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Stoop D.,Center for Reproductive Medicine | Cobo A.,IVI Valencia | Silber S.,St Lukes Hospital
The Lancet | Year: 2014

Cryopreservation of eggs or ovarian tissue to preserve fertility for patients with cancer has been studied since 1994 with R G Gosden's paper describing restoration of fertility in oophorectomised sheep, and for decades previously by others in smaller mammals. Clinically this approach has shown great success. Many healthy children have been born from eggs cryopreserved with the Kuwayama egg vitrifi cation technique for non-medical (social) indications, but until now very few patients with cancer have achieved pregnancy with cryopreserved eggs. Often, oncologists do not wish to delay cancer treatment while the patient goes through multiple ovarian stimulation cycles to retrieve eggs, and the patient can only start using the oocytes after full recovery from cancer. Ovarian stimulation and egg retrieval is not a barrier for patients without cancer who wish to delay childbearing, which makes oocyte cryopreservation increasingly popular to overcome an age-related decline in fertility. Cryopreservation of ovarian tissue is an option if egg cryopreservation is ruled out. More than 37 babies have been born so far with cryopreserved ovarian tissue in patients with cancer who have had a complete return of hormonal function, and fertility to baseline. Both egg and ovarian tissue cryopreservation might be ready for application to the preservation of fertility not only in patients with cancer but also in countering the increasing incidence of age-related decline in female fertility.

Tournaye H.J.,Center for Reproductive Medicine | Cohlen B.J.,Fertility Center
Best Practice and Research: Clinical Obstetrics and Gynaecology | Year: 2012

For many years, the management of male-factor infertility has been empirical rather than evidence-based. In current clinical practice, assisted reproductive techniques are the most successful methods of alleviating male-factor infertility. To date, it remains unclear what adjuvant actions can be taken to improve the outcome of assisted reproductive techniques for male-factor infertility. Evidence shows that smoking adversely affects sperm quality to some extent, and the genetic make-up of sperm to a greater extent; however, because of the scarcity and heterogeneity of studies, its effect on in-vitro fertilisation outcome remains largely unknown. Although smoking cessation should be part of the assisted reproductive techniques treatment plan, the benefit of antioxidant treatment in either smokers or non-smokers undergoing assisted reproductive techniques is still under scrutiny. Other lifestyle modifications in subfertile men, such as refraining from moderate alcohol and caffeine consumption, are even more controversial. When embarking on assisted reproductive techniques to alleviate male-factor infertility, intrauterine insemination may be considered as a first-line treatment for couples in whom the female partner has a normal fertility status, and at least 0.8 × 106 progressively motile spermatozoa are recovered after sperm preparation. If no pregnancy is achieved after three to six cycles of intrauterine insemination, in-vitro fertilisation can be proposed. When too few progressively motile spermatozoa are obtained after sperm processing for in-vitro fertilisation, or when surgically retrieved sperm are to be used, intracytoplasmic sperm injection is preferable. Although the outcome of no other assisted reproductive techniques has been scrutinised so much, and no large-scale 'macro-problems' have yet been observed after intracytoplasmic sperm injection, malformation rates are reported to be higher compared with the general population. Therefore, candidates for intracytoplasmic sperm injection should be rigorously screened before embarking on in-vitro fertilisation or intracytoplasmic sperm injection, and thoroughly informed of the limitations of our knowledge on the hereditary aspects of male infertility and the safety aspects of assisted reproductive techniques.

De Vos M.,Center for Reproductive Medicine | Devroey P.,Center for Reproductive Medicine | Fauser B.C.,University Utrecht
The Lancet | Year: 2010

Primary ovarian insufficiency is a subclass of ovarian dysfunction in which the cause is within the ovary. In most cases, an unknown mechanism leads to premature exhaustion of the resting pool of primordial follicles. Primary ovarian insufficiency might also result from genetic defects, chemotherapy, radiotherapy, or surgery. The main symptom is absence of regular menstrual cycles, and the diagnosis is confirmed by detection of raised follicle-stimulating hormone and declined oestradiol concentrations in the serum, suggesting a primary ovarian defect. The disorder usually leads to sterility, and has a large effect on reproductive health when it arises at a young age. Fertility-preservation options can be offered to some patients with cancer and those at risk of early menopause, such as those with familial cases of primary ovarian insufficiency. Long-term deprivation of oestrogen has serious implications for female health in general; and for bone density, cardiovascular and neurological systems, wellbeing, and sexual health in particular. © 2010 Elsevier Ltd.

De Vos M.,Center for Reproductive Medicine | Smitz J.,Laboratory of Clinical Chemistry and Radioimmunology | Woodruff T.K.,Northwestern University
The Lancet | Year: 2014

Enhanced long-term survival rates of young women with cancer and advances in reproductive medicine and cryobiology have culminated in an increased interest in fertility preservation methods in girls and young women with cancer. Present data suggest that young patients with cancer should be referred for fertility preservation counselling quickly to help with their coping process. Although the clinical application of novel developments, including oocyte vitrification and oocyte maturation in vitro, has resulted in reasonable success rates in assisted reproduction programmes, experience with these techniques in the setting of fertility preservation is in its infancy. It is hoped that these and other approaches, some of which are still regarded as experimental (eg, ovarian tissue cryopreservation, pharmacological protection against gonadotoxic agents, in-vitro follicle growth, and follicle transplantation) will be optimised and become established within the next decade. Unravelling the complex mechanisms of activation and suppression of follicle growth will not only expand the care of thousands of women diagnosed with cancer, but also inform the care of millions of women confronted with reduced reproductive fitness because of ageing.

Mateizel I.,Center for Reproductive Medicine | Van Landuyt L.,Center for Reproductive Medicine | Tournaye H.,Center for Reproductive Medicine | Verheyen G.,Center for Reproductive Medicine
Human Reproduction | Year: 2013

STUDY QUESTIONShould oocytes showing the presence of smooth endoplasmic reticulum aggregates (SER) be considered for embryo transfer?SUMMARY ANSWERThe present study shows that embryos derived from metaphase II oocyte with visible SER (SER+MII) have the capacity to develop normally and may lead to newborns with no major malformations.WHAT IS KNOWN ALREADYIt has been reported that the presence of SER in the cytoplasm of oocytes has a negative impact on embryo development, and is associated with a decreased clinical outcome and an increased risk of congenital anomalies. Therefore, it has been recommended that embryos derived from SER-positive oocytes should not be transferred.STUDY DESIGN, SIZE, DURATIONConsecutive ICSI cycles with at least one SER+MII oocyte were retrospectively analyzed regarding embryological and pregnancy outcome and compared with ICSI cycles showing only oocytes without SER (SER-MII). PARTICIPANTS/MATERIALS, SETTING, METHODSIn total, 394 SER-positive (SER+) cycles and 6845 SER-negative (SER-) cycles were analyzed. The Student's t-test, one-way analysis of variance test and χ2 test were used for statistical analysis. P value of <0.05 was considered statistically significant.MAIN RESULTS AND THE ROLE OF CHANCEComparable fertilization rates were observed in SER+ (76.2%) and SER- (73.5%) cycles. In case of blastocyst culture, the cycle efficiency was lower in SER+ than in SER- cycles (mean 42.2 versus 62.8%, P < 0.001). The pregnancy and clinical pregnancy (CP) rates per embryo transfer (ET) were comparable for SER+ and SER- cycles (37.6 versus 37.8% and 33.0 versus 32.4%, respectively).In the SER+ cycles, the fertilization rates of SER+MII and SER-MII (72.9 versus 77.0%), as well as the capacity to develop into good-quality embryos on Days 3 (62.3 versus 63.7%) and 5 (45.4 versus 47.4%), were similar. In the 364 SER+ cycles, the ETs were subdivided in: ET with only SER+MII (n = 31; 8.5%), ET with only SER-MII (n = 235; 64.5%) and ET with mixed SER+ and SER-MII (n = 98; 26.9%). The pregnancy (25.8, 37.4 and 41.8%, respectively) and CP rates (22.6, 32.4 and 37.9%, respectively) were not different between the three subgroups. Among the cycles with known outcome, there was no difference in the rate of major malformations between SER+ cycles (5.3%) and SER- cycles (2.1%). Moreover, no major malformations were reported from the live borns definitely originating from SER+MII embryos. In addition, three newborns, from single ET with frozen-thawed embryos originating from SER+MII oocytes, were delivered and presented no major malformation.LIMITATIONS, REASONS FOR CAUTIONTaking into account the previous publications and our neonatal data, a follow-up of the children born after ET with embryos originating from SER+ cycles is encouraged.WIDER IMPLICATION OF THE FINDINGSMore studies should be performed to investigate the origin and effect of SER aggregates on the molecular status of oocytes and embryos.STUDY FUNDING/COMPETING INTEREST(S)No external funding was either sought or obtained for this study and there are no potential competing interests.TRIAL REGISTRATION NUMBERNot applicable. © The Author 2013.

Roque M.,Center for Reproductive Medicine | Esteves S.C.,Center for Male Reproduction
Asian Journal of Andrology | Year: 2016

A systematic review was conducted to identify and qualitatively analyze the methods as well as recommendations of Clinical Practice Guidelines (CPG) and Best Practice Statements (BPS) concerning varicocele in the pediatric and adolescent population. An electronic search was performed with the MEDLINE, EMBASE, Science Direct, and Scielo databases, as well as guidelines′ Web sites until September 2015. Four guidelines were included in the qualitative synthesis. In general, the recommendations provided by the CPG/BPS were consistent despite the existence of some gaps across the studies. The guidelines issued by the American Urological Association (AUA) and American Society for Reproductive Medicine (ASRM) did not provide evidence-based levels for the recommendations given. Most of the recommendations given by the European Association of Urology (EAU) and European Society of Pediatric Urology (ESPU) were derived from nonrandomized clinical trials, retrospective studies, and expert opinion. Among all CPG/BPS, only one was specifically designed for the pediatric population. The studied guidelines did not undertake independent cost-effectiveness and risk-benefit analysis. The main objectives of these guidelines were to translate the best evidence into practice and provide a framework of standardized care while maintaining clinical autonomy and physician judgment. However, the limitations identified in the CPG/BPS for the diagnosis and management of varicocele in children and adolescents indicate ample opportunities for research and future incorporation of higher quality standards in patient care. © 2016 AJA, SIMM & SJTU.

Devroey P.,Center for Reproductive Medicine | Polyzos N.P.,Center for Reproductive Medicine | Blockeel C.,Center for Reproductive Medicine
Human Reproduction | Year: 2011

Published data indicate a significant increase in ovarian hyperstimulation syndrome globally. The occurrence of approximately three maternal deaths per 100 000 stimulated women has been reported, and extrapolation of these figures to a global situation would give an impressive number. The syndrome can be erased by applying ovarian stimulation using the combination of GnRH antagonist with GnRH agonist to trigger ovulation. In this case, the strategy is to freeze all of the oocytes or embryos for later use. © 2011 The Author.

Goossens E.,Vrije Universiteit Brussel | Van Saen D.,Center for Reproductive Medicine | Tournaye H.,Vrije Universiteit Brussel | Tournaye H.,Center for Reproductive Medicine
Human Reproduction | Year: 2013

STUDY QUESTION: What issues remain to be solved before fertility preservation and transplantation can be offered to prepubertal boys? SUMMARY ANSWER: The main issues that need further investigation are malignant cell decontamination, improvement of in vivo fertility restoration and in vitro maturation.WHAT IS KNOWN ALREADYPrepubertal boys who need gonadotoxic treatment might render sterile for the rest of their life. As these boys do not yet produce sperm cells, they cannot benefit from sperm banking. Spermatogonial stem cell (SSC) banking followed by autologous transplantation has been proposed as a fertility preservation strategy. But before this technique can be applied in the clinic, some important issues have to be resolved.STUDY DESIGN, SIZE DURATIONOriginal articles as well as review articles published in English were included in a search of the literature.PARTICIPANTS/MATERIALS, SETTING, METHODSRelevant studies were selected by an extensive Medline search. Search terms were fertility preservation, cryopreservation, prepubertal, SSC, testis tissue, transplantation, grafting and in vitro spermatogenesis. The final number of studies selected for this review was 102. MAIN RESULTS AND THE ROLE OF CHANCE: Cryopreservation protocols for testicular tissue have been developed and are already being used in the clinic. Since the efficiency and safety of SSC transplantation have been reported in mice, transplantation methods are now being adapted to the human testes. Very recently, a few publications reported on in vitro spermatogenesis in mice, but this technique is still far from being applied in a clinical setting. LIMITATIONS, REASONS FOR CAUTION: Using tissue from cancer patients holds a potential risk for contamination of the collected testicular tissue. Therefore, it is of immense importance to separate malignant cells from the cell suspension before transplantation. Because biopsies obtained from young boys are small and contain only few SSCs, propagation of these cells in vitro will be necessary. WIDER IMPLICATIONS OF THE FINDINGS: The ultimate use of the banked tissue will depend on the patient's disease. If the patient was suffering from a non-malignant disease, tissue grafting might be offered. In cancer patients, decontaminated cell suspensions will be injected in the testis. For patients with Klinefelter syndrome, the only option would be in vitro spermatogenesis. However, at present, restoring fertility in cancer and Klinefelter patients is not yet possible. STUDY FUNDING/COMPETING INTEREST(S): Research Foundation, Flanders (G.0385.08 to H.T.), the Institute for the Agency for Innovation, Belgium (IWT/SB/111245 to E.G.), the Flemish League against Cancer (to E.G.), Kom op tegen kanker (G.0547.11 to H.T.) and the Fund Willy Gepts (to HT). E.G. is a Postdoctoral Fellow of the FWO, Research Foundation, Flanders. There are no conflicts of interest. © 2013 The Author.

The introduction of the technique of intracytoplasmic sperm injection to achieve fertilization, especially using surgically retrieved testicular or epididymal sperm from men with obstructive or non-obstructive azoospermia, has revolutionized the field of assisted reproduction. The techniques for the retrieval of spermatozoa vary from relatively simple percutaneous sperm aspiration to open excision (testicular biopsy) and the more invasive Micro-TESE. The probability of retrieving spermatozoa can be as high as 100% in men with obstructive azoospermia (congenital bilateral absence of the vas deferens, status post-vasectomy). However, in nonobstructive azoospermia, successful sperm retrieval has been reported in 10-100% of cases by various investigators. The surgical retrieval and cryopreservation of sperm, especially in men with non-obstructive azoospermia, to some extent ensures the availability of sperm at the time of intracytoplasmic sperm injection. In addition, this strategy can avoid unnecessary ovarian stimulation in those patients intending to undergo in vitro fertilization-intracytoplasmic sperm injection with freshly retrieved testicular sperm when an absolute absence of sperm in the testis is identified. Several different methods for the cryopreservation of testicular and epididymal sperm are available. The choice of the container or carrier may be an important consideration and should take into account the number or concentration of the sperm in the final preparation. When the number of sperm in a testicular biopsy sample is extremely low (e.g., 1-20 total sperm available), the use of an evacuated zona pellucida to store the cryopreserved sperm has been shown to be an effective approach. © 2013 CLINICS.

Roque M.,Center for Reproductive Medicine
Journal of Assisted Reproduction and Genetics | Year: 2015

Purpose: This publication will evaluate the available evidence in the literature comparing fresh embryo transfer (ET) and elective frozen-thawed embryo transfer (FET) regarding the possible interference of controlled ovarian stimulation (COS) in implantation and endometrial receptivity, IVF safety, and obstetric and perinatal outcomes.Methods: We performed a review in the literature of the available evidence comparing fresh to elective FET (freeze-all policy).Results: The improvements made in cryopreservation techniques have led to few or no detrimental effects to the embryo and have resulted in no consequences to the offspring when compared to fresh embryos; this has allowed reproductive practitioners to create the freeze-all policy (when all viable embryos are electively cryopreserved in the fresh cycle and transferred in a posterior cycle). There are increasing concerns about the adverse effects associated with COS over the endometrial and uterine environments, as well as with the safety of COS in pregnancies that have originated from fresh ET during in vitro fertilization (IVF) treatments. COS may contribute to modifications in the endometrium, which might be related to poorer outcomes when fresh ET is performed. It has been suggested that obstetric and perinatal outcomes in pregnancies resulting from fresh ET are poorer when compared with those that occur after FET. In cycles with fresh ET, there is still a risk of ovarian hyperstimulation syndrome (OHSS).Conclusion: There is growing evidence in the literature suggesting better IVF outcomes, and decreased obstetric and perinatal morbidity when adopting the freeze-all policy instead of fresh ET. © 2014, Springer Science+Business Media New York.

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