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.     

Electroejaculation in combination with in vitro fertilization and gamete micromanipulation for treatment of anejaculatory male infertility.

OBJECTIVE: Failure to ejaculate may be overcome by use of electroejaculation. However, such semen samples are often unsuitable for therapies like intrauterine insemination. The combination of electroejaculation with in vitro fertilization, including gamete micromanipulation, should improve chances of fertilization and pregnancy in such cases. STUDY DESIGN: Within a private infertility clinic electroejaculation in combination with intrauterine insemination was carried out in 18 cycles (10 couples). Four couples went on to receive therapy by electroejaculation plus in vitro fertilization, along with six other couples (15 cycles total) with semen too poor for intrauterine insemination. RESULTS: One term pregnancy arose in the electroejaculation-intrauterine insemination group, and one term pregnancy plus one continuing pregnancy arose from two couples (three cycles) who underwent in vitro fertilization with conventional insemination after electroejaculation. Six couples (nine cycles) had embryos arising only from gamete micromanipulation transferred, and this yielded two term pregnancies, one spontaneous abortion, and a biochemical pregnancy. Two couples (three cycles) failed to achieve fertilization even with micromanipulation; however, donor-inseminated eggs gave rise to two term pregnancies and one continuing pregnancy in these patients. CONCLUSIONS: This report confirms the feasibility of in vitro fertilization in conjunction with electroejaculation and extends the therapy to incorporate gamete micromanipulation.     

Treatment by assisted conception of severe male factor infertility due to spinal cord injury or other neurologic impairment

Purpose This retrospective study evaluated the pregnancy rates of 23 couples with male factor infertility due to traumatic spinal cord injury (N = 21), multiple sclerosis (N = 1) or transverse myelitis (N = 1).Methods Ovulation induction by clomiphene citrate or gonadotropins was used in combination with intrauterine insemination as an initial approach for assisted conception in all but one couple.Results Six pregnancies occurred in 60 cycles of intrauterine insemination (mean of 2.6 cycles). In this group, the cumulative pregnancy rate was 26%. Six couples who failed after a total of 33 intrauterine insemination cycles (mean of 5.5 cycles), and 1 couple with no previous intrauterine insemination cycles, initiated 10 cycles of in vitro fertilization (mean of 1.4 cycles). In this group, five pregnancies occurred. The pregnancy rate was 71%.Conclusion We conclude that ovulation induction in combination with intrauterine insemination offers an effective initial therapy of severe male factor infertility due to spinal cord injury.Presented at the 50th Annual Meeting of the American Fertility Society, November 5–10, 1994, San Antonio, Texas.     

Superovulation with buserelin and gonadotropins dramatically improves the success rate of intrauterine insemination with husband's washed semen

The purpose of this study was to determine the effectiveness of intrauterine insemination with husband's washed semen during stimulated cycles using a combined treatment of GnRH agonist (buserelin) and gonadotropins. 47 infertile couples were studied; 25 couples were treated with buserelin and gonadotropins (study group) and 22 (control group) received clomiphene citrate alone. Indications for treatment, in both groups, were male subfertility, cervical factor or unexplained infertility. For sperm preparation, the same swim up technique in both groups was used. In the study group, 15 pregnancies were achieved (pregnancy rate: 60%) whereas only 5 pregnancies were achieved in the control group (pregnancy rate: 22.7%) (p less than 0.01). The pregnancy rate per cycle was 17.6 and 4.8 respectively (p less than 0.01). The mean number of follicles per cycle (+/- SEM) was 3.6 +/- 0.2 and 1.7 +/- 0.07, respectively (p less than 0.0005). Comparing successful and unsuccessful cycles a difference was observed only among the levels of 17 beta E2, both per cycle and per follicle/cycle (1075 +/- 165.4 vs 721 +/- 57.6 and 319.8 +/- 42.6 vs 219.9 +/- 17.8; p less than 0.01 and p less than 0.0005 respectively). The authors conclude that intrauterine insemination with washed sperm during stimulated superovulatory cycles is a successful mode of therapy in all couples with infertility not associated with anatomic damage of the adnexa or with chronic anovulation.     

Superovulation with intrauterine insemination in the treatment of infertility: a possible alternative to gamete intrafallopian transfer and in vitro fertilization

In vitro fertilization and embryo transfer (IVF-ET) and gamete intrafallopian transfer (GIFT) are used to treat intractable infertility in women with no distortion of the pelvic viscera, despite the lack of controlled trials demonstrating efficacy. The mechanism of any purportedly enhanced cycle fecundity in ovulatory women without significant distortion of the pelvic viscera is unclear, but both GIFT and IVF-ET increase the number of male and female gametes at the site of fertilization. Intrauterine insemination (IUI) during human menopausal gonadotropin (hMG)-stimulated superovulatory cycles has similar potential but does not require oocyte retrieval. To evaluate the possibility that simply increasing the number of gametes at the site of fertilization might account for pregnancies attributed to IVF-ET and GIFT, the authors retrospectively analyzed the outcome of couples undergoing IUI during hMG cycles between 1983 and 1986 in women with normal pelvic anatomy. IUI during hMG-stimulated cycles yielded a cycle fecundity (f) of 0.17 for endometriosis, 0.29 for cervical factor, and 0.19 for idiopathic infertility, which approaches the fecundity of normal women and equals or exceeds that reported for IVF-ET and GIFT. The authors conclude that treatment with IUI in hMG cycles, alleviating the need for invasive oocyte retrieval, should be considered for inclusion in a randomized, controlled trial in comparison with IVF-ET and GIFT.     

Experience with intrauterine insemination for cervical factor and oligospermia

In the past 100 years, interest in intrauterine insemination for cervical factor has waxed and waned. Recently the advent of in vitro fertilization, with improved methods of sperm washing and preparation, has revived interest in intrauterine insemination as a modality for the treatment of infertility. Twenty-seven couples with infertility resulting from cervical factor and/or oligospermia were entered into our intrauterine insemination protocol. A total of 107 intrauterine inseminations were performed in 85 menstrual cycles. Nineteen couples with a cervical factor as the major factor in their infertility experienced three pregnancies (16%). The remaining eight couples who had oligospermia with or without cervical factor produced no pregnancies. No major complications occurred from this procedure. In view of the low pregnancy rate experienced in this study, we must seriously question the value of intrauterine insemination in the treatment of cervical factors and/or oligospermia.     

Intrauterine insemination is not useful in oligoasthenospermia

A prospective randomized study was conducted in 47 couples with infertility due to subnormal semen to compare luteinizing hormone (LH)-timed intrauterine insemination with LH-timed natural intercourse. No pregnancy occurred in 114 cycles of intrauterine insemination with washed sperm. Only one patient conceived during 1 of the 124 natural intercourse cycles. The only complication that occurred after intrauterine insemination was mild abdominal cramp in 3 cycles. The authors conclude that intrauterine insemination is not useful in the management of subfertility due to oligoasthenospermia.     

Effectiveness of stimulated menstrual cycles and Percoll sperm preparation in intrauterine insemination

To examine the usefulness of intrauterine insemination in women with various fertility factors, we retrospectively analyzed data from women treated during 1986 and 1987. Ninety-three patients underwent 1-11 cycles of single or double procedures, for a total of 423 inseminations in 263 treatment cycles. Twenty-six patients (28%) conceived, for a 10% total pregnancy rate per cycle, with 58% of the pregnancies resulting from double inseminations per cycle. An average of two treatment cycles was required to achieve pregnancy. Eight pregnancies (31%) occurred in spontaneous cycles, while 18 (69%) occurred in stimulated cycles. While clomiphene citrate therapy was useful in anovulatory patients, it was of no benefit in ovulatory patients being treated with intrauterine insemination. Human menopausal gonadotropin therapy was of benefit in both ovulatory and anovulatory patients when combined with intrauterine insemination. The live birth rate was higher (75%) in spontaneous cycles than in stimulated cycles (44%). Semen preparation was accomplished by sperm washing in 61% of the pregnancies and by Percoll preparation in 39%. The effectiveness of the discontinuous Percoll gradient for semen preparation for insemination was suggested by a pregnancy rate of 9% per cycle. While the mean sperm count in the pregnant group was 44 million, successful pregnancy was accomplished with a double insemination of 880,000 and 1.16 million rapidly progressive sperm in the first and second inseminate, respectively. The data confirm the important role of intrauterine insemination for the treatment of infertility.     

Intrauterine inseminations with washed human spermatozoa

The success of intrauterine inseminations with washed human spermatozoa was evaluated in four groups of patients. The first two groups were couples in whom either the man or the woman had detectable circulating sperm-agglutinating antibodies. The third group included couples where the woman exhibited hostile or absent cervical mucus, whereas the fourth group represented couples with oligozoospermic males. The couples underwent 3.7 +/- 2.1 insemination cycles, with a 30% overall pregnancy rate for all four groups. Intrauterine inseminations of women with hostile cervical mucus yielded a 68% conception rate. Couples with either male or female serum sperm-agglutinating antibodies showed 25% and 40% pregnancy rates, respectively. However, none of the couples with oligozoospermic males achieved pregnancy. Intrauterine inseminations with washed human spermatozoa thus represent a satisfactory method of achieving pregnancy in women with hostile cervical mucus and in couples with circulating sperm agglutinating antibodies. Couples in whom oligozoospermia has been identified as the principal cause of infertility do not seem to benefit from this therapy.     

Intrauterine insemination as a treatment of infertility in women with antisperm antibodies.

Twenty-four women with infertility caused by antisperm antibodies were treated by homologous intrauterine insemination. Initially, all the women had timed intrauterine insemination by washed spermatozoa for three cycles. The pregnancy rate per couple was 4.20%. The remaining 23 patients received a combined treatment of chlomiphene citrate and intrauterine insemination for three cycles, which did not increase the pregnancy rate per couple and per cycle (4.3% and 1.4% respectively). Thereafter, the remaining 22 patients received a combined treatment of hMG and intrauterine insemination for another three cycles which resulted in a pregnancy rate per cycle (6.1%) and per couple (18.20%) that was significantly greater (P less than 0.01). We conclude that infertile women with antisperm antibodies can benefit after a trial of induction of multiple follicular development with hMG in combination with intrauterine insemination.     

Case series of a single centre's treatment of ovulatory infertility with clomiphene citrate and intrauterine insemination in 2002

The present paper reports a single department's retrospective case series of all clomiphene citrate (CC) combined with intrauterine insemination (IUI) treatment cycles for ovulatory infertility performed during 2002. Thirty-eight couples with unexplained, endometriosis, male or unilateral tubal factor infertility had undergone 71 cycles of CC and IUI. The clinical and ongoing cycle pregnancy rates were 20 and 17%, respectively. Seven percent of the clinical pregnancies were multiple pregnancies, with all multiple pregnancies being twin gestations. The current use of CC and IUI is an effective early treatment option in couples with ovulatory infertility presenting to our department.     

Intrauterine insemination of washed husband's spermatozoa: a controlled study

We performed intrauterine insemination with washed husband's spermatozoa in 27 couples with clear evidence of impaired sperm mucus interaction due to cervical hostility or immunologic male subfertility and in 30 couples with subnormal semen, but optimal cervical mucus qualities. In each couple insemination cycles were alternated with cycles during which normal intercourse took place. Both types of cycles were monitored for LH. When a clear rise of LH levels could be detected, either IUI was scheduled or intercourse advised for the following day. In the male subfertility group no difference between the pregnancy rates of insemination and intercourse cycles was present. In the group with impairment of sperm-mucus interaction, the pregnancy rate of the insemination cycles was 16%, whereas no pregnancies occurred during intercourse cycles.     

The role of the new reproductive technologies including IVF and GIFT in endometriosis

In the context of the pathophysiology of endometriosis, the technology of IVF-ET and GIFT appears to offer a promising alternative for infertility associated with endometriosis in situations refractory to conventional medical or surgical therapy. The success rate of IVF with respect to follicular response, oocyte recovery, fertilization rate, and pregnancy rate in mild-to-moderate (stages I to II) disease is comparable to patients with tubal disease. However, compromise of oocyte recovery and fertilization appears to be present in severe-extensive cases (stages III to IV) implying an impairment of reproductive potential in advanced disease. In all stages of endometriosis, prior therapy, either medical or surgical, offers the best prognosis for an IVF or GIFT attempt. Surgical therapy with operative endoscopy at the time of oocyte retrieval offers a reasonable prognosis for treatment-independent pregnancy in cases of active endometriosis. The GIFT procedure bypasses an unfavorable peritoneal environment in stages I to II endometriosis without anatomic distortion or compromise of fallopian tube function. Pretreatment with GnRH analogues prior to ovulation induction is valuable in suppression of active disease as well as in inducing improved homogeneity of follicular response in IVF or GIFT cycles.     

Análisis de los factores de influencia sobre el resultado de 500 ciclos de inseminación intrauterina homóloga

Objective

To evaluate the results and analyse different factors influencing pregnancy rate using homologous intrauterine insemination.

Subjects and methods

Retrospective analysis of 500 homologous intrauterine insemination cycles in 183 infertile couples. Only one insemination per stimulated ovarian cycle was performed in patients with: mild endometriosis, ovulatory factor, male subfertility or unexplained infertility. We studied female age, duration of infertility, stimulation protocol, number of cycle, number of preovulatory follicles, motile sperm count and endometrial thickness related to pregnancy rate.

Results

Pregnancy rate per couple was 24% and per intrauterine insemination 9%, 11% was multiple pregnancies. Best outcome has been got in women younger than 37 years (P=.048) and in cycles with more than one preovulatory follicle. Other studied factors did not have influence in homologous intrauterine insemination outcome.

Conclusions

Female age is a prognostic factor for homologous intrauterine insemination with poor outcome in women older than 38 years. Cycles with more than one preovolatory follicle have better outcome. No differences in pregnancy rate have been achieved with motile sperm count over 1.5 millions/0.3 ml.     

A controlled trial of intrauterine insemination for cervical factor and male factor: a preliminary report

In a prospective, randomized, controlled trial, we evaluated the efficacy of intrauterine insemination (IUI) in 54 couples with cervical factor (CF) infertility and in 19 couples with male factor (MF) infertility. The diagnoses were confirmed by strict criteria and all other etiologies of infertility were ruled out prior to entry. Patients served as their own controls with alternating cycles of washed sperm IUI and whole-ejaculate intracervical insemination (ICI). In 113 paired cycles (mean 2.1 pairs/patient; range 1-7 paired cycles), 13% (n = 7) of CF patients became pregnant by IUI, 7% (n = 4) by ICI, and 6% (n = 3) by intercourse after missing inseminations. Seventy-one percent of IUI pregnancies occurred in the first 2 months. In 45 paired cycles for MF patients (mean 2.4 pairs/patient; range 1-6 paired cycles), two patients conceived, both in the first IUI cycle. These data suggest that pregnancies resulting from IUI occur during early treatment cycles.     

Intrauterine insemination as treatment for antisperm antibodies in the female

Ninety-one women with long-standing infertility in the presence of humoral antisperm antibodies (ASA) underwent 473 cycles of intrauterine insemination of washed sperm (IUI), resulting in 26 pregnancies. Nine pregnancies were achieved in 67 women who underwent 285 IUI during unstimulated cycles (13% pregnancy rate; 3% pregnancy/cycles of treatment). Twenty women underwent 86 IUI after clomiphene citrate (CC) stimulation, resulting in 6 pregnancies (30%; 7% per cycle), while 28 underwent 102 cycles of IUI after human menopausal gonadotropins (hMG) stimulation, resulting in 11 pregnancies (39%; 11% per cycle). Twenty-one of the 26 pregnancies (81%) were achieved in the first 2 IUI cycles. During unstimulated and CC IUI cycles, all pregnancies occurred in the first two cycles of treatment, while with hMG stimulation pregnancies also occurred in the third, fourth, and fifth IUI cycles. Nine of these 91 women subsequently conceived spontaneously, and three others conceived through in vitro fertilization. Only 6 of the 38 pregnancies resulted in spontaneous abortion (16%). Thus, pregnancies achieved in women with ASA have no increased risk of abortion.     

Homologous artificial insemination for oligoasthenospermia: a randomized controlled study comparing intracervical and intrauterine techniques

Homologous artificial insemination (AIH) is used to treat infertility caused by oligoasthenospermia, despite the lack of controlled studies confirming its benefit. This prospective randomized controlled trial was undertaken to determine whether intracervical (IC-AIH) or intrauterine (IU-AIH) homologous artificial insemination improves pregnancy rates in couples with infertility attributable to oligoasthenospermia alone. Twenty couples were randomized to receive IC-AIH or IU-AIH. Sixty-three insemination cycles were completed. During the same study period, 35 cycles with timed vaginal intercourse alone were assessed. Four pregnancies occurred, all following timed vaginal intercourse. No pregnancies resulted from IC-AIH or IU-AIH. This suggests that neither IC-AIH nor IU-AIH is of benefit when oligoasthenospermia is the cause of infertility. Pregnancies previously attributed to AIH may also have been conceived as a result of vaginal intercourse. This confounding effect on the results of AIH should always be considered.     

Artificial insemination: a comparison of pregnancy rates with intrauterine versus cervical insemination and washed sperm versus serum swim-up sperm preparations

A four-cycle artificial insemination protocol was undertaken, with luteinizing hormone (LH) timing, to compare washed sperm and serum swim-up sperm preparations and cervical and intrauterine insemination. Of the 75 patients entered into the protocol series, 63 finished all 4 cycles. During the treatment period, 24 patients became pregnant, 20 of whom were donor (AID) pregnancies (out of 52 patients) and 4 were husband (AIH) pregnancies (out of 11 patients). Seventy-five percent of the pregnancies were intrauterine, whereas only 25% were from cervical inseminations. Sixty-two percent of the pregnancies were due to serum swim-up sperm preparations, and 38% were due to washed sperm preparations. The data indicate substantially higher pregnancy rates can be obtained with intrauterine insemination and suggest that additional studies are necessary to determine if the method of sperm preparation significantly influences pregnancy rates.     

Results of artificial insemination at home by the partner with cryopreserved donor semen: a randomized study

The use of cryopreserved semen offers the possibility of home insemination by the instructed partner. A comparative study was designed whereby participants were randomly allocated to use home or clinic insemination for six cycles. If no pregnancy had occurred after six cycles, the site of insemination was switched to the opposite location for a maximum of six further cycles. Fifty-three women with primary infertility fulfilling all entry criteria entered the study. In the first 6 cycles out of 29 home starters, 13 pregnancies were conceived, whereas in 24 clinic starters 11 pregnancies occurred, yielding no statistical difference in pregnancy rate. Of 138 couples who did not meet the criteria in the same period, 45 opted for home insemination, resulting in 20 home-inseminated pregnancies. Again, for comparable subgroups no statistical difference in pregnancy rate between home and clinic insemination was found.     

Pretreatment of sperm with human follicular fluid for borderline male infertility

To test the usefulness of human follicular fluid (FF) in treating male infertility, we incubated washed sperm specimens from 31 couples undergoing intrauterine insemination (IUI), for male and/or unexplained infertility, with either FF or Ham's F-10 medium (Gibco, Grand Island, NY), in alternating cycles in a randomized manner. Semen specimens from 28 men were incubated with either medium or FF. Incubations with FF have increased sperm penetration assay (SPA) scores from 24.8 +/- 17.3 to 34.3 +/- 13.6 (P less than 0.01). Incubation with heat-inactivized FF also has increased SPA scores, although to a lesser extent than noninactivized FF. Seventeen pregnancies occurred in the 31 couples treated by IUI (54.8%), 16 of them in FF-treated cycles (51.6%) and one in "control" IUI cycles (3.2%, P less than 0.01). All pregnancies occurred within four treatment cycles. Thus, IUI after sperm wash and preincubation with FF may be suggested for four to six cycles to couples with male factor and/or unexplained infertility who are reluctant to resort to artificial insemination by donor or adoption, before attempting the more costly and complex in vitro fertilization-embryo transfer procedure.