Forms Of Male Factor Infertility Research Articles

Citation classics in Fertility and Sterility, 1975–2004

Citation classics in Fertility and Sterility, 1975–2004

Rescue of spermatogenesis arrest in azoospermic men after long-term gonadotropin treatment

Several studies have shown that FSH treatment can improve sperm production quantitatively and increase the spermatogonial population in oligozoospermic men with normal hormonal profiles. In this study, we describe the results of long-term gonadotropin therapy of normogonadotropic patients with nonobstructive azoospermia.

Techniques for surgical retrieval of sperm prior to ICSI for azoospermia.

Azoospermia, the absence of sperm in ejaculated semen, is the most severe form of male factor infertility and is present in approximately 5% of all investigated infertile couples. The condition is currently classified as "obstructive" or "non-obstructive", although it is important to also consider the specific aetiology of each individual case. Some cases of obstructive azoospermia are treatable using microsurgical reconstruction of the seminal tract (for example, vasectomy reversal). Unreconstructable obstructive azoospermia and non-obstructive azoospermia have historically been relatively untreatable conditions that required the use of donor spermatozoa for fertilisation. The advent of intra-cytoplasmic sperm injection (ICSI), however, has transformed treatment of this type of severe male factor infertility. Sperm can be retrieved for ICSI from either the epididymis or the testis depending on the type of azoospermia. To evaluate the efficacy of the various surgical retrieval techniques for men with obstructive or non obstructive azoospermia prior to ICSI. Electronic searches of the Cochrane Menstrual Disorders and Subfertility Group specialised register of controlled trials, CCTR, MEDLINE, EMBASE, and Bio extracts were performed to identify relevant randomised controlled trials (RCTs). Attempts were also made to identify trials from the National Research Register, the Clinical Trial Register and the citation lists of review articles and included trials. The first or corresponding author of each included trial was also contacted for additional information. Trials were included if they were randomised and compared the effectiveness of sperm retrieval techniques in men with azoospermia prior to ICSI. Due to the lack of RCTs non-randomised trials, who used the participants as their own control, were also considered in the review but not included in the meta-analysis. Trials of surgically extracted sperm versus ejaculated sperm or of diagnostic biopsies with no sperm parameter information were excluded. One RCT was included in this systematic review which compared micropuncture with nerve stimulation versus microsurgical epididymal sperm extraction. Pregnancy rate, sperm retrieval adequate for ICSI and fertilisation rate were primary outcomes. Another RCT comparing microsurgical epididymal sperm extraction versus testicular sperm extraction, was excluded from the meta-analysis due to poor randomisation. Seven non-randomised comparative trials were also identified and included. Main outcomes were pregnancy rate, sperm retrieval adequate for ICSI, fertilisation rate and implantation rate. Quality assessment and data extraction were performed independently by two reviewers. Meta-analysis was performed using odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Data unsuitable for meta-analysis was reported as descriptive data and was also included for discussion. One small RCT comparing two epididymal techniques gave limited evidence that microsurgical epididymal sperm aspiration (MESA) achieved significantly lower pregnancy (OR 0.19, 95% CI 0.04-0.83) and fertilisation rates (OR 0.16, 95% CI 0.05-0.48) than the micropuncture with perivascular nerve stimulation technique. However the small number of participants included and the questionable methodology of this RCT make it impossible to make a definitive statement about the relative merits of either treatment. There is insufficient evidence to recommend any specific sperm retrieval technique for azoospermic men undergoing ICSI. Further randomised trials are warranted, preferably multi-centred trials.

Intracytoplasmic sperm injection: A novel treatment for all forms of male factor infertility: Palermo G.D.; Cohen J.; Alikani M.; Adler A.; Rosenwaks Z. Fertil Steril 1995 63/6 (1231–1240)

Intracytoplasmic sperm injection: A novel treatment for all forms of male factor infertility: Palermo G.D.; Cohen J.; Alikani M.; Adler A.; Rosenwaks Z. Fertil Steril 1995 63/6 (1231–1240)

Chromatin packaging and morphology in ejaculated human spermatozoa: evidence of hidden anomalies in normal spermatozoa

This study aimed to investigate the association between anomalies in sperm chromatin packaging, morphology and fertilization in patients undergoing routine in-vitro fertilization (IVF) or subzonal insemination (SUZI). Sperm chromatin packaging was assessed using chromomycin A3 (CMA3), a fluorochrome specific for guanine-cytosine rich sequences of DNA. One hundred to 150 sperm cells were assessed in 55 patients to compare sperm chromatin packaging and morphology to fertilization after IVF or SUZI. When the morphology and CMA3 fluorescence of individual spermatozoa was assessed, > 75% of the macrocephalic sperm fluoresced in all patients. In contrast, a mean of 37% of the spermatozoa with normal morphology fluoresced in IVF patients compared with 58% of the normal spermatozoa in male factor patients treated by SUZI. SUZI patients displaying a high fluorescence (> 70%) in their spermatozoa also had a significantly lower fertilization rate. Lower packaging quality in morphologically normal spermatozoa may represent a major limiting factor in the fertilizing ability of male factor patients. This study confirms that a high percentage of CMA3 positivity is present in certain forms of male factor infertility and that such a test may be used to distinguish separate populations in morphologically normal spermatozoa.

Evolution of the sperm aster after microinjection of isolated human sperm centrosomes into meiotically mature human oocytes.

This study examined the feasibility of isolating and transferring the centrosome-containing region of spermatozoa to mature human oocytes. The findings demonstrate that individual sperm centrosomes can be transferred and are capable of nucleating maternal tubulin to form a well-developed sperm aster in the recipient oocyte. The results are discussed with respect to centrosome function in early human development and applications in clinical in-vitro fertilization in the treatment of certain forms of male factor infertility.

Intracytoplasmic sperm injection: a novel treatment for all forms of male factor infertility

To demonstrate the effectiveness of intracytoplasmic sperm injection to treat male factor infertility and to report on the achievement of fertilization and pregnancy compared with standard in vitro insemination. Controlled clinical study. Couples suffering from male factor infertility treated in an academic research environment. Two hundred twenty-seven couples in whom the male partners were presumed to be the cause of repeated failed attempts at IVF or whose semen parameters were unacceptable for conventional IVF. Oocytes for this study were harvested after superovulation with GnRH agonist and gonadotropins. After removing the cumulus cells, a single spermatozoon was injected directly into the cytoplasm of metaphase II oocytes, and the outcome was analyzed in terms of semen parameters and origin of semen sample. Fertilization and pregnancy rates (PRs) in relation to sperm parameters and origin of semen sample. Two hundred twenty-seven couples were treated by intracytoplasmic sperm injection resulting in an ongoing pregnancy rate of 37.0% per retrieval (84/227). There were 47 singleton pregnancies (5 of which were vanishing twin pregnancies), 30 twin gestations, 6 triplet pregnancies, and 1 quadruplet pregnancy. The concentration of the total motile spermatozoa present in the ejaculate as well as the origin of the samples influenced the fertilization rate but not the pregnancy outcome. Intracytoplasmic sperm injection can be used successfully to treat couples who have failed IVF or who have too few spermatozoa for conventional methods of in vitro insemination. Sperm parameters do not clearly affect the outcome of this technique.

Evolution of the sperm aster after microinjection of isolated human sperm centrosomes into meiotically mature human oocytes

This study examined the feasibility of isolating and transferring the centrosome-containing region of spermatozoa to mature human oocytes. The findings demonstrate that individual sperm centrosomes can be transferred and are capable of nucleating maternal tubulin to form a well-developed sperm aster in the recipient oocyte. The results are discussed with respect to centrosome function in early human development and applications in clinical in-vitro fertilization in the treatment of certain forms of male factor infertility.

Subzonal insertion of multiple sperm is a treatment for male factor infertility

To determine whether subzonal insemination of multiple sperm is an effective treatment for male factor infertility. Subzonal insemination by micromanipulation of sperm and oocytes for male factor patients. Two hundred eight patients were selected on previous fertilization history and/or semen parameters. They could be assigned to one of three groups: group A had previous IVF failure, group B had a low fertilization rate with previous IVF, and group C had insufficient sperm for IVF. Oocytes were inseminated by subzonal insertion of multiple sperm. Fertilization and pregnancy rates. There have been 208 patients treated through 332 treatment cycles. Of 2,789 oocytes inseminated, 784 oocytes were fertilized (28%) and 516 of these (66%) were monospermic. This represents normal fertilization in 207 cycles (62% of total patient cycles). These 207 cycles produced an average of 2.6 +/- 1.8 embryos. The resultant 487 embryos were either transferred or cryopreserved for future transfer. A total of 42 pregnancies (21% per ET) resulted from 200 ET procedures with 397 embryos. Miscarriages or elective terminations have occurred (11/42 pregnancies, 26% to date) and 21 deliveries have resulted in 26 babies. There are nine ongoing pregnancies. Three of the pregnancies have been from cryopreserved embryos. Group B patients had the highest fertilization rate (23%) but the lowest pregnancy rate (7%). No other significant relationships between patient group and outcome were found. Subzonal insemination of multiple sperm is an effective treatment for some forms of male factor infertility.

Effect of deoxyribonucleic acid protamination on fluorochrome staining and in situ nick-translation of murine and human mature spermatozoa.

A major event in enhancing sperm chromatin stability is the replacement of the histones by protamines during spermiogenesis. In this study, we present results indicating that chromomycin A3 (CMA3) can be used to show protamine deficiency in sperm chromatin. Fixed chromatin of mature mouse spermatozoa showed high fluorescence after treatment with ethidium bromide (EB), but was completely unstained after treatment with CMA3. The same chromatin was found to be highly resistant to in situ nick-translation. In contrast, a substantial fraction of human spermatozoa were positive for CMA3. The accessibility of CMA3 to the DNA of human sperm was eliminated if the slides were previously treated with protamine in situ. This treatment did not affect the accessibility of EB to the chromatin. Individual human sperm samples revealed a substantial frequency of spermatozoa with endogenous nicks, which was found to be the same as the frequency of spermatozoa responding positively to CMA3 staining. Treatment of preparations with protamines prevented the identification of the endogenous nicks. These data as a whole suggest that CMA3 could represent a useful tool for the detection of protamine deficiency in sperm chromatin. Furthermore, confirmation of experiments relating sensitivity to nick translation and positivity to CMA3 may allow an indirect in situ visualization of nicked and partially denatured DNA, which could correlate with certain forms of male factor infertility.

Clinical outcomes of pregnancies achieved by microinsemination by sperm transfer

Micromanipulative techniques such as microinsemination by sperm transfer are evolving as treatment for couples suffering from some forms of male factor infertility where previously donor insemination was the only option. Being a relatively new technology, the numbers of microinsemination by sperm transfer pregnancies that have progressed to term are still small. However, at this time, it would seem that outcome in terms of antenatal complications, gestation length, and birth weight is no different from that seen with conventional IVF. Continuing review of the rate of congenital malformation in microinsemination by sperm transfer progeny seems warranted.

Pentoxifylline stimulates hyperactivation in human spermatozoa

The effects of pentoxifylline on the movement characteristics of human spermatozoa incubated under capacitating conditions were examined using automated digital image analysis. Washed spermatozoa from cryopreserved and fresh normozoospermic, and fresh oligozoospermic semen were incubated in the presence of pentoxifylline (3.6 mM) for 30 min. In each group, pentoxifylline caused an increase in the average lateral head displacement and curvilinear velocity and a decrease in the linearity of progression. This related to a significant increase in the population of spermatozoa developing hyperactivation. The effect was maximal at between 15 and 75 min incubation. No detrimental effect on sperm vitality was demonstrated. It was shown that hyperactivation remained elevated compared with the control after washing pentoxifylline from the suspension. This effect was maintained for 1 h, but became insignificant after 3 h. These data demonstrate that pentoxifylline stimulates the development of hyperactivation in washed human spermatozoa, a phenomenon which may be of value in the treatment of some forms of male factor infertility.

Assisted reproductive technologies for male factor infertility

Experience in the diagnosis and treatment of infertility has led to an increased understanding of the prominent role male factors play in many couples' inability to conceive. While many forms of male factor infertility are amenable to treatment, for some patients there is no corrective therapy available. For this reason, a great deal of attention has been focused on developing technologies for semen processing and sperm utilization in cases of decreased semen quality. One area of research is the development of more sophisticated methods of assessing sperm function, as well as methods of sperm preparation. Progress is also being made in the application of technologies such as intrauterine insemination and in vitro fertilization in the treatment of male factor infertility. Such developments have improved prospects for fertility among patients suffering from decreased semen quality, as well as those suffering from such disorders as ejaculatory failure and congenital vasal agenesis. Current research also offers promise for future applications such as gamete micromanipulation. This technology holds potential for improving fertility even among patients suffering from profound male factor disorders. The following is a summary of recent publications pertaining to the application of these assisted reproductive technologies in the management of male factor infertility.