Fertility preservation after fertility-sparing surgery in women with borderline ovarian tumours.

OBJECTIVE: To present a case series of women with borderline ovarian tumours (BOTs) who underwent oocyte vitrification in addition to fertility-sparing surgery. STUDY DESIGN: Observational study of all women referred to a French fertility preservation unit between 2015 and 2019 for counselling regarding a fertility preservation (FP) strategy after BOT fertility-sparing surgery. All eligible women underwent one or more cycles of controlled ovarian stimulation (COS) using an antagonist protocol, followed by oocyte retrieval. Metaphase II (MII) oocytes were vitrified. RESULTS: Twenty-five women with BOTs were referred during the study period. Among them, 11 women underwent at least one cycle of COS. One hundred and seven MII oocytes were vitrified. The mean number of vitrified MII oocytes per woman was 9.7 (standard deviation 5.2). Five live births were reported during follow-up of four women with vitrified oocytes: three spontaneous pregnancies, one in-vitro fertilization cycle with fresh embryo transfer, and one live birth after return of vitrified oocytes. CONCLUSION: Conservative surgery for BOTs offers a high spontaneous pregnancy rate but has a higher risk of relapse than radical treatment. Furthermore, women who undergo conservative BOT surgery have a higher risk of surgery-induced premature ovarian failure. Oocyte cryopreservation after COS appears to be an effective technique after the conservative management of BOTs in women of reproductive age. Although the available short-term data are reassuring, further long-term studies evaluating the safety and cost-effectiveness of this systematic FP strategy after BOT fertility-sparing surgery are required.

The impact of drugs on male fertility: a review.

Beside cytotoxic drugs, other drugs can impact men's 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.

[Fertility preservation among patients with cancer: report of a French regional practical experience]. / Préservation de la fertilité en oncologie : bilan des pratiques en Région PACA-Corse.

OBJECTIVE: Improvement in cancer treatments has led to reconsider the importance of quality of life after cancer, especially concerning maintening the potential of fertility since it is often altered after healing. Our objective was to estimate the knowledge and practices of the physicians in the field of Oncology in a French Region (Provence Alpes- Côte d'Azur). PATIENTS AND METHOD: Prospective survey, conducted between January and April 2012, amongst oncologists working in Provence Alpes Côte d'Azur region, through questionnaires distributed during multidisciplinary meetings in oncology. RESULTS: Among 225 replies, 54% of the physicians had sent no patient to any oncofertility consultation during the previous six months (n=120). Besides, 33% of the oncologists (n=68) declared they had difficulties in addressing their patients to oncofertility consultation, and 58% of them (n=39) considered they lacked information on techniques and indications of fertility preservation. CONCLUSION: This study provides an estimation of the current practices in PACA region concerning oncofertility and underlines the physicians' need of information. In this context, the regional oncology network has set up a regional network « cancer and fertility ¼ in order to facilitate the access to fertility preservation prior to any potentially sterilizing treatment for all patients.

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.

[Female fertility preservation: feasibility of emergency IVF for embryo freezing]. / 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.

[Do couples who procreate through sperm donation inform their children?]. / Les couples qui procréent par don de sperme en informent-ils leurs enfants ?

OBJECTIVES: An amendment to the French bioethics law allowing children conceived by gamete donation to know the identity of donors is proposed, while no study can assess the proportion of parents in France that disclose the nature of conception to their donor conceived offspring. The aim of our study was to know whether couples who wish to inform their offspring actually did it. PATIENTS AND METHODS: We sent a questionnaire to parents who had expressed an intention to disclose the nature of conception to their future offspring conceived by sperm donation. This allowed us to evaluate the number of couples who inform their offspring, and the couple and offspring feelings when information was given. RESULTS: Among 38 questionnaires sent, 20 couples answered. Fourteen informed their offspring about the nature of conception, most having lived serenely this moment. 47% of offspring have reacted with indifference. While 19 couples informed their friends or family, six couples did not inform their offspring, and two of them no longer want to disclose anymore. CONCLUSION: Careful thought before the beginning of assisted reproductive technology and support after birth are needed to help couples communicate information to their offspring. Without this communication, any policy of openness to know donor related data seems vain.

[Initial results of a novel technique for sperm retrieval in male infertility due to refractory retrograde ejaculation]. / Résultats préliminaires d'une nouvelle technique de recueil du sperme vésical en présence d'éjaculation rétrograde réfractaire au traitement médical.

AIMS: To describe and evaluate a novel technique of spermatozoa retrieval from patients suffering from infertility secondary to refractory retrograde ejaculation. METHOD: Prospective study to compare mobility and vitality of spermatozoa obtained from urine (U) after oral modification of chemical parameter (PH, Osmolarity) versus from endovesical instillation of sterile spermatozoa culture medium before ejaculation (F). Patients were their own controls. Twelve month prospective follow-up was achieved to document the results of assisted procreation. RESULTS: Eight patients were included and mobility and vitality were improved in all patients after F technique was compared to U technique. With U technique, eight patients on eight had negative defrost test; after F technique, seven patients on eight had a positive defrost test and could therefore have access to assisted reproduction techniques. Four couples had five ICSI and obtained three pregnancies leading to five births. CONCLUSION: Endovesical instillation of sterile spermatozoa culture medium before ejaculation was a safe and effective technique to improve spermatozoa quality in male infertility related to refractory retrograde ejaculation.

[The spinal cord injured patient: semen quality and management by Assisted Reproductive Technology]. / 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.

[What are at present the real hopes of pregnancy after ovarian cryopreservation?]. / Quels sont actuellement les espoirs réels de grossesse après cryoconservation ovarienne?

Survival rates for cancers that occur in childhood and adolescence have improved over the last decades, and preservation of future fertility in these patients has become a relevant issue. Premature ovarian failure is a consequence of exposing women to chemotherapeutic drugs and ionizing radiation. Ovarian cryopreservation is an alternative to cryopreservation of embryos or oocytes for theses patients. Ovarian cryopreservation aims to reimplant ovarian tissue after complete remission into the pelvic cavity (orthotopique site) or a heterotopic site like the abdominal wall or the forearm. In vitro folliculogenesis, that aims at the maturation of ovarian cortex primordial follicles cryopreserved for a FIV, is still in an experimental research stage. In this review, the objective was to evaluate the real hopes of pregnancy after ovarian cryopreservation. Indeed, many teams offer ovarian cryopreservation at present time, although only two pregnancies have been achieved to date. In both cases, it can be discussed whether the fertilized oocyte originated from the transplant or from the native ovary. Furthermore, the potential for reintroduction of cancerous cells may limit this technique in cancers that are known to have a risk of ovarian dissemination. The hopes engendered by ovarian cryopreservation, but also its limits, must be explained to the patients before an ovarian surgery for cryopreservation.

[Ovarian cryopreservation: clinical and ethical problems arisen further to study on cases of ovarian cryopreservation]. / Cryoconservation ovarienne: problèmes cliniques et éthiques. A propos d'une série de cas d'autoconservation de tissu ovarien.

OBJECTIVE: An early ovarian failure and sterility, on patients often still young, may result from some of the anticancerous treatments. Ovarian cryopreservation is a research way for fertility restoration on patients who will have gonadotoxic treatment. The aim of our work was to study the cases of ovarian tissue preserved in our Department, enabling us to assess the clinical and ethical problems of this technique. PATIENTS AND METHODS: A retrospective study was conducted from January 2001 onwards up to October 2005, on 14 patients, whose ovarian cortex was frozen our the University Fertility Center (Hôpital de la Conception, Marseille, France). RESULTS: In our study, the patients' average age was 17+/-5.5 and the median was 14 years [13-24]. Eight patients were under 18 (11+/-3-years-old). The cryopreservation indications were especially haematological (N = 9). More than half of the patients (N = 8) had undergone a gonadotoxic treatment before ovarian cryopreservation. DISCUSSION AND CONCLUSION: Ovarian cryopreservation is still a recent technology in reproductive medicine. The future of ovarian tissue after thawing, with its different techniques of autograft, is still not consensual. Experimental research remains essential to improve the freezing protocols and ovarian transplant in human medicine.

[Optimization of artificial inseminations with donor semen: a four-year experience]. / Optimisation des résultats d'inséminations intra-utérines uniques avec sperme de donneur: bilan de quatre ans d'activité.

OBJECTIVE: Our aim was to analyse the results of a donor insemination program using ovarian stimulation, swim-up sperm preparation and intrauterine insemination proposed to women with a maximum age of 39. Incidence of several clinical and biological parameters on success rates was investigated. PATIENTS AND METHODS: Retrospective analysis of the results of 249 cycles performed in 106 couples during a four-year period is reported. RESULTS: Overall pregnancy rate of 28.1% and delivery rate of 22% per cycle were achieved, with a multiple pregnancy rate of 11.4%. Most of the pregnancies (84%) were obtained before the fourth insemination. Among the different parameters studied the total number of motile sperm inseminated was found to be the most important factor for success rate: pregnancy rate per cycle reached 40.4% if more than 1.5 million progressive sperm were inseminated vs. 24.7% if they were less than 1.5 million (P<0.05). DISCUSSION AND CONCLUSION: In precise conditions, outcome of inseminations with donor semen can reach satisfying pregnancy rates, being a valuable help for couples suffering of long-time infertility.

Meiotic anomalies in infertile men with severe spermatogenic defects.

BACKGROUND: This study was aimed at evaluating the rate of pairing failure in pachytene spermatocytes of patients presenting either an obstructive (O) or a non-obstructive (NO) infertility. METHODS: Forty-one patients and 13 controls underwent testicular biopsy. Among the patients, 19 had an O infertility and 22 a NO infertility. Preparations of all patients and controls were Giemsa-stained, and synaptonemal complexes from nine of these patients and one control were immunostained. RESULTS: In all, 2931 pachytene nuclei were analysed. The mean rate of asynapsed nuclei from the NO group (25.4%) was significantly higher than that of the O group (9.8%). There was no significant difference between the O group and the controls (10.6%). Immunocytochemistry showed that the number of pachytene nuclei decreased from the early to late pachytene sub-stage in all patients. Two NO patients, one azoospermic and one oligozoospermic, had a high percentage of asynapsed nuclei (86 and 91.8% respectively); one of these patients also presented a precocious localized separation of sister chromatids. CONCLUSION: high levels of extended asynapsis could arise from a primary meiotic defect which may be responsible for 9% of the NO male infertilities at our centre. The prevalence of early pachytene substages suggests that the pachytene checkpoint is localized at the mid-pachytene stage in humans.

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

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

[Pregnancy outcome and the status of the newborn infant after ICSI at La Conception Hospital in Marseille]. / Evolution des grossesses et état des enfants à la naissance après ICSI à l'hôpital de La Conception à Marseille.

OBJECTIVE: To evaluate obstetric outcome of pregnancies and pediatric follow-up of children born after ICSI procedure. MATERIAL AND METHOD: Prospective study from october 1994 to September 1998 in medical assisted procreations center in La Conception hospital in Marseilles. Three hundred forty-two couples undergoing ICSI procedures. INTERVENTIONS: analysis of pregnancy rates, prematurity rates, obstetric outcome and frequency of congenital malformations. RESULTS: One hundred seventy-eight pregnancies have been obtained with 111 children. Multiple pregnancy rate arise 29.7%. The average term at birth in the singleton pregnancies (38.7 weeks) is higher than in the twins (35.7 weeks). The prematurity rate of delivery before 35 weeks of gestation is about 9.6%. Seven of 111 neonates was born with a congenital malformation, no cardiovascular one. One of boys presents a bilateral cryptorchidism with severe bilateral hypotrophy. CONCLUSIONS: Our results are similar with those of others teams. Congenital malformation rates is near rates reported in others studies. However, no bilateral cryptorchidism with bilateral severe hypotrophy has been yet reported in literature.

[Morphological aspect of embryos obtained after fertilization in vitro for male factor or ICSI]. / Aspect morphologique des embryons obtenus après une fécondation in vitro pour indication masculine ou ICSI.

OBJECTIVE: In order to study the eventual impact on fertilization and embryo characteristics of the microinjection procedure we compared the quality of the embryos obtained by ICSI with those of in vitro fertilization with male factors (MF IVF). MATERIAL AND METHODS: One hundred thirty-four cycles of IVF treatment (group 1) were selected with oligoasthenozoospermia according to WHO criteria with a total number of motile spermatozoa between 500,000 and 1 million. One thousand eighty-eight mature oocytes and 486 embryos were obtained. One hundred forty-three cycles of intracytoplasmic sperm injection (group 2) were performed in couples whose in vitro fertilization was imparticable because of extreme sperm impairment. One thousand one hundred forty-seven mature oocytes were injected and 626 embryos were obtained. RESULTS: In group 1, the pregnancy rate per embryo transfer and the implantation rate were respectively 22.7% and 12.3%. In group 2, the pregnancy rate per embryo transfer was 37.1% and the implantation rate was 17%. The statistical analysis of the embryos obtained in the two different groups did not demonstrate any difference in the distribution of the more regular and less fragmented embryos (group A) and those of the more irregular and fragmented embryos (group B). No statistical difference was demonstrated in the chronology of the division of these embryos (groups 1 and 2). CONCLUSION: The pregnancy rate by cycle and by transfer reported by ICSI (p < 0.003 and p < 0.015 respectively) could be related to a significantly higher mean number of transferred embryos (2.65 vs 2.02) in probable relation with a higher cleavage rate (p < 0.00001).

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

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

[Quality of embryos in unexplained sterility]. / Qualité des embryons dans les stérilités inexpliquées.

In our study, the rate of pregnancy by transfer and puncture was not significantly different in unexplained and in tubal infertility, but the mean number of transferred embryos was significantly higher in the first group. To explain these data, we compared the quality of embryos in 32 punctures realized among 29 women with unexplained infertility and in 171 punctures planned among 156 women with tubal infertility. The percentage of embryos with 4 or more blastomeres was significantly lower in the unexplained infertility group than in the pure tubal infertility group.