples with severe semen defect. The occurrence of pregnancy was limited per cycle and confined essentially to the initial cycle of treatment. Continued IUI is considered to be unrewarding.     

Impact of isolated teratozoospermia on the outcome of intrauterine insemination

One thousand six hundred forty-one IUI cycles performed in 615 couples were categorized, depending on the semen analysis of the male partner, in three groups of: normozoospermia, teratozoospermia, and male factor infertility. Clinical pregnancies and live births per cycle were significantly decreased in the teratozoospermia group when compared to the normozoospermia group, with the exception of the first IUI attempt (comparable outcomes), whereas the cumulative live birth rate after four IUI attempts was significantly lower in the teratozoospermia and male factor infertility groups.     

Intrauterine Insemination: Fundamentals Revisited

Intrauterine insemination (IUI) is an assisted conception technique that involves the deposition of a processed semen sample in the upper uterine cavity, overcoming natural barriers to sperm ascent in the female reproductive tract. It is a cost-effective, noninvasive first-line therapy for selected patients with functionally normal tubes, and infertility due to a cervical factor, anovulation, moderate male factor, unexplained factors, immunological factor, and ejaculatory disorders with clinical pregnancy rates per cycle ranging from 10 to 20%. It, however, has limited use in patients with endometriosis, severe male factor infertility, tubal factor infertility, and advanced maternal age ≥ 35 years. IUI may be performed with or without ovarian stimulation. Controlled ovarian stimulation, particularly with low-dose gonadotropins, with IUI offers significant benefit in terms of pregnancy outcomes compared with natural cycle or timed intercourse, while reducing associated COH complications such as multiple pregnancies and ovarian hyperstimulation syndrome. Important prognostic indicators of success with IUI include age of patient, duration of infertility, stimulation protocol, infertility etiology, number of cycles, timing of insemination, number of preovulatory follicles on the day of hCG, processed total motile sperm > 10 million, and insemination count > 1 × 106 with > 4% normal spermatozoa. Alternative insemination techniques, such as Fallopian tube sperm perfusion, intracervical insemination, and intratubal insemination, provide no additional benefit compared to IUI. A complete couple workup that includes patient history, physical examination, and clinical and laboratory investigations is mandatory to justify the choice in favor of IUI and guide alternative patient management, while individualizing the treatment protocol according to the patient characteristics with a strict cancelation policy to limit multi-follicular development may help optimize IUI pregnancy outcomes.     

Fallopian tube sperm perfusion versus intrauterine insemination in unexplained infertility: a randomized, prospective, cross-over trial

OBJECTIVE: To compare the results of fallopian tube sperm perfusion (FSP) versus standard intrauterine insemination (IUI) in patients with unexplained infertility undergoing controlled ovarian hyperstimulation (COH). DESIGN: Randomized, prospective, cross-over study. SETTING: Reproductive medicine unit of a university hospital. PATIENT(S): Fifty-six couples with unexplained infertility. INTERVENTION(S): COH was induced by recombinant FSH and monitored by serial transvaginal ultrasound. On the day of hCG administration during the first treatment cycle, patients were randomized to either IUI or FSP. Thereafter, in case no pregnancy was achieved, patients went on being treated with FSP and IUI in alternate cycles. A maximum of four treatment cycles per couple was performed. FSP was performed using a pediatric Foley's catheter inseminating 4 mL of sperm-enriched suspension; a Kremer-Delafontaine catheter delivering 0.5 mL of sperm suspension was used for IUI. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate per cycle. RESULT(S): One hundred twenty-seven cycles (58 FSP, 69 IUI) were performed. The clinical pregnancy rate per cycle was 21.7% for IUI and 8.6% for FSP, respectively. No major adverse effects were recorded for either technique. CONCLUSION(S): After COH, FSP is less effective than IUI in couples with unexplained infertility.     

Cryopreservation of human spermatozoa within human or mouse empty zona pellucidae

OBJECTIVE: To compare the empty zona pellucidae (ZP) of different species for use in the cryopreservation of spermatozoa.Design: Prospective study. SETTING: An IVF unit of a medical center. Patient(s): Patients with azoospermia, oligoasthenozoospermia, or normal spermatozoa. INTERVENTION(s): Human and mouse ZP were prepared by evacuating the cytoplasm of oocytes or embryos. The evacuated ZP were injected with spermatozoa from patients with severe oligoasthenozoospermia and from healthy, fertile men. After the freezing and thawing procedure, the spermatozoa were aspirated outside the ZP. MAIN OUTCOME MEASURE(s): The number of spermatozoa per ZP, the number of motile sperm before freezing and after thawing, the number of sperm lost per ZP after freezing, and the sperm recovery rate were compared according to the different origins of the ZP and the sperm. RESULT(s): The number of spermatozoa, number of motile sperm before freezing and after thawing, number of sperm lost per ZP, and sperm recovery rate were comparable in all groups. The total mean number of motile sperm before freezing and after thawing, the mean number of nonmotile sperm after thawing, the mean number of sperm lost after thawing, and the sperm recovery rate were 14.5%, 11. 8%, 1.0%, 1.5%, and 82%, respectively. CONCLUSION(s): Zona pellucidae are an ideal vehicle for the cryopreservation of sperm collected by testicular sperm extraction or microsurgical epididymal sperm aspiration or from patients with severe oligoasthenozoospermia. There were no differences when human and mouse ZP were used for sperm storage.     

Treatment of refractory infertility by transcervical intrauterine insemination of washed spermatozoa

One hundred thirteen couples with either male factor, cervical factor, endometriosis, or idiopathic infertility of at least 3 years' duration were treated by intrauterine insemination (IUI) of washed motile sperm. Of the 68 women who became pregnant or completed at least three cycles of insemination, the overall pregnancy rate was 38.2%, with a mean of 1.7 treatment cycles per pregnancy. The average pregnancy rate per treatment cycle was 11.4%. Women who did not become pregnant underwent an average of 4.7 treatment cycles. Importantly, only two pregnancies occurred independent of treatment in 113 couples. In the male factor group, the pregnancy rate was 42.9% (n = 21). In women with a cervical factor, 34.5% became pregnant (n = 29); in idiopathic infertile couples or women suffering from endometriosis, there was a pregnancy rate of 38.9% (n = 18). The presence of sperm antibodies in either the male or female partner significantly lowered the pregnancy rate (6.7%) when compared with couples without sperm antibodies (50.0%). The authors conclude from these observations that IUI with washed sperm is a successful mode of therapy, especially in the case of males with asthenozoospermia.     

Experience with intrauterine insemination

Intrauterine insemination (IUI) was performed on sixty eight couples with a total of 126 cycles between July 1984 and December 1986. 14 pregnancies (20.5% per couple, 11.1% per cycle) were obtained with this therapeutical approach. In 39 couples a male factor was cause of infertility. In this group six pregnancies were obtained in 71 treatment cycles (15.1% per couple, 8.4% per cycle). Sterility due to a cervical factor was treated through IUI in 18 couples during 34 cycles. Six pregnancies (33.3% per couple 17.6% per cycle) were obtained in this group. Unexplained infertility found in 11 couples was treated with IUI in 21 cycles; two pregnancies (18.2% per couple, 9.5% per cycle) were obtained. Most pregnancies in all causes of infertility were obtained in the two first insemination cycles and no pregnancy was obtained after four cycles. Active ovulation induction was performed in the majority of the cases and only one insemination was usually accomplished. The only predictive semen parameter statistically significant in terms of pregnancy in masculine factor, was the total amount of progressive spermatozoa recovered after the washing procedure. In other words, pregnancy in more probable when less spermatozoa are lost during the procedure.