The role of intrauterine insemination in male infertility

Male infertility is a common condition and intrauterine insemination (IUI) is used to treat the mild to moderate forms. Male subfertility determination is usually based on routine semen analysis but recent publications have questioned its diagnostic and prognostic accuracy as well as the effectiveness of IUI itself, as a treatment modality. We carried out a structured review of the literature to assess the current evidence regarding the diagnosis of male infertility, the effectiveness and cost effectiveness of IUI in male infertility and factors that affect the outcome of IUI. There is still uncertainty regarding the criteria for diagnosing male infertility and predicting treatment outcome based on standard semen parameters. The presence of seminal defects compromises the outcome of IUI in comparison with unexplained infertility. The total motile sperm count (TMSC) appears to have a consistent, direct relationship with treatment outcome, but there is no definite predictive threshold for success. However, it is reasonable to offer IUI as first-line treatment if TMSC is greater than 10 million when balancing the risk and cost of alternate treatments, such as in vitro fertilization (IVF). Sperm DNA studies and sperm preparation techniques warrant further studies in order to establish their clinical relevance. There are limited data on the clinical and cost-effectiveness of IUI in male infertility and large high-quality randomized controlled trials are warranted. However the difficulties in organizing such a study, at the present time, are a matter for discussion.     

Platelet-activating factor significantly enhances intrauterine insemination pregnancy rates in non-male factor infertility

OBJECTIVE: To determine the efficacy of treating semen specimens with platelet-activating factor (PAF) before IUI. DESIGN: Prospective randomized double-blinded study of PAF treatment of sperm for patients with a history of infertility undergoing IUI. SETTING: Private infertility center. INTERVENTION(S): Patients had ovulation induction therapy with clomiphene citrate (CC) or gonadotropin, two IUIs per month with PAF treatment. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates. RESULT(S): There was a significant difference in IUI pregnancy rates per cycle between control (10/56; 17.9%) and PAF (14/47; 29.8%) treatment groups in the normal male study arm. There was a significant difference in cumulative IUI pregnancy rates between control (10/35; 28.6%) and PAF (14/26; 53.9%) patient groups in the normal male study arm. There was no significant difference in IUI pregnancy rates per cycle between control (12/124; 9.7%) and PAF (14/119; 11.8%) treatment groups in the male factor study arm. There was no significant difference in cumulative IUI pregnancy rates between control (12/46; 26.1%) and PAF (14/38; 36.8%) patient groups in the male factor study arm. There was a significant difference in overall cumulative IUI pregnancy rates between control (21/81; 25.9%) and PAF (27/64; 42.2%) patient groups. CONCLUSION(S): The inclusion of PAF into the IUI sperm wash procedure significantly improves pregnancy rates. However, the significant improvement can only be shown to affect men presenting with normal semen parameters.     

Semen quality and intrauterine insemination

There is good evidence in literature that intrauterine insemination (IUI) is the best first line treatment and most cost-effective procedure for moderate male factor subfertility. It seems very difficult to identify individual semen parameters predicting the likelihood of pregnancy after IUI. This can be explained by a lack of standardization of semen analysis, but many other methodological variables may also influence IUI success rates such as the patient selection, type of ovarian stimulation and number of inseminations per cycle. A review of the literature confirmed that sperm morphology using strict criteria and the inseminating motile sperm count (IMC) after sperm preparation are the two most important sperm parameters to assess the real impact of semen quality on IUI outcome. A universal threshold level above which IUI can be performed with acceptable pregnancy rates has not been determined yet, although IUI success seems to be impaired with <5% normal spermatozoa and an IMC of <1 x 10(6). Until now, no method of sperm preparation has been shown to be superior with regard to pregnancy rate after IUI. Whether supplementation of culture media with substances such as antioxidants and platelet activating factor may improve the results remains the subject of further research.     

Spermiogramm und Seminalplasma

Semen analysis is routinely used to evaluate the male partner in infertile couples. Unfortunately, sperm measurements that discriminate between fertile and infertile men are not well defined. Treatment decisions should therefore not be based exclusively on semen analysis, except for those cases with very poor sperm parameters. Treatments such as intra-uterine insemination (IUI) or intracytoplasmic sperm injection (ICSI) can usually be performed with sufficient pregnancy rates. In couples in which even ICSI fails, intracytoplasmatic, morphogically selected sperm injection (IMSI) seems to be promising. Collecting a semen sample with high quality is always important for male patients in assisted reproduction technology (ART) programs. Sperm quality can be improved using simple methods, such as modifying sexual abstinence or collecting semen samples at home. There is new evidence that the use of seminal plasma in ART treatment may improve endometrial receptivity and consequently implantation. Sexual intercourse around the time of embryo transfer also seems to improve the clinical outcome of ART.     

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.     

Pregnancy outcome after IUI for male and idiopathic infertility using a new simplified method for sperm preparation

IntroductionIntrauterine insemination (IUI) is a valid treatment for infertility with a cumulative pregnancy rate of 40–90% after 3–10 treatment cycles.DesignWe prospectively studied the efficacy of a new simplified method for motile sperm preparation for IUI for both male causes of infertility, and for those diagnosed with idiopathic infertility.MethodsA prospective clinical trial was performed with 200 couples, with a 2–8 years history of primary infertility. One hundred couples had been diagnosed as idiopathic, while another 100 couples with male factors of infertility. Motile sperm for IUI was prepared by: (A) the classic World Health Organization self-migration (swim-up) method which includes centrifugation, or (B) the proposed simplified swim-up procedure without centrifugation. Both anti-estrogens and HMG had been used for ovarian stimulation. Depending on the cause of infertility, patients were matched one-to-one at the time of IUI, so that when a total of 100 couples had been treated of both causes of infertility, 50/100 women received sperm prepared by method A and 50/100 by method B.ResultsA statistically significant correlation was found between the percentage motile sperm of the original semen sample and the percentage of motile sperm recovered by method A (r = 0.333, P < 0.01) and B (r = 0.400, P < 0.01). A highly significant correlation (r = 0.997, P < 0.001) was found between the two methods. The pregnancy outcome after the proposed IUI procedure was not significantly different after the traditional swim-up sperm preparation.ConclusionsThe simple proposed swim-up method was as effective as the classic swim-up method, regarding the sperm recovery and pregnancy outcome, but in an easier, and faster way.     

A prospective randomized study of pregnancy rates following intrauterine and intracervical insemination using frozen donor sperm

Cryopreserved sperm have lowered fertility when compared with fresh sperm in artificial insemination by donor programs. The purpose of this study was to compare pregnancy rates following intrauterine insemination (IUI) and intracervical insemination (ICI) with cryopreserved sperm in a prospective trial using the patient as her own control. A total of 154 patients were randomized into alternating treatment cycles and underwent 238 cycles of IUI and 229 cycles of ICI. The pregnancy rate per treatment cycle was 9.7% following IUI and 3.9% following ICI. Treatment outcome was influenced by patient age, ovulatory status, and endometriosis. Pregnancy success correlated well with the post-thaw survival of sperm and the number of motile cells inseminated. In spite of having normal semen parameters, some donors were found to have markedly reduced sperm fecundity. We conclude that IUI with cryopreserved sperm can be an effective treatment for couples with infertility, genetic indications, or other reasons.     

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.     

Treatment of unexplained and mild male factor infertility by In Vitro fertilization and intra-uterine insemination

Objectives

To evaluate the efficacy of in vitro fertilization (IVF) and intra-uterine insemination (IUI) in couples with unexplained and mild male factor infertility.

Methods

One hundred fifty couples were allocated to treatment with IVF and IUI, both following the same protocol (clomiphene citrate and follicle stimulating hormone (FSH) injection) depending upon their hormonal response. The mild male factor patients were included in the study because we observed that their rate of failed fertilization was not different from those in couples with unexplained infertility. They had ovulatory cycles confirmed by recent ovulatory mid luteal phase progesterone measurement and bilateral tubal patency, which was confirmed by laparoscopy or hysterosalpingography. Men with unexplained infertility had semen analysis with a sperm concentration ≥25×10⁶/ml, motility (grdel + 2) ≥40% and normal forms ≥25%. Men with mild male factor infertility had semen analysis where only one of the above parameters was below the normal range.

Results

Among the 150 couples, 75 were treated with IVF and 75 were treated with IUI. The mean age of women allocated to IVF was 32.9 years compared to 33.2 years for the IUI treatment group. Cycle day 2 basal plasma estradiol, LH and FSH concentrations were also not different (geometric means; Estradiol 244 and 245 pmol/1, LH 4.9 and 5.3 IU/1, FSH 7.5 and 7.7 IU/1 in the IVF and IUI treatment groups, respectively).

Conclusion

IUI is the first choice of treatment for unexplained and mild male factor infertility with a lower cost and the equal efficacy as IVF. Treatment delivered within the context of a specialized IVF center will be more efficient and safer because of the potential to salvage over-responding cycles by conversion to IVF.     

Sperm DNA damage in male infertility: etiologies,assays, and outcomes

Male factor infertility is the sole cause of infertility in approximately 20% of infertile couples, with an additional 30% to 40% secondary to both male and female factors. Current means of evaluation of male factor infertility remains routine semen analysis including seminal volume, pH, sperm concentration, motility, and morphology. However, approximately 15% of patients with male factor infertility have a normal semen analysis and a definitive diagnosis of male infertility often cannot be made as a result of routine semen analysis. Attention has focused on the role of sperm nuclear DNA integrity in male factor infertility. Here we review the structure of human sperm chromatin, the etiology and mechanisms of sperm DNA damage, current tests available to assess sperm DNA integrity, and effect of sperm DNA integrity on reproductive outcomes.     

Should ICSI be used in non-male factor infertility?

There is general agreement that intracytoplasmic sperm injection (ICSI) should be used in male factor infertility cases, such as oligoasthenoteratozoospermia, presence of anti-sperm antibodies, or azoospermia, these cases being diagnosed through abnormal semen analysis. There are no randomized clinical trials comparing ICSI with IVF (or other interventions) where semen quality is so poor that IVF would not achieve fertilization. It is accepted that ICSI is the only treatment option in those circumstances. The role of ICSI where IVF can be expected to give a reasonable fertilization rate is the question that needs to be answered. The argument is whether or not ICSI should be used for all cases of infertility. This paper proposes and strongly supports the use of ICSI for all indications. Considerations of fertilization and embryo development, cost effectiveness and safety will be clearly discussed.     

Assessment of male serum anti-Mullerian hormone as a marker of spermatogenesis and ICSI outcome

Objective.?To assess serum anti-Mullerian hormone (AMH) as a marker of spermatogenesis among fertile and infertile males, as well as its relation to ICSI outcome.

Methods.?A total of 77 male partners of infertile couples seeking infertility treatment were recruited for this study. They were classified according to the WHO criteria of semen analysis into three groups; azospermia, oligospermia, and normal. All participating patients had a serum assay of the level of AMH. Thirty-three couples out of the previously mentioned 77 couples underwent controlled ovarian stimulation and ICSI.

Results.?There were 41 patients with azospermia, 14 patients with oligospermia, and 22 patients with normal count. There was no significant difference among the three groups regarding the AMH levels. There was no significant correlation between the AMH levels from all patients and the sperm concentration (rho?=?0.03, p?=?0.82). Among patients who underwent ICSI, there was no significant correlation of the AMH with the age, sperm concentration, fertilisation percent or number of embryos. The age of male partners was significantly correlated with sperm concentration, fertilisation percent and the total number of embryos. In the logistic regression model used, serum AMH had no significant relation to clinical pregnancy.

Conclusion.?Male serum AMH levels are not indicative of spermatogenesis and cannot differentiate between fertile and infertile males. Serum AMH levels were not predictive of ICSI outcome as well.     

Semen quality before and after processing by a swim-up method: relationship to outcome of intrauterine insemination

Twenty-five couples with normal semen analyses and postcoital tests of less than or equal to 3 motile sperm/high-power field were treated by intrauterine insemination (IUI) with sperm prepared by a swim-up method. Eight women conceived (32%). Influence of semen parameters both before and after swim-up, patient age, and duration of infertility on outcome of IUI was assessed with logistic discriminant analysis. The percent motility of sperm after swim-up allowed significant differentiation of pregnant and nonpregnant patients (P = 0.0009). For patients with greater than 79% motility after swim-up, discrimination provided by post-swim-up motility (P = 0.0063) was enhanced by inclusion in the analysis of either total number of motile sperm used for insemination (P = 0.0021) or sperm concentration after swim-up (P = 0.0019), Predictions of nonpregnancy and pregnancy were correct at rates of 93.3 and 70%, respectively. There were no significant differences between semen parameters of conception and nonconception cycles of patients who conceived.     

Time intervals between semen production,initiation of analysis,and IUI significantly influence clinical pregnancies and live births

PurposeDoes IDEF mapping help monitor the technical process of IUI and explore the potential improvements which might contribute to increased pregnancy and live birth rates?MethodRetrospective analysis of 1729 homologous IUI cycles of couples attending a fertility clinic in a university hospital setting. Standardized conventional semen parameters were analyzed and the semen samples prepared via discontinuous density gradient centrifugation.ResultsThere was no significant association between sperm concentration, motility and morphology (analysis phase), and pregnancy outcome. Only female and male ages were significantly associated with the pregnancy outcome. There was a significant difference in the odds on clinical pregnancies and live births when analysis was ≤ 21 min initiated, and < 107 min between sample production and IUI, adjusted for male and female age.ConclusionsAdjusting for the couple’s age, we could show that time intervals between semen production and analysis and IUI when kept low significantly influenced clinical pregnancies and live births.     

Insemination data on men with varicoceles.

OBJECTIVE: To determine possible benefits of sperm processing and intrauterine insemination (IUI) for a group of men with a varicocele history who had not achieved a pregnancy by natural coitus (mean duration of infertility 42.2 months). DESIGN: A retrospective study including infertile men with varicoceles who were classified by their semen analyses and sperm penetration assays (SPAs). SETTING: Private practice of infertility. PATIENTS: Seventy-one infertile couples. The husbands had a varicocele history and were grouped into four clinical categories (14 untreated, 5 medical treatment, 34 varicocelectomies, and 18 varicocelectomies plus medical treatment). The wives were studied or treated before IUI. INTERVENTIONS: Varicocelectomies were performed on the males when indicated. Female studies included laparoscopies as indicated intrauterine insemination with Tomcat catheter (Sherwood Medical, St. Louis, MO) was performed in all cases. MAIN OUTCOME MEASURES: Overall pregnancy rates (PRs) and fecundity rates with sperm processing and IUI. RESULTS: Six pregnancies occurred with 66 cycles of sperm processing and IUI among 28 men with normal SPAs (PR 21%, fecundity rate = 0.09). In contrast, there were no pregnancies with 121 cycles among 43 varicocele patients with abnormal SPA results or with low values for all three semen parameters. CONCLUSIONS: Sperm processing and IUI may be beneficial for selected patients with varicoceles who had not achieved a pregnancy by coitus.     

Factors predictive of clinical pregnancy in the first intrauterine insemination cycle of 306 couples with favourable female patient characteristics

Abstract

The objective of this study was to evaluate the factors predictive of clinical pregnancy in the first superovulation/intrauterine insemination (SO/IUI) cycle of couples with favourable female characteristics. We analyzed retrospectively the first SO/IUI cycle of 306 infertile couples with mild male factor infertility and unexplained infertility. The women had a favourable prognosis in terms of ovarian reserve.

Univariate logistic regression analyses identified body mass index (BMI) [odds ratio (OR) = 0.9, P = 0.014], sperm concentration [OR = 1.007, P = 0.007] and inseminating motile sperm count (IMC) [OR = 1.007, P = 0.032] as significant predictive factors of clinical pregnancy. Multivariate logistic regression analysis identified BMI [OR = 0.87, P = 0.008] and sperm concentration [OR = 1.008, P = 0.011] as significant factors. Pregnant and non-pregnant groups did not differ significantly in terms of the age and smoking status of the woman, duration and type of infertility, length of the stimulation, total gonadotropin dosage or antral follicle count. Of the female characteristics investigated, BMI was the most significant predictive factor of clinical pregnancy in the first SO/IUI cycle of couples with unexplained or mild male factor infertility and favourable female characteristics. In overweight women, weight loss should be advised before starting SO/IUI. Sperm concentration and IMC were significant male predictive factors for clinical pregnancy in the first SO/IUI.     

Pre-washing catheter dramatically improves the post intrauterine insemination pregnancy rate

ObjectiveTo analyze the effectiveness of pre-washing the intrauterine insemination catheters on IUI outcome.Patients and methodsInfertile couples (n = 322) involved in a IUI program were included in the study. IUI indications were cervical factors, ovulation dysfunction, cryopreserved semen and unexplained infertility. Every other week for two years, IUI catheters were washed with culture medium prior to intrauterine sperm insemination.Result(s)Only the first IUI for each couple were analyzed. Washing the catheter, prior to use, resulted in a 49.7% increase in clinical pregnancy rate (22.0% vs 14.7% P < 0.05). This result is observed with fresh sperm (15.7% vs 11.1%) and frozen-thawed sperm as well (31.1% vs 19.8%). The early pregnancy termination rate was similar in all groups.Discussion and conclusionPre-washing the catheter before IUI should be recommended in Good Laboratory Practice Guidelines as it is already the case for embryo transfer catheters. This raises the problem of washing all single-use devices, in contact with gametes or embryos during IVF.     

The value of fallopian tube sperm perfusion in the management of mild-moderate male factor infertility

ObjectiveTo investigate whether fallopian tube sperm perfusion (FSP) would improve pregnancy rates compared with standard intrauterine insemination (IUI) in cases of male factor infertility.MethodsIn a randomized controlled trial at a university teaching hospital in Egypt, 120 couples with mild or moderate male factor infertility underwent a mild controlled ovarian stimulation protocol (clomiphene citrate plus human menopausal gonadotropin). Women were randomly allocated to group 1 (FSP via Foley catheter with 4 mL of inseminate) or group 2 (standard IUI with 0.5 mL of inseminate) (n = 60 for both). The main outcome measure was clinical pregnancy rate.ResultsThere were no significant differences between the groups in terms of baseline clinical characteristics, semen parameters, or characteristics of stimulation cycles. The pregnancy rate was significantly higher in group 1 than in group 2 (16 [26.7%] vs 7 [11.7%]; P < 0.04). There was no significant difference in the incidence of multiple pregnancy, abortion, or ectopic pregnancy between the groups.ConclusionFallopian tube sperm perfusion is an effective technique in the management of mild–moderate male factor infertility and should, therefore, be considered before resorting to more sophisticated techniques of assisted reproduction.     

Preparation of oligozoospermic and/or asthenozoospermic semen for intrauterine insemination using the SpermPrep semen filtration column.

OBJECTIVE: To improve the quality of oligozoospermic and/or asthenozoospermic semen by the SpermPrep (Fertility Technologies Inc., Natick, MA) semen filtration column. DESIGN: The SpermPrep column was applied for semen manipulation in oligozoospermia and/or asthenozoospermia (sperm count less than 20 x 10(6)/mL, sperm motility less than 40%). After concentration of motile sperm using a 40% Percoll density gradient centrifugation, the sperm suspension was filtered through the SpermPrep column. The percentage yield of motile sperm by the SpermPrep method was compared with those by a two-layer Percoll density gradient (Pharmacia, Uppsala, Sweden) centrifugation and a swim-up method. Infertile couples with poor quality semen were treated with intrauterine insemination (IUI) with motile sperm by the three preparations through three cycles. SETTING: Department of Obstetrics and Gynecology, Osaka University Hospital. PATIENTS: Twenty-one couples with long-standing infertility because of poor quality semen. MAIN OUTCOME MEASURE: Recovery of motile sperm, sperm motility, and outcome of IUI were evaluated among three semen preparations. RESULTS: Motility was improved by the SpermPrep method in 32 of 33 cases of oligozoospermia and/or asthenozoospermia. Percentage yield of motile sperm by the SpermPrep method was significantly greater than those by the two-layer Percoll density gradient and swim-up methods (42.7 +/- 4.6 versus 22.1 +/- 3.1 and 13.8 +/- 3.5), but there is no significant difference in the sperm motility among three semen preparations. After one treatment cycle for each preparation, 2 of 21 women conceived after IUI with motile sperm separated in the SpermPrep method. CONCLUSIONS: The SpermPrep method is an improved semen manipulation method for oligozoospermia and/or asthenozoospermia.     

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.