Prise en charge des troubles de la reproduction chez l’adolescent

Adolescence is a period marked by the search for sexual identity. How do paraplegic or quadriplegic teenagers develop their sexual identity? How can the nursing team help them in this process? The authors study erection and the quality of sexual relations and then examine the problem of procreation. Early, practical information adapted to the neurological definition of the spinal cord injury is essential, with preservation of sperm prior to the development of urological and infectious complications. The authors report their experience of 24 paraplegic or tetraplegic teenagers at the CMPA in Neufmoutiers and the CECOS at Cochin Hospital in Paris.     

Préserver la fertilité chez les adolescents traités pour un cancer. Le point de vue du psycho-oncologue

The question of fertility is a major concern for young adults successfully treated for cancer, which is why semen preservation should be proposed to all adolescent boys prior to treatment of a cancer. This proposal is part of the oncologist’s approach to prevent sequelae. To ensure that semen cryopreservation is conducted under good conditions and is accepted by the adolescent, it is important to have a good understanding of the psychopathology and behaviour of adolescents with cancer: their preoccupation with their body, their appearance, their sexuality, their relationships to their peers and to their parents, their value and narcissism, their identity. This helps the clinician to understand and overcome the various reasons for their difficulty (and to lessen the painful feeling of failure) or their reticence to perform semen cryopreservation: paralysed by the diagnosis of cancer, sexual inhibition, lack of understanding and ignorance, pessimism concerning outcome, incapacity to project into the future, poor relationship with parents, discredit of parenthood, fear of transmitting the cancer, etc. A good understanding of these elements can avoid an excessively rapid acceptance of a superficial opposition to this procedure that the patient could subsequently regret. Closer collaboration should be developed between oncology-haematology departments and CECOS units to provide suitable information material to adolescents, to improve the understanding of the specific psychology of adolescents, and to understand the parents’ positions.     

Données descriptives de l’activité d’Assistance médicale à la procréation avec don de spermatozoïdes au sein des CECOS de 1973 à 2006 en France

Introduction

The first CECOS (Centre for study and conservation of human eggs and sperm) was created in 1973 by Georges David and till today, most of the activity of sperm donation in France is managed by the CECOS. This work presents a detailed report of the activity of sperm donation between 1973 and 2006 in this French CECOS network.

Material and methods

Annual activity reports have been compiled by the French CECOS network since 1973. We have collected and analysed these annual reports in order to establish a general estimation of the activity of sperm donation in France during the period of more than 30 years.

Results

Sixty-nine thousand nine hundred forty-five couples asked for assisted reproductive techniques with sperm donation (mainly artificial insemination) to conceive their first child. About 20% of these couples tried to conceive a second or third child. A total of 44,045 children were thus conceived with the effective contribution of 10,347 donors of spermatozoa (out of 16,971 donors who came in the centres for a donation). This report of activity is the largest ever published.     

Prévention des risques d’infertilité liés aux traitements antitumoraux dans le cancer du testicule

In recent years, chemo- and radiotherapy for cancer patients have become increasingly successful, and sustained remissions have been achieved. However in young men, most of the current therapies still presently induce temporary or permanent infertility without any means of prediction. This is also true in the case of testicular cancer which is now the most frequent cancer in young adults males. Moreover, this problem is particularly crucial in patients with a testicular cancer since they have a poor semen quality before any antitumoural therapy. The present paper largely based on data accumulated over 25 years at CECOS Paris Cochin reviews the modalities and clinical usefulness of semen cryopreservation in young men with testicular cancer. Recent use of cryopreserved semen samples through ART has provided a growing number of pregnancies. These new data strongly demonstrate that semen cryopreservation should be offered to all men diagnosed with a testicular cancer since it provides the only reasonable chance of establishing a pregnancy after therapy.     

Utilisation des spermatozoïdes cryoconservés: fréquence et résultats

Semen cryopreservation has become a major activity of CECOS units. In 2002, 2,323 patients were referred to a CECOS unit for semen cryopreservation prior to radiotherapy or chemotherapy. Cryopreservation of one or several semen specimens was performed for 2,124 patients, which represents a total of more than 60,000 straws per year. The two diseases mainly concerned by cryopreservation prior to treatment with a high risk of sterilization are testicular cancer (about 40% of requests) and lymphomas (about 30% of requests). Specimens are generally stored for several years. The most frequent indications are testicular cancer (40% of the patients) and lymphomas (30% of the patients). Due to the continuing improvement of treatment, the subsequent fertility prognosis of patients has improved over recent years, but often remains difficult or even impossible to predict. An assessment of the effective use of these frozen gametes and the results obtained therefore appeared to be interesting. During 2002, 304 men requested the use of their cryopreserved semen. More than 1,000 straws were thawed and used for insemination (195 insemination cycles, 12 pregnancies obtained) orin vitro fertilization (25 conventional IVF cycles, 8 pregnancies; 257 IVF-ICSI cycles, 57 pregnancies). A retrospective cumulative study conducted in 2001 with the collaboration of 15 of the 23 CECOS units calculated, for each year, among patients in whom cryopreservation could be performed, the percentage of patients who subsequently requested the use of straws between the date of cryopreservation and 2001. This percentage varied between 5% and 10%, depending on the time since freezing. Calculation of the percentage of patients for whom destruction of straws was performed, either at the patient’s request, or because of the patient’s death, was also performed according to the same methodology. The percentage of destruction because of the patient’s death varied between 5% and 9%. The percentage of destruction of straws at the patient’s request was close to or greater than 15%, when the storage time exceeded 3 years. The percentage of patients lost to follow-up remains low in these indications for cryopreservation, ranging between 3% and 6% depending on the year. These data are globally coherent with the data reported in the literature. Although the use of straws is not the most frequent outcome of semen cryopreservation, freezing of gametes must nevertheless always be proposed to patients, as their subsequent fertility often remains difficult to predict. Progress in methods of medically assisted procreation also allow a good chance of pregnancy even when few viable spermatozoa have been preserved.     

Le don de sperme

Since its creation, the recruitment of donors has been a constant difficulty of the CECOS. Donors have to be sollicited directly or indirectly. The limited number of pregnancies from the same donor obliges the CECOS to recruit constantly new ones. They cannot call for the same donors periodically. Sperm donation, like other human products, should be done with the free consent of the donors. Its aim is to allow the conception of children outside the family organization of the donor. This motivates some men to accept donation and at the same time démotivates many of them. Hence the necessity of advertisment for sperm donation to favor recruitment among a large population.     

Fertilité après cancer du testicule

Objectives

To study the fertility of patients treated for testicular cancer and to identify predictive factors of infertility after treatment.

Material and Methods

314 men with germ cell tumor, followed by the CECOS Midi-Pyrénées center between 1978 and 1998, were included in the study. They were evaluated retrospectively and interviewed by a mailed questionnaire concerning their reproductive history. If they failed to respond to the questionnaire, they were contacted twice by mail, and once by telephone. The response rate was 92%.

Results

The reproductive history of 277 men was known: 138 men had tried to have a child. 91 (66%) succeeded and 47 (34%) failed to achieve a “spontaneous” pregnancy. Age greater than 25 (p<0.004), a history of undescended testis, and a sperm count lower than 10 million per ml were inversely correlated with fertility (p<0.004, p<0.01, p<0.0001, respectively). However, no relationship was found between radiotherapy or chemotherapy and fertility after treatment.

Conclusion

Men treated for testicular cancer are at high risk of infertility. We identified various prognostic factors for fertility after treatment for testicular cancer: radiotherapy and chemotherapy had no significant effect on fertility.     

Cryoconservation de spermatozo?des avant vasectomie: utilité et paradoxes à travers l’activité des CECOS

Sperm banking when consulting for vasectomy can appear as a paradox. Around 12% of the men who decide to have a vasectomy consult in a CECOS for sperm cryopreservation before surgery. Among these men, less than 5% will use their frozen sperm. In about 10 years, artificial insemination has been quite abandoned and in vitro fertilization is now widely used by these patients when they desire a child in a new couple. It is thus time to ask wether cryopreservation of sperm is still to be proposed before vasectomy.     

Cancer chemotherapy induces cardiotoxicity by targeting cardiac stem cells

Overwhelming data indicate that cancer survivors are at higher risk of cardiovascular diseases because chemotherapy induces cardiotoxicity. Mechanistic explanation of this phenomenon is necessary to advise the clinical practice on the prevention of cardiotoxicity in cancer patients. Here we propose that chemotherapy induces cardiotoxicity by inadvertently interrupting the homeostasis of cardiac stem cells and depleting the resident cardiac stem cells pool. As a result, the heart loses the capability of regeneration and repair and demonstrates the cardiotoxicity symptoms. Our hypothesis is supported by several lines of emerging evidence: the high incidence of cardiotoxicity in paediatric cancer patients who still have more cardiac stem cells in the myocardium; the rescue of anthracycline cardiomyopathy by injection of cardiac stem cells; and the adverse cardiotoxicity induced by inhibitors of oncogenic kinases or pathways which target cardiac stem cells besides cancer cells. This may promote our growing appreciation that cardiac stem cells represent new targets of chemotherapy that contribute to cardiotoxicity and open up novel strategies for the preservation or expansion of the cardiac stem cells pool to overcome cardiotoxicity associated with chemotherapy.     

Benign and Malignant Renal Cells Are Differentially Inhibited during Prolonged Organ Preservation

The worry of potential residual renal cancer cells in donor kidney after resection of small renal cancer impedes the extensive use of such controversial donor source. To explore the impacts of organ preservation process on the survival of renal cancer cells, we detected cell proliferation and viability of benign and malignant renal cell lines and clinical renal samples after treated with simulated organ preservation process. It was found that the viability and proliferation of malignant renal cells are inhibited much more than that of benign renal cells during prolonged organ preservation. The inhibition of proliferation in benign renal cells is fully reversible, while in malignant renal cancer cells is not fully reversible after a certain time. So potential residual renal cancer cells could be partly inhibited and eliminated by organ preservation process.     

Global uptake of fertility preservation by women undergoing cancer treatment: An unmet need in low to high-income countries

Although the incidence of cancers is on the rise globally, mortality has continued to decrease due to advances in early detection and treatment. Cancer treatments such as chemotherapy and radiotherapy can impact the reproductive capacity of survivors by inducing premature ovarian failure and subsequent infertility causing significant psychological distress with decreased quality of life. Despite the increasing need for fertility preservation services for the rising number of cancer survivors and the recent advances in assisted reproductive technology, many women with cancers in low, middle, and to a lesser extent, high-income countries have no access to these services. This article, therefore, presents an overview of the effect of cancer treatment on fertility, options of fertility preservation, and factors influencing fertility preservation utilization by women who had a cancer diagnosis. In addition, we discuss the availability, practices, and outcomes of fertility preservation services in low, middle, and high-income countries and highlight pragmatic steps to improving access to oncofertility care for women with cancers globally.     

Laparoscopic ovarian transposition before pelvic radiation in rectal cancer patient: safety and feasibility

Background

Infertility due to pelvic radiation for advanced rectal cancer treatment is a major concern particularly in young patients. Pre-radiation laparoscopic ovarian transposition may offer preservation of ovarian function during the treatment however its use is limited.

Aim

The study investigates the safety, feasibility and effectiveness of pre-radiation laparoscopic ovarian transposition and its effect on ovarian function in the treatment o locally advanced rectal cancer.

Methods

Charts review of all young female patients diagnosed with locally advanced rectal cancer, underwent laparoscopic ovarian transposition, then received preoperative radiotherapy at king Faisal Specialist Hospital and Research Centre between 2003?C2007.

Results

During the period studied three single patients age between 21?C27?years underwent pre-radiation laparoscopic ovarian transposition for advanced rectal cancer. All required pretreatment laparoscopic diversion stoma due to rectal stricture secondary to tumor that was performed at the same time. One patient died of metastatic disease during treatment. The ovarian hormonal levels (FSH and LH) were normal in two patients. One has had normal menstrual period and other had amenorrhoea after 4?months follow-up however her ovarian hormonal level were within normal limits.

Conclusions

Laparoscopic ovarian transposition before pelvic radiation in advanced rectal cancer treatment is an effective and feasible way of preservation of ovarian function in young patients at risk of radiotherapy induced ovarian failure. However, this procedure is still under used and it is advisable to discuss and propose it to suitable patients.     

Que représente l’autoconservation de sperme pour l’homme atteint d’un cancer?

Over the last fifteen years, oncologists, after having informed their patients about the toxic effects of chemotherapy and radiotherapy on spermatogenesis, have fairly systematically referred these men to CECOS units for semen cryopreservation. Semen cryopreservation is performed in the context of a serious disease and must achieve its objective, i.e. facilitate this procedure for the patient and ensure satisfactory results in the case of subsequent use. Men must be free to refuse this option for personal reasons. Particular care is required for young men and adolescents, who may be very reticent about masturbation, even when prescribed by the doctor.     

Don anonyme, secret du don et symbolique

Based on the psychological interviews we had at CECOS with sperm donors and with requesting couples, and following the analysis of testimonials of children born through donations, we seek to outline that it is not mainly the anonymous donors who raise an issue, but the secret on the nature of the donation itself. It all becomes a family secret as the donation is not well received by the parents. This causes negative effects when the announcement is made lately and it is forbidden to talk about it.     

Optimizing methods for human testicular tissue cryopreservation and spermatogonial stem cell isolation

Cryopreservation of testicular tissue before cancer therapy for fertility preservation in prepubertal boys with cancer is of great interest in reproductive medicine. Isolation of spermatogonial stem cells (SSCs) from cryopreserved tissues would be a suitable cell source to re-establish spermatogenesis after cancer therapy. We herein establish optimized protocols for cryopreservation of human testicular tissue and isolation of SSCs from cryopreserved tissue. We developed a freezing protocol that provided high testicular cell viability and supported structural integrity and tubular epithelium coherence similar to fresh tissue. Then, we established a protocol that allowed efficient isolation of functional SSCs from cryopreserved tissues. Isolated cells were found on the testicular basement membrane after xenotransplantation. Our results demonstrated the preservation of testicular tissue structure and high cell viability with efficient isolation of SSCs after testicular cryopreservation, which is promising for future therapeutic applications in fertility preservation.     

Inhibition of homologous recombination by the PCNA-interacting protein PARI

Inappropriate homologous recombination (HR) causes genomic instability and cancer. In yeast, the UvrD family helicase Srs2 is recruited to sites of DNA replication by SUMO-modified PCNA, where it acts to restrict HR by disassembling toxic RAD51 nucleofilaments. How human cells control recombination at replication forks is unknown. Here, we report that the protein PARI, containing a UvrD-like helicase domain, is a PCNA-interacting partner required for preservation of genome stability in human and DT40 chicken cells. Using cell-based and biochemical assays, we show that PARI restricts unscheduled recombination by interfering with the formation of RAD51-DNA HR structures. Finally, we show that PARI knockdown suppresses the genomic instability of Fanconi Anemia/BRCA pathway-deficient cells. Thus, we propose that PARI is a long sought-after factor that suppresses inappropriate recombination events at mammalian replication forks.     

Effects of malignancies on fertility preservation outcomes and relevant cryobiological advances

A decrease in cancer deaths has resulted in the possibility of child bearing for many young adult cancer survivors. Most antitumor treatment modalities are detrimental to female fertility, and methods for fertility preservation before gonadotoxic treatment, including cryopreservation of oocytes, embryos and ovarian tissue, have therefore been developed. This review focuses on the ovarian function of cancer patients, the safety and efficacy of fertility preservation methods, and the pregnancy outcomes of these patients. Breast cancer and hematological tumors constitute the majority of cancers in reproductive-aged female oncology patients. Ovarian function may not be impacted by breast cancer cells, while in patients with hematological malignancies, decreases in anti-Müllerian hormone and antral follicle counts have been demonstrated. In most cases, patients can undergo ovarian stimulation without delaying treatment, and a new stimulation protocol known as dual stimulation, which may be more efficient, has now been developed. Birth outcomes are also acceptable in cancer patients.     

Preservation of fertility in females treated for cancer

Advancements of diagnosis and treatment have substantially improved cancer survival rates in the last few decades. The increasing number of survivors focuses attention on long-term effects caused by cancer treatment and its impact on quality of life. Ovarian failure is one of the major sequelae of cytotoxic chemotherapy and/or radiotherapy in female children and reproductive-age women. Oncologists should address the patients about fertility preservation options before therapy. Embryo cryopreservation is the only well-established method for females in preserving fertility; however other strategies including ovarian suppression, ovarian transposition and cryopreservation of oocytes and ovarian tissue are still experimental. Patients need advice and to know which are the most practical options for them. This article reviews the available fertility preservation methods in women, and the related issues including normal physiology of the ovary, effect of anticancer therapy on fertility, role of the oncologist and ethics. We performed a MEDLINE search from 1971 to 2011 in a similar way as Jensen et al. 2011, using the following MeSH terms: antineoplastic agents; ovarian failure; premature; infertility, female; fertility preservation; child and cancer; reproductive technologies, assisted.     

Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response

Apoptosis serves as a protective mechanism by eliminating damaged cells through programmed cell death. After apoptotic cells pass critical checkpoints, including mitochondrial fragmentation, executioner caspase activation, and DNA damage, it is assumed that cell death inevitably follows. However, this assumption has not been tested directly. Here we report an unexpected reversal of late-stage apoptosis in primary liver and heart cells, macrophages, NIH 3T3 fibroblasts, cervical cancer HeLa cells, and brain cells. After exposure to an inducer of apoptosis, cells exhibited multiple morphological and biochemical hallmarks of late-stage apoptosis, including mitochondrial fragmentation, caspase-3 activation, and DNA damage. Surprisingly, the vast majority of dying cells arrested the apoptotic process and recovered when the inducer was washed away. Of importance, some cells acquired permanent genetic changes and underwent oncogenic transformation at a higher frequency than controls. Global gene expression analysis identified a molecular signature of the reversal process. We propose that reversal of apoptosis is an unanticipated mechanism to rescue cells from crisis and propose to name this mechanism "anastasis" (Greek for "rising to life"). Whereas carcinogenesis represents a harmful side effect, potential benefits of anastasis could include preservation of cells that are difficult to replace and stress-induced genetic diversity.     

Fertility preservation and preimplantation genetic assessment for women with breast cancer

Breast cancer is the most common cancer diagnosed among reproductive aged women, and its treatment can compromise future fertility. Options for fertility preservation include oocyte or embryo cryopreservation after ovarian stimulation (OS), which are the most established choices and are applicable for adult women with cancer. Ovarian tissue freezing may also be appropriate, as it offers potentially the least delay. The recognisation of the role of BRCA1 and BRCA2 mutations in some women has led to the involvement of preimplantation genetic diagnosis (PGD), recently renamed preimplantation genetic testing for monogenic disorder (PGT-M), whereby embryos are created by IVF and cell(s) are removed and genetically analyzed for specific disease-related mutations. PGT-M offers a valid option for women wishing to avoid transmission of the predisposition for hereditary breast cancer to their offspring. The aim of this paper is to provide an overview of the factors that influence fertility preservation in newly diagnosed breast cancer patients, and to illustrate the option of PGT-M to enable conception of an unaffected child.