Varicocele--the most common cause of male factor infertility?

Varicocele is often cited as the most common cause of male factor infertility. Arguments in support of this statement include reports of increased prevalence of varicocele in populations of infertile men compared with fertile or otherwise unselected men, association of varicocele with abnormal semen parameters, and improvements in semen parameters and/or pregnancy rates after varicocele repair. Logically, there would appear to be three possibilities regarding the relationship between varicocele and fertility: (i) varicocele has no association with or effect on male fertility; (ii) varicocele may be associated with, but is not the cause of, male subfertility; and (iii) varicocele is a direct cause of male subfertility. In the following, we review evidence from the literature for and against these three possibilities: at the current time, available evidence appears inadequate to confirm or deny any of these three possibilities. Since the ultimate goal of infertile couples is to conceive, it seem logical that future varicocele research should focus primarily on adequately powered, controlled clinical trials in well-characterized infertile couples, randomized to intervention or appropriate controlled observation, with pregnancy as the primary outcome.     

The best donor.

Oocyte donation has become a common treatment modality for a large spectrum of infertility conditions. The purpose of this study was to assess the success rate of a shared egg donation programme, and to define the profile of a successful 'donor-recipient' couple in view of the limitations imposed by the shared programme. The results of all consecutive cycles of egg donation from 1st January 1995 to 31st December 1996 were analysed. A total of 383 donor cycles were matched with 946 recipient cycles; clinical pregnancy rates were 23. 5 and 16.7% respectively. With the exception of endometriosis, which significantly reduced the pregnancy rate in both groups, similar pregnancy rates were obtained in both groups for all the other infertility aetiologies of the donors. The donor's age had no impact on pregnancy rate of the recipient, but pregnancy rate was significantly decreased in donors >35 years. Recipients >50 years had significantly reduced pregnancy rates and those >45 years a significantly increased abortion rate. Recipients with severe male factor infertility, who had intracytoplasmic sperm injection treatment, showed pregnancy rates equivalent to those recipients who had regular in-vitro fertilization. We conclude that in a shared egg donation programme, the recipients' pregnancy rate and outcome are dependent only on the donors' infertility aetiologies and on recipients' ages.     

The relationship of abnormal semen parameters to male fertility

To what extent do standard semen parameters reflect male fertility? A review of many studies over the last 35 years relating pregnancy rate to sperm counts in 'fertile' and 'infertile' couples indicates that standard semen parameters, though much maligned of late, are useful in evaluating the degree of 'male factor' in an infertile couple. However, 'male factor' is quite compatible with fertility in a couple if the wife is very fertile. Oligoasthenozoospermia is, unfortunately, for the most part, an untreatable condition. Yet, vigorous treatment of the wife may still result in pregnancy despite very poor semen quality. Higher sperm counts in an infertile couple are associated with higher pregnancy rates. But in the majority of infertile couples in whom the sperm count is poor, female factors also exist that prevent conception. If the wife were very fertile, she would have become pregnant despite her husband's oligozoospermia, and they would never have seen a physician for infertility. Thus, pregnancy can be achieved with very low sperm counts either by treatment of the wife, IVF, GIFT or ZIFT procedures.     

Demonstration of Chlamydia trachomatis IgG antibodies in the male partner of the infertile couple is correlated with a reduced likelihood of achieving pregnancy

BACKGROUND: The objective of this study was to determine the prevalence of Chlamydia trachomatis among both men and women seeking help at an infertility clinic, and to prospectively follow the effect of previous infection on pregnancy rates and pregnancy outcome after a long follow-up period (mean 37 months). METHODS: A total of 244 infertile couples was tested for C. trachomatis IgG antibodies, and IgG(+) couples were also tested for C. trachomatis DNA by PCR in a first-void urine sample. Study parameters were serology, PCR results, clinical diagnoses, treatments, pregnancy rates and pregnancy outcome. As controls, age-matched and spontaneously pregnant women were also tested with serology. RESULTS: The prevalence of IgG antibodies was 24.2, 20.1 and 15.6% among infertile women, infertile men and control women respectively. The prevalence of C. trachomatis DNA was 6.8 and 7.1% among tested women and men respectively. The presence of C. trachomatis IgG antibodies in women was related to tubal factor infertility (TFI) (P = 0.002). Decreased pregnancy rates were seen in couples where the man was IgG(+) (P = 0.005) with no relationship to TFI. Among women who achieved pregnancy, there was no difference in pregnancy outcome between IgG(+) or negative couples. CONCLUSIONS: C. trachomatis IgG antibodies in the man of the infertile couple was related to decreased pregnancy rates and to the presence of IgG antibodies in the woman. There was a high prevalence of asymptomatic persistent infections among infertile couples.     

Intrauterine insemination: a systematic review on determinants of success

Intrauterine insemination (IUI) is a frequently indicated therapeutic modality in infertility. Here, a systematic review of the literature was performed to examine the current status of clinical and laboratory methodologies used in IUI and the impact of female and male factors on pregnancy success. Emphasis was centred in questioning the following: (i) the value of IUI against timed intercourse; (ii) IUI application with or without controlled ovarian hyperstimulation; (iii) timing and frequency of IUI; and (iv) impact of various parameters (male/female) on the prediction of pregnancy outcome. The odds of multiple pregnancy occurrence and its risk factors, as well as the cost-effectiveness of IUI treatment compared with more complex assisted reproductive technologies are discussed. A computerized literature search was performed including Medline and the Cochrane library, as well as a crossover search from retrieved papers. It is concluded that although IUI is a successful contemporary treatment for appropriately selected cases of female and/or male infertility, further research is needed through well-designed studies to improve the methodologies currently utilized. Importantly, the clinical management of the infertile couple should be performed in an expedited manner taking into consideration the age of the woman, the presence of multifactorial infertility and cost-effectiveness of the available treatment alternatives.     

Why do infertile males use psychological couple counselling?

The purpose of the present study was to identify characteristics of male patients that could be relevant for the uptake of psychological couple counselling for infertility. Therefore, 94 male patients who participated in psychological couple counselling were compared to 134 unselected infertility patients who attended an andrological clinic. Counselling users showed higher scores for depression and anxiety as well as a higher number of impaired sperm parameters. Multivariate analysis revealed that beyond the level of depression the number of impaired sperm parameters delivered additional information about the probability of a patient using counselling. For interpretation of these results the former research was broadly reviewed. It is suggested that an increased level of distress, the feeling of being responsible for infertility and few marital difficulties are relevant for the usage of couple counselling by male infertility patients. Practical consequences are discussed.     

Recurrent heterotopic pregnancy after repeated in-vitro fertilization treatment

We report a rare clinical case of recurrent heterotopic pregnancy in the same patient following in-vitro fertilization treatments. A 27 year old woman, who suffered from infertility for the last 4 years due to male factor, was being treated by intracytoplasmic sperm injection which resulted in two episodes of combined intrauterine and tubal pregnancy, in a 1 year period. The first ended in emergency salpingectomy by laparotomy and missed intrauterine abortion. The second was managed by laparoscopic salpingectomy and the synchronous pregnancy ended in the delivery of twins. The possibility of heterotopic pregnancy and recurrent heterotopic pregnancy, though rare, should be considered by every gynaecologist, especially those who use infertility treatment on patients.      

IVF pregnancy after induction of an ovulatory endogenous gonadotrophin surge using an LHRH agonist nasal spray

A successful human twin IVF pregnancy is reported after using a single 50 micrograms dose of LHRH agonist nasal spray (Buserelin) to induce an ovulatory endogenous gonadotrophin surge 34 h prior to oocyte collection. The couple had 10 years of primary male factor infertility, associated with significant anti-sperm antibodies. The clinical features and endocrine profile are presented.     

Failure of pregnancy after intracytoplasmic sperm injection with decapitated spermatozoa: case report.

The case of a couple with a history of long standing primary infertility is reported in which the man presented with a decapitated sperm defect. The woman had a normal history and presented with normal clinical characteristics. The couple underwent one unsuccessful conventional in-vitro fertilization (IVF). Subsequently, embryos were obtained and transferred after assisted fertilization attempts: in all, three subzonal inseminations and four intracytoplasmic sperm injections. A total of 49 mature oocytes was injected in both studies, 25 embryos obtained and 20 embryos transferred, three of them after freezing and thawing. Despite the good embryo morphology, implantation was unsuccessful and no pregnancy occurred. The failure of implantation may have resulted from an arrest in early embryonic development related to the sperm anomaly. One hypothesis is that transferred embryos may carry a chromosomal imbalance that prevents them from progressing to the blastocyst stage. Nevertheless, we cannot exclude the possibility that the woman is responsible for the implantation failure. Co-culture associated with a further attempt could provide information regarding the ability of embryos to progress to the blastocyst stage and implant.     

Pregnancy after direct intraperitoneal insemination of spermatozoa from a man with severe infertility, after unsuccessful application of other methods of assisted fertilization

Direct intraperitoneal insemination (DIPI) is one of the least invasive strategies of assisted reproduction. Unexplained infertility and male sub-fertility are the major indications for DIPI. It is otherwise well known that assisted procreation gives poor results in severe male infertility. This is a report of a pregnancy that occurred as a result of a direct intraperitoneal insemination of prepared spermatozoa characterized by a particularly severe astheno-teratozoospermia in a couple unsuccessfully treated with other, more invasive methods of assisted fertilization.     

Varicocele as a progressive lesion: positive effect of varicocele repair

Varicoceles are the leading correctable cause of infertility in men who present to an infertility clinic for evaluation. Consequently, the surgical correction of a varicocele, known as a varicocelectomy, is the most commonly performed operation for the treatment of male infertility. The current data suggest that an individual with a varicocele, even with a previously normal semen analysis or documentation of previous fertility, is at risk for subsequent loss of testicular function and infertility. Many of these patients will need to be treated because there is convincing evidence that a varicocele may have a progressive toxic effect on the testes that may ultimately result in irreversible infertility if left untreated. Identifying those individuals with varicoceles that will ultimately cause fertility impairment is still beyond our current clinical capabilities. Current investigative modalities, e.g. semen analysis, testicular measurement, serum gonadotrophin determination, gonadotrophin-releasing hormone (GnRH) stimulation test, and testis biopsy analysis, may be employed to detect early changes in testicular physiology produced by a varicocele.     

Assessment of the cause of infertility

The different causes of infertility and evaluation of the infertile couple are reviewed in this paper. Forty to 50 percent of cases are due to male factors, and special emphasis is placed in describing techniques to diagnosis this type of infertility. Five to ten percent of infertile couples have infertility of unknown etiology even after a complete, appropriate evaluation. Special instruction in how to diagnose and treat these types of patients is described. A step by step evaluation of peritoneal factors, ovulation factors, and male and cervical mucus interaction is presented for the clinicians' use.     

Pregnancies after ICSI using sperm with abnormal head-tail junction from two brothers: case report

We report ICSI pregnancies in two couples with a history of long standing primary infertility in which the sperm of the male partner were either acephalic or had abnormal head-midpiece attachments. The two couples, in which the men are brothers, underwent ICSI. Sperm were analysed by transmission electron microscopy and immunocytochemistry with an anti-MPM2 monoclonal antibody. The first couple underwent two ICSI cycles, each consisting of the injection of two mature oocytes and the transfer of two embryos. A successful pregnancy occurred after the second transfer and led to the birth to a healthy girl. The second couple underwent three ICSI cycles, each consisting of the injection of 18 oocytes and the transfer of two embryos; the last of these led to a triple ongoing pregnancy which included two identical twins. Caesarean section led to the birth of three fetal-growth restricted children. This case report demonstrates that ongoing pregnancies can be achieved in cases of abnormal development of the head-neck attachment. The genetic origin of this syndrome is generally accepted, but the phenotypic heterogeneity observed by light and electron microscopy among published cases suggests that there are a variety of genetic causes of this syndrome.     

Leiomyomas of the bilateral tunica albuginea of testes: a case report

Leiomyoma of the bilateral testicular tunica albuginea is extremely rare. To our knowledge, there are only 3 definitely reported cases. This is the first report of bilateral testicular tunica albuginea leiomyomas as a potential cause of male infertility. Herein, we report a case of a 47-year-old man who presented with painless bilateral testicular masses for more than 30 years, besides he also suffered from unexplained infertility. The complete resection of the tumors was performed. The final pathological diagnosis was leiomyomas of the bilateral tunica albuginea. Postoperatively, the patient underwent testicular biopsy. Histopathology confirmed moderate atrophy of bilateral testes, and the number of spermatogenic cells in the seminiferous tubules were significantly decreased. In this case, bilateral testicular dysplasia is the root reason for the patient’s infertility. Thus, despite the benign nature of bilateral testicular tunica albuginea leiomyomas, they may cause bilateral testicular hypoplasia and infertility in men. In the case of men with fertility requirements, early local mass excision is often necessary.     

Recovery of spermatogenesis and successful conception after bone marrow transplant for acute leukaemia: case report

A case is presented of a young adult male diagnosed with acute myeloid leukaemia who was treated with busulphan and cyclophosphamide, but not total body irradiation, with subsequent bone marrow transplantation. After surviving for 5 years, he and his wife experienced a period of infertility. Interestingly, the problem was found to be with the female partner and the man's sperm evaluation seemed normal. A successful pregnancy ensued following the surgical removal of a large endometrioma and treating a luteal phase deficiency. Though this may be the fifth case of proven parentage in cases of bone marrow conditioning and bone marrow transplantation in a male for control of leukaemia, we believe it is the first documented case showing a normal semen analysis despite treatment. Further studies are needed to see if chemical conditioning with busulphan and cyclophosphamide preserve the chances of sperm production better than total body irradiation.     

Is the CAG repeat of mitochondrial DNA polymerase gamma (POLG) associated with male infertility? A multi-centre French study

BACKGROUND: Recent data emphasized the implication of polymerase gamma (POLG) CAG repeats in infertility, making it a very attractive gene for study. A comparison of POLG CAG repeats in infertile and fertile men showed a clear association between the absence of the usual 10-CAG allele and male infertility, excluding azoospermia. It has also been suggested that the POLG gene polymorphism should be considered as a possible contributing factor in unexplained couple infertility where semen parameters are normal. In this study, we investigated the POLG CAG repeats, in a well-defined population of patients with severe male factor infertility. METHODS: We conducted a large study of POLG CAG repeats in 433 infertile and 91 fertile, normozoospermic and healthy males. In all subjects, phenotypic data, including semen parameters, hormonal status and clinical profiles, were available. RESULTS: Thirteen 'homozygous mutants' (3%) were found among the 433 idiopathic infertile patients. The follow-up of the 13 'homozygous mutant' resulted in pregnancy for more than half of the couples, through assisted reproductive techniques or even spontaneously. In addition, one 'homozygous mutant' was identified in 91 fertile men (1.1%) CONCLUSION: Under our conditions, our study does not confirm any relationship between the polymorphic CAG repeat in the POLG gene and male infertility.     

Guidelines for the appropriate use of genetic tests in infertile couples

Research on genetic causes of male and female infertility rapidly expanded in the last years, following the development of in vitro fertilising techniques. Genetic tests are now available to explore the cause of the infertility and assess the risk of a given couple to transmit its genetic characteristics. This allows at-risk couples to take an informed decision when electing for a medically assisted reproduction. It also allows the professionals to offer a prenatal diagnosis when appropriate. Thus, the genetic work-up of the infertile couple has become good practice for an appropriate diagnosis, treatment and prognostic assessment. The lack of national or international rules for the genetic approach to the infertile couple, prompted the Italian community of professionals in the field of reproductive medicine to join and set up guidelines for the genetic diagnosis of male and female infertility. The group of clinical and research experts is representative of 12 national scientific societies and was supported by external experts from four international societies. We examine the clinically relevant genetic causes of male and female infertility and suggest the category of patients for which each genetic test is recommended or optional, both for an accurate diagnosis and prior to ART.     

First recorded pregnancy and normal birth after ICSI using electrophoretically isolated spermatozoa

BACKGROUND: DNA damage in the male germ line is associated with poor fertilization and cleavage rates, impaired embryo quality and early pregnancy loss. Given these associations, embryologists are keen to develop techniques that will allow the selection of viable spermatozoa exhibiting low levels of DNA damage for assisted conception purposes. METHODS: In this article, we describe a novel electrophoretic approach for the rapid isolation of cells possessing little DNA damage. The limits of the method were examined using cryostored and snap-frozen semen samples as well as testicular biopsy material. In addition, clinical utility was demonstrated in a case study involving treatment of a patient exhibiting persistently high levels of DNA damage in his spermatozoa. RESULTS: From a range of difficult starting materials (biopsies, cryostored semen and snap-frozen sperm suspensions), the electrophoretic system rapidly isolated populations of motile, viable, morphologically normal spermatozoa exhibiting high levels of DNA integrity. Clinical application in a couple suffering from long-term infertility associated with extensive DNA damage in the male germ line led to the first human pregnancy following such electrophoretic sperm isolation. CONCLUSIONS: The electrophoretic procedure holds promise as a convenient method for the rapid preparation of high-quality spermatozoa for assisted conception purposes.     

Risk factors for female and male infertility: results of a case-control study.

In order to evaluate male and female risk factors for infertility in a case-control study, we have compared all couples in a French administrative region consulting for primary or secondary infertility (of more than one year's duration) with couples in which the woman had given birth during the year of the study. For any one couple, a history of varicocele, male genital infections or testis damage multiplies the risk of primary infertility by a factor of 28, 3 and 4 respectively, and previous female infections (salpingitis) multiply the risk by 45. Similarly, a history of ectopic pregnancy, sexually transmitted diseases or salpingitis multiplies the risk of secondary infertility by a factor of 5, 4 and 7 respectively, and a history of varicocele multiplies this risk by 4.