The definition of Endometriosis Expert Centres.

Endometriosis is a common condition that causes pain and infertility. It can lead to absenteeism and also to multiple surgeries with a consequent risk of impaired fertility, and constitutes a major public health cost. Despite the existence of numerous national and international guidelines, the management of endometriosis remains suboptimal. To address this issue, the French College of Gynaecologists and Obstetricians (CNGOF) and the Society of Gynaecological and Pelvic Surgery (SCGP) convened a committee of experts tasked with defining the criteria for establishing a system of care networks, headed by Expert Centres, covering all of mainland France and its overseas territories. This document sets out the criteria for the designation of Expert Centres. It will serve as a guide for the authorities concerned, to ensure that the means are provided to adequately manage patients with endometriosis.

[Comparison of frozen embryo transfer outcomes at blastocyst stage according to freezing method and type of endometrial preparation]. / Comparaison des issues de transferts d'embryons congelés au stade blastocyste selon la technique de congélation et le type de préparation endométriale.

OBJECTIVE: This study intended to compare frozen embryo transfer (FET) outcomes at blastocyst stage according to freezing methods, slow freezing versus vitrification and according to the type of endometrial preparation. PATIENTS AND METHODS: A total of 172 FET at blastocyst stage (day 5 or 6) were included retrospectively from April, 2007 to December, 2012. The FET outcomes from slow freezing (group 1, n=86) were compared with those from vitrification (group 2, n=86). More particularly, the survival rate after thawing, as well as implantation and pregnancy rates (clinical and ongoing pregnancy rates) were compared respectively between these two groups, after matching on women's age at freezing day, embryo number and embryo development stage for transfer. Furthermore, for each freezing method, FET outcomes were compared according to the type of endometrial preparation, i.e. natural cycle (group N) versus stimulated cycle (group S). RESULTS: The survival rate as well as implantation and clinical pregnancy rates were significantly higher for FET after vitrification compared to FET after slow freezing (97% vs 85%, P<0.0001; 32% vs 20%, P=0.02; 43% vs 28%, P=0.04, respectively). By taking into account the number of transferred embryos for each group, the multiple pregnancy rate was three-fold higher in the group of FET after vitrification compared to the group of FET after slow freezing but not significantly (27.3% vs 8.3%, NS). However, FET outcomes were not affected significantly by the type of endometrial preparation whatever freezing methods. Nevertheless, the early spontaneous abortion (ESA) rate was lower in the case of embryos that were frozen by vitrification and transferred in natural cycle (group N2 vs group S2: 20% vs 47%, NS). DISCUSSION AND CONCLUSION: Our study confirms that the survival rate after thawing at blastocyst stage (day 5 or 6) is significantly improved after freezing by vitrification compared to slow freezing method. Likewise, implantation and clinical pregnancy rates are significantly increased in the case of FET at blastocyst stage when these embryos were frozen by vitrification. The results obtained by vitrification are very satisfactory but are also associated with an increased multiple pregnancy rate. Moreover, FET associated with natural or stimulated cycle does not modify significantly the outcomes of attempts, whatever the freezing method. However, the risk of ESA is reduced in the case of FET with natural cycle and after embryo vitrification.

[Oncofertility program at the Montpellier university hospital 2 years after]. / Programme de préservation de la fertilité féminine au CHRU de Montpellier 2ans après.

OBJECTIVE: Female fertility preservation in the context of cancer management is crucial for patient's health care. The aim of this study was to evaluate the oncofertility practice at our university hospital of Montpellier since 2011. PATIENTS AND METHODS: The evaluation of management of young patients referred to Montpellier University Hospital from September 2011 to September 2013 for oncofertility counselling before cancer treatment. RESULTS: Seventy-one patients were referred to a specialized oncofertility center. Forty-two patients (59.1%) were included in the oncofertility program. Twenty-two patients (31%) were proposed for oocyte vitrification after COS protocol, eight patients (11.3%) for ovarian tissue cryoconservation, seven patients (9.9%) for GnRH injections, three patients (4.2%) ovarian transposition and two patients (2.8%) for embryo cryopreservation. Among the 42 indications of fertility preservation, only 18 will have finally taken place. CONCLUSION: Oncofertility counselling for young patients should now be part of the cancer management. It involves multidisciplinary teams. Further information of both oncologists and patients is needed to improve this new approach in the field of cancer treatments.

Developmental regulated expression of anti- and pro-apoptotic BCL-2 family genes during human early embryonic development.

Apoptotic cell death has been reported in human oocytes and preimplantation embryos under in vivo and in vitro conditions. BCL-2 family proteins comprise both anti- and pro-apoptotic members, which are likely to play a key role in controlling oocyte and early embryo survival. However, very limited data are available on their expression kinetics during human early embryonic development. Using our DNA microarray data, we analyzed the expression pattern of 21 BCL-2 family genes in human mature MII oocytes, day 3 embryos and day 5/6 blastocysts from patients who underwent in vitro fertilization (IVF). Selected genes were further validated by qRT-PCR and their subcellular localization analyzed by immunofluorescence confocal microscopy. Our results suggest a switch from oocyte-inherited BCL-2 family transcripts, such as BCL2L10, to embryo-produced transcripts after embryonic genome activation, including BIK, BCL2L11 and NOXA. Moreover, the pro-apoptotic gene BCL2L13 was constitutively expressed throughout human early embryonic development. Remarkably, day 3 embryos expressed more BCL-2 pro-apoptotic genes than mature MII oocytes and day 5/6 blastocysts, suggesting that embryos at this stage are more prone to apoptosis. This is further supported by an absence of cleaved Caspase-3 in the oocyte and its presence in the embryo. Using a drug that induces apoptosis (gambogic acid), we were able to show activated Caspase-3 in the oocyte in addition to an alteration of BCL2L13 protein localization. Similarly BCL2L13 localization was altered in degenerated oocytes. This study opens new perspectives for understanding the molecular regulation of human oocyte and pre-implantation embryo survival and death.

Altered gene expression profile in cumulus cells of mature MII oocytes from patients with polycystic ovary syndrome.

STUDY QUESTION: Oocyte developmental competence is altered in patients with polycystic ovary syndrome (PCOS); is gene expression in cumulus cells (CCs) from mature metaphase II oocytes of patients with PCOS altered as well? SUMMARY ANSWER: Compared with CCs from non-PCOS patients, the gene expression profile of CCs isolated from mature oocytes of patients with PCOS present alterations that could explain the abnormal folliculogenesis and reduced oocyte competence in such patients. WHAT IS KNOWN ALREADY: Abnormal mRNA expression of several members of the insulin-like growth factor (IGF) family in CCs from PCOS patients was previously reported. Moreover, the whole transcriptome has been investigated in cultured CCs from PCOS patients. STUDY DESIGN, SIZE AND DURATION: This retrospective study included six PCOS patients diagnosed following the Rotterdam Criteria and six non-PCOS patients who all underwent ICSI for male infertility in the assisted reproduction technique (ART) Department of Montpellier University Hospital, between 2009 and 2011. PARTICIPANTS/MATERIALS, SETTING AND METHODS: CCs from PCOS and non-PCOS patients who underwent controlled ovarian stimulation (COS) were isolated mechanically before ICSI. Gene expression profiles were analysed using the microarray technology and the Significance Analysis of Microarray was applied to compare the expression profiles of CCs from PCOS and non-PCOS patients. MAIN RESULTS: The gene expression profile of CCs from patients with PCOS was significantly different from that of CCs from non-PCOS patients. Specifically, CCs from women with PCOS were characterized by abnormal expression of many growth factors, including members of the epidermal growth factor-like (EGFR, EREG and AREG) and IGF-like families (IGF1R, IGF2R, IGF2BP2 and IGFBP2), that are known to play a role in oocyte competence. In addition, mRNA transcripts of factors involved in steroid metabolism, such as CYP11A1, CYP1B1, CYP19A1 and CYP2B7P1, were deregulated in PCOS CCs, and this could explain the abnormal steroidogenesis observed in these women. Functional annotation of the differentially expressed genes suggests that defects in the transforming growth factor ß and estrogen receptors signalling cascades may contribute to the reduced oocyte developmental competence in patients with PCOS. LIMITATIONS AND REASONS FOR CAUTION: Owing to the strict selection criteria (similar age, weight and reasons for ART), this study included a small sample size (six cases and six controls), and thus, further investigations using a large cohort of patients are needed to confirm these results. WIDER IMPLICATIONS OF THE FINDINGS: This study opens a new perspective for understanding the pathogenesis of PCOS. STUDY FUNDING/COMPETING INTERESTS: This work was partially supported by a grant from the Ferring Pharmaceutical. The authors of the study have no competing interests to report. TRIAL REGISTRATION NUMBER: Not applicable.

Neonatal mortality and morbidity in preterm infants born from assisted reproductive technologies.

AIM: Premature birth is frequent in infants conceived with assisted reproductive technologies (ART). We sought to determine whether neonatal outcome in ART preterm infants differs from that of spontaneously conceived (SC) preterm infants. METHODS: Data were prospectively collected in infants born ≤ 32 weeks after ART or SC. We calculated a composite index of severe morbidity (based on occurrences of severe necrotizing enterocolitis, severe intraventricular haemorrhage, periventricular leukomalacia or bronchopulmonary dysplasia). Survival rate without severe morbidity was compared between the two groups. RESULTS: Six hundred and twelve preterm infants were hospitalized in our tertiary care centre: 81 in ART group and 521 in SC group. In the ART group, twin pregnancy (69.1% vs. 15.9%, p < 0.001) and inborn delivery (98.8% vs. 90.0%, p < 0.01) were more frequent. Gestational age (29 vs. 28 weeks, p < 0.05) and birth weight (1100 vs. 1020 g, p < 0.001) were also higher. Survival without severe morbidity was significantly higher in ART infants (76.5% vs. 55.2%, p < 0.001), with the difference mainly observed in infants born ≤ 28 weeks (22.9% vs. 55.7%, p < 0.001). CONCLUSION: Assisted reproductive technologies was not associated with adverse neonatal outcome. Differences in pregnancy and neonatal characteristics probably explain the increased survival without severe morbidity in ART infants.

[Postoperative abdominal adhesions and their prevention in gynaecological surgery: II. How can they be prevented?]. / Adhérences postopératoires et leur prévention en chirurgie gynécologique : II. Comment les prévenir ?

This paper is the second of a two-part publication. The initial paper provided a comprehensive overview of the evidence on adhesions to allow gynaecological surgeons to be best informed on adhesions, their development, impact on patients, health systems and surgical outcomes. There is rising evidence that surgeons can take important steps to reduce the burden of adhesions. In this second paper, we review the various strategies to reduce the impact of adhesions, improve surgical outcomes and provide some practical proposals for action on adhesions. As well as improvements in surgical technique, developments in adhesion-reduction strategies and new agents offer a realistic possibility of reducing adhesion formation and improving outcomes for patients. They should be considered for use particularly in high-risk surgery and in patients with adhesiogenic conditions. Further research into new strategies to prevent adhesions more effectively through an improved surgical environment, new and combination devices and pharmacological agents should be encouraged. Formal recommendations would ensure better prioritisation of adhesion-reduction within the French health system. Patients should also be better informed of the risks of adhesions.

[Postoperative abdominal adhesions and their prevention in gynaecological surgery: I. What should you know?]. / Adhérences postopératoires et leur prévention en chirurgie gynécologique : I. Ce qu'il faut savoir.

Adhesions are the most frequent complications of abdominopelvic surgery, causing important short- and long-term problems, including infertility, chronic pelvic pain and a lifetime risk of small bowel obstruction. They also complicate future surgery with increased morbidity and mortality risk. They pose serious quality of life issues for many patients with associated social and healthcare costs. Despite advances in surgical techniques, including laparoscopy, the healthcare burden of adhesion-related complications has not changed in recent years. Adhesiolysis remains the main treatment although adhesions reform in many patients. The extent of the problem of adhesions has been underestimated by surgeons and the health authorities. There is rising evidence however that surgeons can take important steps to reduce the impact of adhesions. As well as improvements in surgical technique, developments in adhesion-reduction strategies and new agents offer a realistic possibility of reducing adhesion formation and improving outcomes for patients. This paper is the first of a two-part publication providing a comprehensive overview of the evidence on adhesions to allow gynaecological surgeons to be best informed on adhesions, their development, impact on patients, health systems and surgical outcomes. In the second paper we review the various strategies to reduce the impact of adhesions and improve surgical outcomes to assist fellow surgeons in France to consider the adoption of adhesion reduction strategies in their own practice.

[Effects of cigarette smoking on embryo implantation and placentation and analysis of factors interfering with cigarette smoke effects (Part II)]. / Effet du tabagisme sur l'implantation embryonnaire et la placentation précoce et facteurs influençant la toxicité tabagique sur la reproduction (Partie II).

Cigarette smoking is associated with lower fecundity rate, adverse reproductive outcomes and higher risk of IVF failure. Over the last decades, prevalence of smoking among women of reproductive age has increased. The aim of this work was first to focus on the knowledge of the effects of cigarette smoking on reproductive stages and particularly on implantation process and early placentation. Human clinical and experimental studies were analysed in order to find hypothesis and explanations for the effects observed. Then, our second aim was to analyse which factors could influence smoke effects. We observed that smoke compounds induce impairment of endometrial maturation, disturb angiogenesis and trophoblastic invasion. Cigarette compounds also impair uterine and endometrial vascularisation and myometrial relaxation. These effects lead to implantation failure in IVF and higher risk of miscarriage. Many factors influence the effects of cigarette smoke, as smoke behaviour, dose and duration of exposition. Sidestream is also damaging on reproductive function. Prenatal exposure leads to irreversible and deleterious effects on ovarian reserve. These observations need to be confirmed in order to improve health care in women of reproductive age.

[Effects of cigarette smoking on female reproduction: from oocyte to embryo (Part I)]. / Effets du tabagisme sur la reproduction : de l'ovocyte à l'embryon (Partie I).

Cigarette smoking is associated with lower fecundity rate, adverse reproductive outcomes and higher risk of IVF failure. Over the last decades, prevalence of smoking among women of reproductive age has increased. The aim of this work was to focus on the knowledge of the effects of cigarette smoking on all reproductive stages, from oocyte to embryo. For each reproductive functions human clinical and experimental studies were analysed in order to find hypothesis and explanations for effects observed. All reproductive functions are targets of smoke compounds and cigarette smoking impairs ovarian reserve, sexual steroids synthesis, Fallopian tubes functions and embryo development, leading to reduced fecundity. Some of smoke compounds were identified in ovarian tissue, in uterine fluid and in the embryo, suggesting direct toxicity.

Transcriptome analysis reveals dialogues between human trophectoderm and endometrial cells during the implantation period.

BACKGROUND: Crosstalk between human trophectoderm (TE) and endometrial cells during the implantation window is a complex and not well-understood process. The aims of this study were (i) to evaluate the global gene expression profile in TE cells from Day 5 human blastocysts issued from IVF, (ii) to compare these data with the transcriptomic profile of endometrial cells in stimulated cycles for IVF and (iii) to identify potential early dialogues between maternal and embryonic cells during the implantation window. METHODS: Endometrial biopsies (n = 18) from normal responder patients were performed on the day of embryo transfer (Day 5 after human chorionic gonadotrophin administration). TE biopsies from five blastocysts donated for research purposes were mechanically extracted. DNA microarray analysis was carried out to identify the specific gene expression profiles and the biological pathways activated during the implantation window in endometrial and TE cells. RESULTS: Several cytokines (such as PDGFA, placenta growth factor, IGF2BP1 and IGF2BP3) were up-regulated in human TE cells, whereas some of the corresponding receptors (PDGFRA and KDR) were over-expressed in the receptive endometrium, suggesting that these molecules are involved in the early dialogue between blastocyst and maternal endometrial cells. In addition, several adhesion molecules and extracellular matrix proteins (MCAM, ITGAE and LAMA1) were also over-expressed in the TE, while others (ALCAM, CEACAM1, PECAM1, ITGB8 and LAMA2) were restricted to the receptive endometrium. CONCLUSION: The present study shows that several growth factors, cytokines, integrins and adhesion molecules are expressed in the TE and endometrium at the time of implantation. These results could contribute to the understanding of the mechanisms involved in the early dialogue between blastocyst and endometrium during implantation. Such results should be confirmed by further studies.

Effects of cigarette smoking on reproduction.

BACKGROUND Cigarette smoking is associated with lower fecundity rates, adverse reproductive outcomes and a higher risk of IVF failures. Over the last few decades, prevalence of smoking among women of reproductive age has increased. This review focuses on current knowledge of the potential effects of smoke toxicants on all reproductive stages and the consequences of smoke exposure on reproductive functions. METHODS We conducted a systematic review of the scientific literature on the impact of cigarette smoking and smoke constituents on the different stages of reproductive function, including epidemiological, clinical and experimental studies. We attempted to create hypotheses and find explanations for the deleterious effects of cigarette smoke observed in experimental studies. RESULTS Cigarette smoke contains several thousand components (e.g. nicotine, polycyclic aromatic hydrocarbons and cadmium) with diverse effects. Each stage of reproductive function, folliculogenesis, steroidogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow and uterine myometrium is a target for cigarette smoke components. The effects of cigarette smoke are dose-dependent and are influenced by the presence of other toxic substances and hormonal status. Individual sensitivity, dose, time and type of exposure also play a role in the impact of smoke constituents on human fertility. CONCLUSIONS All stages of reproductive functions are targets of cigarette smoke toxicants. Further studies are necessary to better understand the deleterious effects of cigarette smoke compounds on the reproductive system in order to improve health care, help to reduce cigarette smoking and provide a better knowledge of the molecular mechanisms involved in reproductive toxicology.

[Endometriosis and fertility: Results after surgery and Assisted Reproductive Technology (ART)]. / Fertilité des patientes présentant une endométriose traitées par cœlioscopie et AMP.

OBJECTIVE: To evaluate fertility outcomes after laparoscopic and ART management of endometriosis in an infertile population. PATIENTS AND METHODS: Retrospective analysis including 79 infertile patients treated by laparoscopic surgery. Fertility was studied in relation to pregnancy's mode (spontaneous or ART) and to endometriosis stages (rAFS). RESULTS: After laparoscopy, 8.9% of patients had a spontaneous pregnancy. IIU led to a cumulative rate of pregnant women of 21.5%. Then after laparoscopy, IIU and IVF, 68.4% of patients were pregnant. The average delay was 460 days between laparoscopy and spontaneous pregnancy, 271 days between surgery and IIU pregnancy and 600 days between surgery and IVF pregnancy. Among women with stages I-II endometriosis (62 cases), 11.3% patients obtained a spontaneous pregnancy, the cumulative rate of pregnant women after laparoscopy and IIU was 25,8%. After laparoscopy, IIU and IVF, 66.1% of patients were pregnant. The average post-surgical time to spontaneous pregnancy was 460 days. The average delay between surgery and IIU pregnancy was 279 days and 589 days between surgery and IVF pregnancy. In case of stages III-IV (17 patients), 76.4% of pregnancies were obtained. No spontaneous pregnancy was observed. 94.1% of patients were treated with IVF, leading to a global rate of pregnancy of 70.5%. The average delay between surgery and IVF pregnancy was 563 days. CONCLUSIONS: With a combination of surgery and ART, two-third of patients were pregnant with an average time between surgery and pregnancy of less than two years. This combination (surgery and ART) increases the chances of becoming pregnant. At the moment, the delay between surgery and ART needs to be established.

Recommendations for investigation of hyperandrogenism.

1. Total testosterone assay is recommended as the first-line approach. 2. Radioimmunological assay following prior treatment of the sample (extraction or extraction + chromatography) is the recommended method pending wider experience with mass spectrometry. 3. Where testosterone is twice the upper limit of normal, it is recommended that DHEAS assay be performed. DHEAS is primarily of cortico-adrenal origin in women. Thus, a DHEAS level over 600 mg/dl indicates a diagnosis of androgen-secreting adrenal cortical adenoma.. If DHEAS is normal, the diagnosis could be either ovarian hyperthecosis, normally associated with insulin resistance, or androgen-secreting ovarian tumour. 4. More rarely, elevated testosterone is associated with a marked elevation of SHBG possibly as the result of use of medication having an estrogenic effect (tamoxifen, raloxifene, Op'DDD), or of hyperthyroidism or liver disease. 5. Normal testosterone levels in patients with clear clinical symptoms of hyperandrogenism (hirsutism, seborrhoeic acne) must be interpreted with care. SHBG is normally reduced in the event of overweight, metabolic syndrome or familial history of diabetes.

[Laparoscopic cervico-isthmic cerclage evaluation]. / Evaluation du cerclage isthmique par voie coelioscopique.

OBJECTIVE: The transabdominal cervico-isthmic cerclage could to be proposed in case of failure of vaginal cerclage, 2nd trimester fetal losses and cervical defects. The efficiency of the laparoscopic approach, more recently described, has to be demonstrated for the prevention of obstetrical accident. PATIENTS AND METHODS: This study is a retrospective monocentric evaluation of 14 laparoscopic cervico-isthmic cerclages performed with Benson modified technique before pregnancy between 2005 and 2007. Previous obstetrical accidents, etiology of cervical incompetence and patient outcome after cerclage were compared. RESULTS: Median age of the patients was 33.5 years; 93% had previous fetal losses or preterm delivery and 42.9% had failure of Mac Donald cerclages. The indication of laparoscopic cervico-isthmic cerclage was Mac Donald cerclage failure (six cases), and eight cases of anatomic incompatibility of Mac Donald cerclage. Mean duration of laparoscopic cervico-isthmic cerclage was 45 minutes. All patients were hospitalized on an outpatient basis. No operative complication was reported. Six women were pregnant after cerclage: five deliveries by caesarean section at term, and one first trimester foetal loss. DISCUSSION AND CONCLUSION: The cervico-isthmic cerclage can be easily performed by laparoscopy. The indications are strictly the same as cervico-isthmic cerclages by laparotomy. Increasing the number of term deliveries and the obstetrical outcome of these patients, the efficiency of the cervico-isthmic cerclage by laparoscopy is demonstrated.

Identification of new biomarkers of human endometrial receptivity in the natural cycle.

BACKGROUND: Identification of new markers assessing endometrial receptivity may help in improving the clinical outcome of IVF. This study aimed at identifying genes expressed in human endometrium during the implantation window that could be used as such markers. METHODS: A series of normoresponder patients (n = 31) underwent endometrial biopsies (n = 62, 2 per patient) during the early secretory phase, 2 days after the LH surge (LH + 2) and the mid-secretory phase (LH + 7) of the same natural cycle that preceded a new ICSI attempt for male infertility factor. Samples were analyzed using DNA microarrays and gene expression profiles at the time of the implantation window were computed. Systems biology analysis allowed the identification of biological pathways that were over-represented in this signature. A new approach for class prediction applied to microarray experiments was then used to identify biomarkers putatively involved in endometrial receptiveness. RESULTS: Five genes expressed during the implantation window were all up-regulated in the LH + 7 samples compared with LH + 2 [laminin beta3 (P = 0.002), microfibril-associated protein 5 (P = 0.009), angiopoietin-like 1 (P = 0.005), endocrine gland-derived vascular endothelial growth factor (P = 0.049) and nuclear localized factor 2 (P = 0.007)]. Increased expression was validated by quantitative RT-PCR. CONCLUSIONS: Five genes have been identified for the first time as being up-regulated during the implantation window and are proposed as new biomarkers for exploration of endometrial receptiveness. As the endometrial biopsy procedure can be performed during a natural cycle, it would be worth testing this approach as a novel strategy in patients with poor implantation after IVF or ICSI.

Tumor necrosis factor-alpha -308 polymorphism in infertile men with altered sperm production or motility.

BACKGROUND: One of the most well-documented cytokines suspected as a hazard to male fertility is tumor necrosis factor-alpha (TNFalpha). Genetic factors such as single-nucleotide polymorphisms (SNPs) in the TNF gene cluster impact TNFalpha levels. Our objective was to establish the potential involvement of -308 TNF SNP in male infertility risk. METHODS: In 684 infertile male patients undergoing an intracytoplasmic sperm injection procedure, we used allele-specific polymerase chain reaction (PCR) and PCR-RFLP to investigate the distribution of the guanine (G)-to-adenosine (A) substitution at position -308 in the promoter region of the TNFalpha gene. RESULTS: An increased frequency of the -308 TNFalpha A allele was found in patients with low sperm count of testicular origin [P = 0.002; odds ratio (OR) = 2.93] or with normal production count but altered sperm motility (P = 0.003; OR = 2.32), compared with a patient group with normal sperm count and quality (morphology and motility). In patients with low sperm count exhibiting TNFalpha A allele, compared with those with G allele, an alteration in hormonal balance was observed with increased inhibin B levels and subsequent reduced FSH plasma levels, leading to an FSH/inhibin B ratio roughly half as high (from 0.07 +/- 0.01 in TNFA versus 0.13 +/- 0.02 in TNFG allele groups, P < 0.0001). CONCLUSION: As the -308 TNFalpha A allele has been associated with an increased expression/production of TNFalpha, the potential use of therapies based on inhibition of TNFalpha activities could represent possible therapeutic opportunities for patients with low sperm count (i.e. primary testicular dysfunction) or with altered sperm motility.