Jacqueline Saias-Magnan

Sperm cryopreservation before cancer treatment: a 15-year monocentric experience

Sperm banking is an important procedure to preserve fertility before cancer therapy. The aim of this study was to comprehensively analyse cryopreservation activity retrospectively for 1080 patients referred to the sperm bank for sperm cryopreservation before cancer treatment. This study included 1007 patients diagnosed with testicular cancer (TC) (41.7%), lymphoma (26%), other haematological cancers (9.4%) or other types of cancer (22.8%); of these, 29 patients did not produce any semen sample and cryopreservation was impossible for 67 patients. Semen characteristics before treatment were within normal ranges, except moderate asthenospermia. Sperm concentration was significantly lower in TC than in non-TC. Straws from 57 patients (6.3%) were used in assisted reproductive technologies, which led to a 46.8% cumulative birth rate. Straws were destroyed for 170 patients (18.7%) and 140 patients performed semen analyses after cancer therapy. After an average delay of 22.5 months after the end of therapy, 43 patients (30.7%) exhibited azoospermia. This study of a large population of cancer patients revealed a high level of successful sperm storage. Utilization of cryopreserved spermatozoa led to good chances of fatherhood. Nevertheless, sperm banks should be aware of the low rates of straw use and straw destruction by cancer patients.

Sperm cryopreservation in adolescents and young adults with cancer: results of the French national sperm banking network (CECOS)

OBJECTIVE To determine the feasibility of fertility preservation in adolescent males with cancer. DESIGN Large multicenter retrospective study of male patients ≤20 years from 23 centers of a national network of sperm banks over a 34-year period. SETTING Sperm banks. PATIENT(S) A total of 4,345 boys and young men aged 11 to 20 years. INTERVENTION(S) Age, cancer diagnosis, feasibility of sperm banking, and sperm parameters. MAIN OUTCOME MEASURE(S) Description of patients, and success of their fertility preservation. RESULT(S) We observed a mean yearly increase in referred patients of 9.5% (95% confidence interval, 9.1%-9.8%) between 1973 and 2007. Over the study period, the percentage of younger cancer patients who banked their sperm increased, especially in the 11-14 year age group, rising from 1% in 1986 to 9% in 2006. We found that 4,314 patients attempted to produce a semen sample, 4,004 succeeded, and sperm was banked for 3,616. The mean total sperm count was 61.75 × 10(6) for the 11-14 year age group, and 138.81 × 10(6) for the 18-20 year age group. It was noteworthy that intercenter variations in practices involving young patients seeking to preserve their fertility before cancer therapy were observed within this national network. CONCLUSION(S) Our results emphasize the need for decisive changes in public health policy to facilitate the access to reproductive health-care for young cancer patients.

Homozygous deletion of SUN5 in three men with decapitated spermatozoa

A recent study of 17 men with decapitated spermatozoa found that 8 carried two rare SUN5 alleles, and concluded that loss of SUN5 function causes the acephalic spermatozoa syndrome. Consistent with this, the SUN5 protein localises to the head-tail junction in normal spermatozoa, and SUN proteins are known to form links between the cytoskeleton and the nucleus. However, six of the ten SUN5 variants reported were missense with an unknown effect on function, and only one man carried two high confidence loss-of-function (LOF) alleles: p.Ser284* homozygozity. One potential exonic splice mutation, homozygous variant p.Gly114Arg, was not tested experimentally. Thus, definitive proof that loss of SUN5 function causes the acephalic spermatozoa syndrome is still lacking. Based on these findings, we determined the sequence of the SUN5 gene in three related men of North African origin with decapitated spermatozoa. We found all three men to be homozygous for a deletion-insertion variant (GRCh38 - chr20:32995761_32990672delinsTGGT) that removes 5090 base pairs including exon 8 of SUN5, predicting the frameshift, p.(Leu143Serfs*30), and the inactivation of SUN5. We therefore present the second case where the acephalic spermatozoa syndrome is associated with two LOF alleles of SUN5. We also show that the p.Gly114Arg variant has a strong inhibitory effect on splicing in HeLa cells, evidence that homozygozity for p.Gly114Arg causes acephalic spermatozoa syndrome through loss of SUN5 function. Our results, together with those of the previous study, show that SUN5 is required for the formation of the sperm head-tail junction and male fertility.

The impact of drugs on male fertility: a review

Beside cytotoxic drugs, other drugs can impact mens fertility through various mechanisms. Via the modification of the hypothalamic–pituitary–gonadal axis hormones or by non‐hormonal mechanisms, drugs may directly and indirectly induce sexual dysfunction and spermatogenesis impairment and alteration of epididymal maturation. This systematic literature review summarizes existing data about the negative impact and associations of pharmacological treatments on male fertility (excluding cytotoxic drugs), with a view to making these data more readily available for medical staff. In most cases, these effects on spermatogenesis/sperm maturation/sexual function are reversible after the discontinuation of the drug. When a reprotoxic treatment cannot be stopped and/or when the impact on semen parameters/sperm DNA is potentially irreversible (Sulfasalazine Azathioprine, Mycophenolate mofetil and Methotrexate), the cryopreservation of spermatozoa before treatment must be proposed. Deleterious impacts on fertility of drugs with very good or good level of evidence (Testosterone, Sulfasalazine, Anabolic steroids, Cyproterone acetate, Opioids, Tramadol, GhRH analogues and Sartan) are developed.

Faisabilité de la congélation embryonnaire dans la préservation de la fertilité féminine

With the improvement of the anticancerous treatments, the preservation of the feminine fertility before gonadotoxic treatment tends at present to stand out as a legal obligation, with a duty of information to patients. When emergency IVF can be performed, the cryopreservation of embryos is the best mastered method which offers most chances to patients to obtain a pregnancy after cancer remission thanks to the transfer of frozen embryos. This article proposes an overview about the indications, the feasibility and the ethical and practical limitations of IVF emergency for embryo freezing before gonadotoxic anticancerous treatment.

Should sperm be cryopreserved after spinal cord injury

In spinal cord injured (SCI) patients, three main factors may cause infertility: erectile dysfunction, ejaculatory dysfunction and impaired semen quality. This letter aims to discuss how we can manage SCI patients’ fertility in accordance with patient-centred care. For such SCI patients aged 20 to 40, having children represents hope for the future. Furthermore, it is a way to rebuild a life after the spinal injury and must be seen as an important part of the rehabilitation program. We suggest that sperm cryopreservation may contribute to patient-centred care management of SCI patients’ fertility, although there is no scientific evidence that cryopreservation will improve fertility outcome after SCI. Indeed, sperm cryopreservation is an affordable and simple technique in specialised centres with trained staff. Here, a protocol to manage SCI patients’ fertility is discussed: we propose PVS for sperm banking to all SCI patients after the phase of spinal shock during the rehabilitation program. If live sperm are retrieved, they are frozen and stored; however, if no live sperm are retrieved, electroejaculation and/or surgical sperm extraction are proposed only for patients who desire biological fatherhood. Prospective studies on the evolution of semen parameters, ejaculatory dysfunction, post-infectious obstructions and spermatogenesis impairment in chronic SCI patients are urgently needed to provide robust data for the evidence-based management of SCI patients’ fertility. Even if use rates are expected to be low, sperm banking may be a simple and affordable preventative measure for selected male SCI patients.RésuméChez les patients blessés médullaires (BM), trois facteurs principaux peuvent provoquer une infertilité : la dysfonction érectile, la dyséjaculation et l’altération des paramètres spermatiques. Cette lettre a pour but de discuter comment gérer la fertilité des BM en accord avec le principe de soins axés sur le patient. Pour ces patients principalement âgés de 20 à 40 ans, la paternité représente un espoir pour le futur et un moyen de se reconstruire après la lésion médullaire ; cet aspect doit être considéré comme une partie importante du programme de réhabilitation. Nous suggérons que la cryoconservation de sperme (CS) chez le BM pourrait contribuer au principe de soins axés sur le patient, bien qu’il n’y ait pas de preuve scientifique que la CS améliore les résultats en assistance médicale à la procréation. En effet, la CS est une technique abordable et simple dans les centres spécialisés au personnel entraîné. Un protocole de prise en charge de la fertilité du BM est discuté : nous proposons la stimulation vibratoire pénienne à tous les patients BM après la phase de choc spinal, au cours du séjour en rééducation fonctionnelle. Si des spermatozoïdes sont obtenus dans l’éjaculat, ils sont cryoconservés ; dans le cas contraire, nous proposons une électroéjaculation et/ou un prélèvement chirurgical de spermatozoïdes seulement aux patients présentant un désir parental actuel. Afin d’assurer une gestion de la fertilité des BM basée sur des preuves scientifiques solides, des études prospectives de l’évolution à long terme des paramètres spermatiques, de la capacité à éjaculer, des obstructions post-infectieuses du tractus séminal et des altérations de la spermatogenèse chez les patients BM chroniques sont urgemment nécessaires. Dans l’attente de ces données, même si les taux d’utilisation attendus des paillettes sont faibles, la CS pourrait être une mesure préventive simple et abordable pour les patients BM.

Case report of apoptosis in testis of four AZFc-deleted patients: increased DNA fragmentation during meiosis, but decreased apoptotic markers in post-meiotic germ cells

AZFc deletions of the Y chromosome are the major known genetic cause of spermatogenetic failure. Meiotic studies have shown a prevalence of synaptonemal complex fragmentation and an excess of early-stage sperm cells, suggesting that the maturation block could involve apoptosis. We present a prospective and observational study of apoptotic markers in the sperm of four AZFc-deleted patients and two non-obstructive azoospermic controls without an AZFc deletion. Polycaspases assays and terminal deoxynucleotidyl transferase dUDP nick-end labelling (TUNEL) assays were combined to evaluate the incidence of apoptosis in pre-meiotic, meiotic and post-meiotic germs cells identified, respectively, using anti-melanoma-associated antigen A4 (MAGE-A4), anti-synaptonemal complex protein 3 (SCP3) and anti-sperm acrosome membrane-associated protein 1 (SPACA1) antibodies. We detected apoptosis at all stages of AZFc-deletion spermatogenesis. Using the caspase assay, the incidence of positive cells was found to be heterogeneous for pre-meiotic (from 4.8 to 84.5%) and meiotic stages (from 7.9 to 57.6%), while for post-meiotic cells, the mean incidence was 6% in AZFc-deleted patients compared with 26.5% in controls (P < 0.05). Using the TUNEL assay, the mean percentage with DNA fragmentation for meiotic cells was 54.0% in AZFc-deleted patients compared with 20.3% in controls (P < 0.05), while the percentage of TUNEL-positive post-meiotic cells ranged from 5.3 to 44.7%. Spermatocyte loss in AZFc-deleted patients occurs via the apoptotic pathway. In post-meiotic cells, the lower incidence of apoptosis in testis from three of the four AZFc-deleted patients, compared with controls, is consistent with AZFc deletions having little negative impact on sperm quality.

Sperm donor conception and disclosure to children: a 10-year retrospective follow-up study of parental attitudes in one French center for the study and preservation of eggs and sperm (CECOS)

OBJECTIVE To evaluate the percentage of parents in one French center for the study and preservation of eggs and sperm who disclose their use of donated spermatozoa to their children. DESIGN A questionnaire survey of couples who had a child using donated spermatozoa. SETTING University hospital laboratory. PATIENT(S) One hundred five couples. INTERVENTION(S) Questionnaire sent by mail. MAIN OUTCOME MEASURE(S) The percentage of parents who disclose their use of donated spermatozoa to their child. RESULT(S) Among the 157 questionnaires sent, 105 couples answered, which corresponded to 138 children. There were 40 (38%) couples who had already disclosed the donor origin to their child and 65 (62%) who had not. Of the 40 couples who disclosed the donor origin, 37 (93%) had intended to do so before making use of assisted reproductive techniques (ART), but two (5%) had not wanted to do so before ART. Among the 65 couples who did not inform their child, 42 (65%) planned to inform their child soon, but 20 (31%) wanted to keep the sperm origin secret. Of the 20 couples who wanted to keep the origin secret, nine couples had told other persons about the gamete donation but had not informed their child and do not intend to inform their child in the future. CONCLUSION(S) This first report about disclosure attitude in a large cohort of parents of donor-conceived offspring in France showed that most parents had already disclosed their use of donated spermatozoa to their children or intended to disclose it soon and had an attitude after birth consistent with their intentions prior to ART.

Le blessé médullaire: quel sperme et quelle prise en charge en Assistance médicale à la procréation ?

Men with spinal cord injury present a unique infertile population. Only 10 % of them can father children without medical assistance, owing to potential impairments in erection, ejaculation and semen quality. The algorithm typically followed is to retrieve semen by Penile Vibratory Stimulation, in case of failure by Electro Ejaculation. Most of these patients have normal sperm concentrations but abnormally low sperm motility and vitality in the ejaculate. The reasons for poor semen quality in spinal cord injured men are reviewed. If semen cannot be obtained by Electro Ejaculation, or if the ejaculate from Penile Vibratory Stimulation or Electro Ejaculation contains an insufficient quantity or quality of sperm for in vitro fertilization with intracytoplasmic sperm injection, then retrieval of sperm from reproductive tissues is attempted. Despite abnormal semen quality, successful pregnancies with sperm from spinal cord injured male partners have occurred by intravaginal insemination, intrauterine insemination, and in vitro fertilization with intracytoplasmic sperm injection. The prevailing pregnancy and fecundity rates in couples with a spinal cord injured male partner are reviewed.