Motivations and personality characteristics of candidate sperm and oocyte donors according to parenthood status: a national study from the French CECOS network.

STUDY QUESTION: In a non-commercial national gamete donation programme, do the motivations and personality characteristics of candidate sperm and oocyte donors differ according to their parenthood status? SUMMARY ANSWER: Moderate differences exist between non-parent and parent candidate donors in motivations for gamete donation and representations as well as in personality characteristics. WHAT IS KNOWN ALREADY: Several studies have analysed the motivations and experiences of oocyte or sperm donors, but mainly in countries where gamete donation is a commercial transaction, and very few studies have reported results of personality traits using personality inventory tests. No study has specifically investigated the motivations and personality characteristics of candidate gamete donors according to parenthood status. STUDY DESIGN SIZE DURATION: A prospective study was carried out including 1021 candidate donors from 21 centres (in university hospitals) of the national sperm and egg banking network in France between November 2016 and December 2018. PARTICIPANTS/MATERIALS SETTING METHODS: In total, 1021 candidate gamete donors were included in the study. During their first visit, male (n = 488) and female candidate donors (n = 533) completed a questionnaire on sociodemographic characteristics, their motivations for donation and their representations of donation, infertility and family. Secondly, a NEO Personality Inventory (NEO-PI-R) exploring the Big Five personality traits was completed online. Results were compared between parent and non-parent candidate donors. MAIN RESULTS AND THE ROLE OF CHANCE: Altruistic values were the principal motive for donation irrespective of parenthood status. Reassurance about their fertility or preservation of sperm for future use was more often reported in non-parent than in parent candidate donors. With regard to representation of gamete donation or of the family, independently of their parenthood status, candidate donors more frequently selected social rather than biological representations. Mean personality characteristics were in the normal range. Non-parent candidate donors had higher scores on openness and depression than parents, while parent candidate donors appeared more social than non-parents. LIMITATIONS REASONS FOR CAUTION: The personality characteristics inventory was not completed by all candidate donors included in the study. However, family status did not differ between the two groups (NEO-PI-R completed (n = 525) or not), while the group who completed the NEO-PI-R had a higher educational level. This national study was performed in a country where gamete donation is subject to strict legislation. WIDER IMPLICATIONS OF THE FINDINGS: In a global context where reproductive medicine is commercialized and gamete donor resources are limited, this study found that altruism and social representations of gamete donation and family are the main motivations for gamete donation in a country which prohibits financial incentive. These findings are relevant for health policy and for gamete donation information campaigns. STUDY FUNDING/COMPETING INTERESTS: Grant from the Agence de la Biomédecine, France. The authors have nothing to disclose related to this study. TRIAL REGISTRATION NUMBER: N/A.

Decrease of spermatozoa with an unbalanced chromosome content after cell sorting in men carrying a structural chromosomal abnormality.

BACKGROUND: We showed that in men with a constitutional chromosomal abnormality, DNA fragmentation was significantly higher in chromosomally unbalanced spermatozoa than in spermatozoa with a normal or balanced chromosomal content. These results could be explained by a phenomenon already described in infertile men: abortive apoptosis. OBJECTIVES: To determine whether magnetic-activated cell separation could select spermatozoa with lower levels of DNA fragmentation and unbalanced chromosome content in men carrying a structural chromosomal abnormality. MATERIALS AND METHODS: The spermatozoa of ten males with a chromosomal rearrangement were separated into two populations using magnetic-activated cell separation (annexin V (-) and annexin V (+) fractions), in order to study meiotic segregation by fluorescence in situ hybridization, the percentage of spermatozoa with an externalization of phosphatidylserine by annexin V staining and DNA fragmentation by TdT-mediated dUTP nick-end labeling on the whole ejaculate and on selected spermatozoa in the same patient. RESULTS: For all patients, the percentage of spermatozoa with externalization of phosphatidylserine decreased in the annexin V (-) fraction and increased in the annexin V (+) fraction as compared to the frozen-thawed semen sample. The rates of DNA fragmentation were statistically much lower in the annexin V (-) fraction when compared to the rate before magnetic-activated cell separation for all but one patient. Conversely, we observed a statistically significantly higher rate of DNA fragmentation in the annexin V (+) fraction for six patients. After magnetic-activated cell separation, there was a significant increase of normal/balanced spermatozoa in the fraction of annexin V (-) for all patients. Conversely, we observed a significant decrease in the fraction of annexin V (+) for seven patients. DISCUSSION AND CONCLUSIONS: Magnetic-activated cell separation is a promising tool for increasing the selection of healthy spermatozoa, with a decrease in the number of spermatozoa with externalization of phosphatidylserine, DNA fragmentation, and chromosome unbalance, for use in assisted reproductive technologies such as intracytoplasmic sperm injection for males with a chromosomal structural abnormality.

People living with HIV and procreation: 30 years of progress from prohibition to freedom?

The emergence of human immunodeficiency virus (HIV) infection in the 1980s drastically changed the prospects of conceiving a child for the man or woman infected with the virus. Advances in treatment then made it possible to envisage pregnancy while decreasing the risk of transmission to the child when the mother was infected. For couples where one partner was HIV-positive and who desired a child, recourse to medical help, notably medically assisted procreation, was discouraged, and very few centres offered such assistance in the 1980s and 1990s. Improved knowledge of viral excretion in the genital tracts, together with more effective treatment, made it possible to envisage medically assisted procreation for these couples, allowing them to have a child while at the same time likely reducing the risk of transmitting HIV to their partner. Several programmes have demonstrated their effectiveness in this domain. Owing to continually increasing knowledge over the past decade, natural conception can now be proposed. Couples where one or both partners are HIV-positive may opt for medically assisted procreation or natural reproduction. Specialists in reproductive medicine and HIV specialists need to provide couples with objective information allowing them to achieve near-optimal conditions that minimize HIV transmission risk. Couples will then be able to choose freely the mode of procreation most appropriate for them.

Sperm freezing to address the risk of azoospermia on the day of ICSI.

STUDY QUESTION: In which cases is freezing of ejaculated sperm indicated before ICSI? SUMMARY ANSWER: Sperm freezing should be performed only when out of two analyses at least one total sperm count in the ejaculate is lower than 10(6). WHAT IS KNOWN ALREADY: Due to variations in individual sperm parameters, in cases of severe oligozoospermia there is a risk of absence of spermatozoa on the day of ICSI, leading to cancellation of the attempt. Sperm freezing can avoid this problem but little is known of the parameters governing the decision to freeze sperm or not. STUDY DESIGN, SIZE, DURATION: This retrospective study included 247 men who underwent sperm cryopreservation to prevent the risk of azoospermia on the day of ICSI, from 2000 to 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Receiver operating characteristic curve analysis was used to define the threshold value. The lowest total sperm count per ejaculate was studied as a predictive factor for the use of frozen sperm in a total of 593 ICSI attempts. Moreover, 2003 patients who had at least 4 semen analyses for andrological diagnosis have been studied to evaluate the reproducibility of sperm count. To evaluate the psychological impact of sperm freezing, a questionnaire was administered to 84 men who attended for sperm cryopreservation between June and December 2014. The cost of sperm freezing was analysed according to the French prices. MAIN RESULTS AND THE ROLE OF CHANCE: When at least one total sperm count was <10(5) the risk of azoospermia in at least one ICSI attempt was 52% (34/66) versus 3% (5/181) when all counts were ≥10(5) (P < 0.0001). However, the study of the reproducibility of pre-ICSI semen analyses has shown wide variations among ejaculates, and therefore sperm freezing is recommended when one analysis from at least two, showed a sperm count <10(6). Such a policy could allow a saving of about €70 000 by avoiding unnecessary sperm freezings. The psychological impact of sperm freezing was good since >70% of men had positive feelings about this technique. LIMITATIONS, REASONS FOR CAUTION: This was a fairly short-term study and preservation of future fertility was not assessed. It appeared impossible to find a threshold that would predict the risk of azoospermia with 100% accuracy. Therefore there is still a risk of absence of spermatozoa on the day of ICSI despite a good negative predictive value when no total sperm count was lower than 10(5). WIDER IMPLICATIONS OF THE FINDINGS: These data suggest that sperm freezing should be proposed when total sperm count is lower than 10(6) to avoid cancellation of the ICSI attempt due to azoospermia.

[Reproductive options for people living with HIV: 2013 guidelines from the French expert working group]. / Désir d'enfant chez les personnes vivant avec le VIH : nouvelles recommandations 2013 du groupe d'experts français.

The desire for children is a legitimate aspiration that should be part of multidisciplinary care for all men, women or couples living with HIV. The use of effective antiretroviral therapy has revolutionized the prevention of sexual, as well as mother-to-child HIV transmission. When the HIV plasma viral load is undetectable on long-term antiretroviral therapy, the risk of mother-to-child transmission is <1% and the risk of heterosexual HIV transmission without condom use in a stable relationship is very low (estimated at less than 1/10,000) in the absence of inflammation of the genital tract. In a man with a long-term undetectable viral load, viral shedding in semen is uncommon, but may occur persistently or intermittently. The same appears true of viral shedding in the vaginal tract of women. Reproductive options are: natural conception, self-insemination when the woman is HIV-infected, assisted reproduction. Natural conception is now considered to be an acceptable option when the conditions are met, after exploring four aspects: (1) virological (viral load undetectable sustained for at least 6 months on therapy), (2) genital (absence of genital infections or lesions), (3) fertility (after appropriate evaluation) and (4) detecting the ovulation period to limit intercourse without condoms. Assisted reproduction has two objectives in the context of HIV, to allow the couple to conceive without abandoning condom use and/or to treat infertility.

[HIV and pregnancy: 2013 guidelines from the French expert working group]. / Infection par le VIH et grossesse: nouvelles recommandations 2013 du groupe d'experts français.

With effective antiretroviral therapy, the risk of mother to child transmission (MTCT) is now under 1%. The 2013 French guidelines emphasize early antiretroviral lifelong antiretroviral therapy. Thus, the current trend for women living with HIV is to take antiretroviral therapy before, during and after their pregnancies. A major issue today is the choice of antiretroviral drugs, to maximize the benefits and minimize the risks of fetal exposure. This requires interdisciplinary care. The use of effective therapies permits gradual but profound changes in obstetric practice. When maternal plasma viral load is controlled (<50 copies/ml), obstetrical care can be more similar to standards in HIV-negative women. Prophylactic cesarean section is recommended when the viral load in late pregnancy is above 400 copies/mL. Intravenous zidovudine during labor is recommended only if the last maternal viral load is>400 copies/mL or in case of complications such as preterm delivery, bleeding or chorio-amnionitis during labor. In case of premature rupture of membranes before 34 weeks, a multidisciplinary decision should be made, based on gestational age and control of maternal viral load; if the woman is under antiretroviral therapy and especially if her viral load is undetectable, steroids and antibiotics should be offered and pregnancy can be continued except in case of signs or symptoms of chorio-amnionitis. Breastfeeding is not recommended in women living with HIV in France, as in industrialized countries. Prophylaxis in the newborn is usually zidovudine for 1 month. In case of significant exposure to HIV perinatally, in particular when, maternal viral load is>1000 copies/mL, prophylactic combination therapy is recommended. Monitoring of the child is necessary to determine whether or not it is free of HIV infection and to monitor possible adverse effects of perinatal exposure to antiretroviral drugs.

DNA fragmentation is higher in spermatozoa with chromosomally unbalanced content in men with a structural chromosomal rearrangement.

It has been previously shown that men with chromosomal structural abnormality had a higher rate of sperm DNA fragmentation. We studied 11 male carriers of a chromosomal structural abnormality (seven with a balanced reciprocal translocation, three with a Robertsonian translocation, one with a pericentric inversion) to determine whether spermatozoa with unbalanced chromosomes were more likely to have fragmented DNA. A sequential method combining analysis of DNA fragmentation using the TUNEL assay followed by analysis of meiotic segregation by fluorescent in situ hybridization was performed on the same spermatozoa. A statistically significant higher number of spermatozoa with unbalanced chromosomal content were found to have fragmented DNA for each man. The rate of spermatozoa with DNA fragmentation was higher than the rate of those without fragmented DNA in particular modes of segregation. Our findings provide a better understanding of the mechanisms involved in male infertility ascribable to chromosomal structural abnormality.

Sperm cephalic vacuoles: new arguments for their non acrosomal origin in two cases of total globozoospermia.

To add new arguments concerning the origin of the sperm-head vacuoles observed under high magnification with interference contrast microscopy, we carried out in two patients with total globozoospermia confirmed using transmission electron microscopy (TEM), a detailed sperm morphometric analysis with high magnification (×6000) under Nomarski contrast, an acrosomal status analysis (using fluorescent labelling with peanut agglutinin (PNA) lectins and anti-CD46 antibodies) and a nuclear status analysis (using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay TUNEL, sperm chromatin structure assay SCSA and aniline blue staining). Our two patients with globozoospermia had relative sperm vacuole areas of 6.3% and 5%, similar to those observed in a reference population of 12 fertile men (5.9%). TUNEL and SCSA assays gave normal results in both patients, although the percentage of immature nuclei using aniline blue staining was increased (27 and 46% for patient 1 and 2 respectively). Cytofluorescence and TEM analysis evidence differences between the two patients: although no acrosomal neither Golgi residue could be detected in patient 1, patient 2 had positive PNA lectin labelling for 9% of spermatozoa and Golgi residues were seen using electron microscopy. Unlike patient 1, a live birth could be obtained after intracytoplasmic sperm injection (ICSI) for patient 2. This descriptive study of two patients with total globozoospermia confirmed using TEM argue in favour of a deep analysis of total globozoospermia before assisted reproductive technology and provides further information on the non-acrosomal origin of the sperm-head vacuoles observed under high magnification.

[Anonymity and gamete donation]. / Anonymat du don de gamètes.

In France the gamete donation is based on the major principles: anonymity, no payment, solidarity and this mode of procreation can be used only if a medical indication is present in recipient couples. In prerequisite and during the revision of the law of bioethics, a wide debate took place about the anonymity of gamete donation. The objectives of this article is to review the concept of the anonymity and its links with the questions of the origin, the secret of the modalities of the conception and the mourning of the fertility, children, donors and the recipient couples waiting for gamete donation. The international situation is also addressed. The contribution of the CECOS, the centers which practice the sperm and the egg donations is highlighted. The anonymity cannot be discussed without addressing all these links and the complexity of this particular mode of conception. To date, the French society has maintained the anonymity in the new law of bioethics.

[Management of an HTLV-1 infected man in assisted reproductive technology]. / Prise en charge en assistance médicale à la procréation d'un patient infecté par HTLV-1.

Management of people infected by HTLV-1 in assisted reproductive technology (ART) is a rare event. Since HTLV is sexually transmitted, HTLV serodiscordant couples have to systematically use condoms. The sperm processing (centrifugation on density gradient) performed for semen of HIV-infected men was applied. Detection of HTLV-1 provirus DNA was negative before and after sperm processing, allowing ART.

In vitro assessment of the adverse effects of antiretroviral drugs on the human male gamete.

This study was designed to investigate the in vitro effects of didanosine, zidovudine, saquinavir and indinavir, commonly used in highly active antiretroviral therapy, on human sperm fertility parameters. Thirty semen samples from healthy men were collected and prepared by gradient density method. Aliquots of 90% fractions with >80% motile spermatozoa were incubated for 1, 3, and 6h with different concentrations of the antiretroviral drugs (20, 40, and 80 µg/ml). Sperm motility was evaluated by computer assisted sperm analysis system. Sperm mitochondrial potential was evaluated using 3,3'-dihexyloxacarbocyanine iodide (DIOC(6)) and the acrosome reaction was examined using pisum sativum agglutinin method. A dose-dependent decrease in sperm motility was observed with saquinavir. Saquinavir also induced a significant time and dose-dependent decrease in mitochondrial potential and an increase in spontaneous acrosome reaction. These findings indicate that, in vitro, higher doses of saquinavir have adverse effects on sperm motility, mitochondrial potential and acrosome reaction.

[Assisted reproductive technologies for serodiscordant couples: desire for child and pregnancy versus the fact of illness]. / Couples sérodifférents dont l'homme est infecté par le VIH et Assistance médicale à la procréation: le désir d'enfant et la grossesse aux prises avec la réalité de la maladie.

Assisted Reproductive Technologies for serodiscordant couples with HIV-infected male partner has been possible since 2000 in French centres such as the CECOS in Toulouse. From the outset, couples in the program meet psychologists or psychiatrists. In the first instance, the results from 40 psychologist led interviews with serodiscordant couples held at the CECOS in Toulouse, identified several challenging ideas. Couples who plan to have children were in a stable long-term relationship and both were involved in managing the illness. Medically assisted procreation awakens in the women a strong desire for children and enables the couples to make plans for the future. But it also reminds the men of their reliance on medical assistance because of the demands made by the medical program, and in case of failure it can destabilise the couples' way of coping with HIV. Subsequently, interviews with 12 couples during pregnancy revealed the overbearing presence of the illness, despite the imminent birth of the desired child. In their responses, women express their anxiety concerning the risk of contamination, and the defences that the men had built up to cope with HIV appeared destabilised, now that the idea of their death is rekindled.

[Assisted reproductive care in serodiscordant couples whose man is infected with HIV]. / Prise en charge en assistance médicale à la procréation des couples sérodiscordants dont l'homme est infecté par le VIH.

Serodiscordant couples whose man is infected by human immunodeficiency virus have actually induced sterility by condom use. Since 2001, in France, assisted reproduction in serodiscordant couples has been facilitated thanks to the decree of 10th May 2001. In spite of the immense social and scientific advances in Assisted Reproductive Techniques, in such couples, limitation of care remains in certain cases. This study reviews current practices in France and other countries. Limits due to present reproductive and virological methods or legal conditions are underlined. In agreement with current scientific knowledge we suggest new modalities of reproductive care in serodiscordant couples with HIV infected men.

Geographic variations in probability of pregnancy in four cities of France.

BACKGROUND: Several studies have described geographic variations in human fecundability, but this phenomenon has almost exclusively been studied at an international level rather than within a given country. Our aim was to describe geographic variations in fecundability, the monthly probability of pregnancy, between four cities of France. METHODS: We conducted a cross-sectional study in four French maternity units from Toulouse, Rennes, Lyons and Paris, among partners of pregnant women. Women were asked about the time to pregnancy (TTP) of their current pregnancy. TTP was analysed with a discrete Cox model allowing to estimate fecundability ratios (FR). RESULTS: Time to pregnancy was defined for 894 couples. There was no strong evidence of heterogeneity in fecundability between the four compared cities (p=0.05 without adjustment and p=0.25 after adjustment for behavioural and medical factors). The highest fecundability was observed in Rennes and the lowest in Toulouse (fecundability ratio (FR)=1.28, 95% CI: 1.01-1.63). Differences in fecundability were smaller between the other cities. CONCLUSION: We highlighted a possibly slightly higher fecundability in Rennes compared to Toulouse. Possible explanations for this finding are discussed. We note that the finding is consistent with previous observations indicating a higher sperm concentration among semen donors in Rennes than in Toulouse.

Sperm DNA fragmentation: threshold value in male fertility.

BACKGROUND: The extent of sperm DNA fragmentation, which can be measured by the TUNEL assay, is one of the determinants of male fertility. However, the clinical application of this test to in-vivo situations is difficult owing to the absence of a statistically validated threshold value. METHODS: The aim of this study was to compare the results of TUNEL assay applied to semen samples from men of proven fertility (n = 47) and patients from an infertile population (n = 66), in order to establish a discriminating threshold value. RESULTS: Infertile patients had a higher mean level of DNA fragmentation than men of proven fertility (40.9 +/- 14.3% versus 13.1 +/- 7.3%, respectively; P < 0.001). The area under the receiver operating characteristics curve was 0.93 for 20% sperm DNA fragmentation. The calculated threshold value for TUNEL assay to distinguish between fertile controls and infertile men was 20%. At this threshold, specificity was 89.4 [95% confidence interval (CI) 83.7-95.1] and sensitivity was 96.9% (95% CI 93.8-100). The positive and negative predictive values of the 20% sperm DNA fragmentation threshold were high: 92.8% (95% CI 87.9-97.5) and 95.5% (95% CI 91.6-99.3), respectively. CONCLUSION: This study demonstrates that sperm DNA fragmentation, as measured by TUNEL assay, is a highly valuable indicator of male fertility.