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Male Factor Infertility and ART

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Male Factor Infertility and ART Asian Journal of Andrology (2012) 14, 103–108 ß 2012 AJA, SIMM & SJTU. All rights reserved 1008-682X/12 $32.00 www.nature.com/aja REVIEW Male factor infertility and ART Herman Tournaye For years, the management and treatment of male factor infertility has been ‘experience’ and not ‘evidence’ based. Although not evidence-based, current clinical practice involves extensive use of assisted reproductive techniques (ART). Where specific treatments are not indicated or have failed, ART have become popular adjunctive treatments for alleviating male factor infertility. According to the limited evidence available, intrauterine insemination (IUI) may be considered as a first-line treatment in a couple in which the female partner has a normal fertility status and at least 13106 progressively motile spermatozoa are recovered after sperm preparation. If no pregnancy is achieved after 3–6 cycles of IUI, optimized in vitro fertilization (IVF) can be proposed. When less than 0.53106 progressively motile spermatozoa are obtained after seminal fluid processing or sperm are recovered surgically from the testis or epididymis, intracytoplasmic sperm injection (ICSI) should be performed. Although the outcome of no other ART has ever been scrutinized as much before, no large-scale ‘macroproblems’ have as yet been observed after ICSI. Yet, ICSI candidates should be rigorously screened before embarking on IVF or ICSI, and thoroughly informed of the limitations of our knowledge on the hereditary aspects of male infertility and the safety aspects of ART. Asian Journal of Andrology (2012) 14, 103–108; doi:10.1038/aja.2011.65; published online 19 December 2011 Keywords: artificial; intracytoplasmic sperm injection; insemination; in vitro fertilization; male infertility; sperm INTRODUCTION of which ART is employed to circumvent male factor infertility is In contrast to women, only a limited number of men with primary made according to sperm parameters, i.e., total motile count (TMC) male factor infertility have potentially treatable conditions. Moreover, either before or after sperm preparation. TMC is the total number of meta-analyses show that current empirical medical treatments for spermatozoa in the ejaculate or prepared sample (volume3concen- unexplained male infertility are not beneficial.1,2 However, assisted tration) multiplied by the percentage of progressive motile spermato- reproductive techniques (ART) are perceived as being more successful zoa. If the native, unprocessed semen sample contains a TMC of at than any other empirical option. When non-empirical or specific, least 13106–33106, corresponding to mild to moderate oligoasthe- well-defined treatments with proven benefit have not been successful noteratozoospermia, IUI can be proposed as a first-line approach, in a given individual with male factor infertility, ART may be used when at least 0.83106 motile sperm can be recovered after prepara- as second-line therapy. In both circumstances, ‘unexplained’ and tion, which will not always be the case in this subgroup.3 ‘explained’ male factor infertility, optimization of the female partner Compared with IVF with or without ICSI, there is good evidence that is the first action to be taken. When empiric or specific treatment IUI is a cost-effective treatment option that should be initiated before improves sperm quantity or quality to a limited degree, but not more invasive and expensive treatment alternatives are offered.4,5 As a enough for natural conception, this may be enough to allow the use recent meta-analysis has shown, in cases of male factor infertility, if the of less intensive adjunctive techniques such as intrauterine insemina- post-processing TMC is ,13106, IUI has no benefit with little expecta- tion (IUI) or in vitro fertilization (IVF), and avoid intracytoplasmic tion of conception.3 Instead of IVF, ICSI or a combination of both, i.e. a sperm injection (ICSI)—clearly, an often unappreciated benefit. split set-up, may be the initial suggestion to the couple. ART aims at increasing the probability of fertilization by bringing the spermatozoa closer to (or even within) the oocyte(s), thereby INTRAUTERINE INSEMINATION FOR MALE FACTOR bypassing some functional deficits of the male gametes. IUI and INFERTILITY IVF– embryo transfer are the most popular techniques for treating Although there are no studies available in the literature demonstrating male factor infertility. In the latter, the rate of fertilization is enhanced increased live-birth rates after IUI in male factor infertility, six rando- by microinjecting one single spermatozoon directly into the oocyte’s mized controlled trials (RCTs) showed a significant increase in preg- cytoplasm, i.e. ICSI. ICSI allows the successful use of ejaculated, epi- nancy rates after IUI, compared to timed intercourse in cases of male didymal or testicular spermatozoa to obtain fertilization in vitro. factor infertility.6 When used for unexplained infertility, ovarian superovulation coupled with IUI will increase the pregnancy rate, WHICH ART SHOULD BE USED TO CIRCUMVENT MALE but level 1 evidence does not show this to be true when ovarian super- FACTOR INFERTILITY? ovulation coupled with IUI is applied for male factor infertility.7–9 Defining when and which technique to choose remains an important However, timing by either detecting the onset of the luteinizing hor- issue. Although good prospective evidence is lacking, often the choice mone surge or administering human chorionic gonadotropin or Centre for Reproductive Medicine, University Hospital of the Dutch-speaking Brussels Free University, Brussels B-1090, Belgium Correspondence: Dr H Tournaye ([email protected]) Received: 11 May 2011; Revised: 23 August 2011; Accepted: 24 August 2011; Published online: 19 December 2011 Male factor infertility and ART H Tournaye 104 recombinant human chorionic gonadotropin is beneficial (level 1 sperm after semen preparation. A larger question arises, however, evidence).10 Both timing methods are of a similar value,11 but human ‘For male factor infertility, is there still a role for IVF in the era of chorionic gonadotropin injection has to be performed when the ICSI?’. dominant follicle(s) reach a mean diameter of 16–18 mm and is fol- The prevalence of complete fertilization failure after conventional lowed by insemination 36–42 h later. When a spontaneous leutenizing IVF is reported to be as high as 50%.27,28 Complete fertilization failure hormone peak is detected in serum, insemination has to be scheduled is an unwanted event not only because of the obvious (no hope of 24 h later, and when detected in urine, 18 h afterwards. pregnancy that cycle) impact on the couple, but also because of the There is still some controversy whether a second insemination per negative, distressing, psychological impact on the couple. The causes cycle increases the chances for conception. When combining the con- of total fertilization failure during standard IVF are related to either clusions of six RCTs in regard to male factor cases, a double insem- oocyte, sperm or laboratory factors; this is also true for ICSI cycles in ination strategy appears to be of some benefits. However, this which complete fertilization failure occurs in less than 3% of started conclusion is suspect, as it is based upon one large RCT with extremely cycles.29 Although ICSI has been put forth as the most robust tech- high pregnancy rates per cycle and its conclusion is contradictory to nique for achieving fertilization in an IVF program, the aim of repro- those from the five other RCTs, obviously casting some doubt on the ductive medicine and the specialists that practice it should always be to final recommendation.12 use the simplest and least expensive procedure with the greatest long- While good evidence is available that at least one million motile term chance of healthy children (Figure 1). spermatozoa have to be inseminated at IUI, limited evidence is avail- The cutoff values used to decide between conventional IVF and ICSI able on how to prepare semen for IUI. A meta-analysis authored by are generally experience-based. As for IUI, the TMC (in the native 13 Boomsma et al. shows that, while gradient techniques yield the high- semen sample or after sperm preparation) and sperm morphology est recovery rates, no semen preparation technique appears superior (strict criteria) have been used as criteria for determining if conven- when compared to others that are also in common use. Whether tional IVF treatment will be recommended to the couple. In this exogenous agents used to promote sperm motility, sperm capacitation regard, Kastrop et al.30 proposed a minimum motile count of at least and the acrosome reaction can improve the chances for conception one million spermatozoa in the native semen sample. Other authors after IUI for male factor infertility also remains inconclusive. For use the motile progressive count after sperm preparation as their example, even the addition of platelet-activating factor, a signaling criterion, with suggested lower limits of one million31 to 0.5 million phospholipid known to be involved in regulation of sperm-fertilizing progressive motile spermatozoa32 or even 0.2 million motile progress- potential, to sperm wash used for IUI does not result in significantly ive spermatozoa.33 When morphology is used as a guage, 5% normal 14 higher pregnancy rates. forms is the cutoff value, below which poor fertilization after conven- According to retrospective cohort studies, most pregnancies tional IVF is anticipated.34 Occasionally, a combination of morpho- achieved with IUI in women under 37 years of age will occur during logy and motile count is analyzed. Plachot et al.35 propose that at least 15,16 the first 3–4 treatment cycles. While this highlights that female age 0.5 million normal, progressively motile sperm per milliliter must be plays an important role in the success of IUI, including IUI for present in the ejaculate in order to recommend conventional IVF. 4,17,18 male factor infertility, there are few data available exploring the Contemporary strategies for deciding between IVF and ICSI are either effect of paternal age on IUI outcome.
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