Introduction La préservation de la fertilité (PF) a été développée pour les patientes atteintes de cancer devant recevoir un traitement potentiellement délétère pour la fonction ovarienne. Ses ...indications se sont élargies à toute femme dont la « fertilité risque d’être prématurément altérée ». Une mutation du gène FMR1 (sur le chromosome X) est la première cause génétique de retard mental chez le garçon. Une pré-mutation de ce gène est à l’origine d’une augmentation du risque d’insuffisance ovarienne primaire. Ainsi, les femmes jeunes pré-mutées doivent être informées de l’altération potentiellement prématurée de leur fertilité, et deviennent candidates à une PF. Par ailleurs, devant le risque de transmission à la descendance, un diagnostic prénatal (DPN) ou pré-implantatoire (DPI) peut aussi leur être proposé. Observation Nous rapportons une mini-série de 6 patientes, entre 19 et 36 ans, porteuses d’une pré-mutation FMR1 , ayant bénéficié d’une PF par stimulation de l’ovulation suivie d’une vitrification des ovocytes matures obtenus. Ces patientes ont pu bénéficier de 1 à 3 cycles de stimulation permettant de congeler en moyenne 12,8 ± 9 ovocytes matures au total. Discussion Une pré-mutation FMR1 est une nouvelle indication de PF posant également un problème éthique lié au risque de transmission. L’indication de DPN ou de DPI doit être discutée avec la patiente avant la prise en charge. Le DPI nécessitant un nombre d’ovocytes matures important, il est souvent nécessaire de réaliser plusieurs cycles de stimulation afin de congeler le maximum d’ovocytes matures. D’autres alternatives, comme le don d’ovocytes ou l’adoption doivent également être abordées.
Human embryo culture under 2-8% O2 is recommended by ESHRE revised guidelines for good practices in IVF labs. Nevertheless, notably due to the higher costs of embryo culture under hypoxia, some ...laboratories perform embryo culture under atmospheric O2 tension (around 20%). Furthermore, recent meta-analyses concluded with low evidence to a superiority of hypoxia on IVF/ICSI outcomes. Interestingly, a study on mice embryos suggested that oxidative stress (OS) might only have an adverse impact on embryos at cleavage stage. Hence, we aimed to demonstrate for the first time in human embryos that OS has a negative impact only at cleavage stage and that sequential culture conditions (5% O2 from Day 0 to Day 2/3, then «conventional» conditions at 20% O2 until blastocyst stage) might be a valuable option for human embryo culture. 773 IVF/ICSI cycles were included in this randomized clinical trial from January 2016 to April 2018. At Day 0 (D0), patients were randomized using a 1:2 allocation ratio between group A (20% O2; n = 265) and group B (5% O2; n = 508). Extended culture (EC) was performed when ≥ 5 Day 2-good-quality-embryos were available (n = 88 in group A (20% O2)). In subgroup B, 195 EC cycles were randomized again at Day 2 (using 1:1 ratio) into groups B' (5% O2 until Day 6 (n = 101)) or C (switch to 20% O2 from Day 2 to Day 6 (n = 94). Fertilization rate, cleavage-stage quality Day 2-top-quality-embryo (D2-TQE), blastocyst quality (Day 5-top-quality-blastocyst (D5-TQB) and implantation rate (IR) were compared between groups A and B (= cleavage-stage analysis), or A(20% O2), B'(5% O2) and C(5%-to-20% O2). Overall, characteristics were similar between groups A and B. Significantly higher rates of early-cleaved embryos, top-quality and good-quality embryos on Day 2 were obtained in group B compared to group A (P < 0.05). This association between oxygen tension and embryo quality at D2 was confirmed using an adjusted model (P < 0.05). Regarding blastocyst quality, culture under 20% O
from Day 0 to Day 6 (group A) resulted in significantly lower Day 5-TQB number and rates (P < 0.05) compared to both groups B' and C. Furthermore, blastocyst quality was statistically equivalent between groups B' and C (P = 0.45). At Day 6, TQB numbers and rates were also significantly higher in groups B' and C compared to group A (P < 0.05). These results were confirmed analyzing adjusted mean differences for number of Day 5 and Day 6 top quality embryos obtained in group A when compared to those respectively in groups B' and C (P < 0.05). No difference in clinical outcomes following blastocyst transfers was observed. These results would encourage to systematically culture embryos under hypoxia at least during early development stages, since OS might be detrimental exclusively before embryonic genome activation.
BACKGROUND The global obesity epidemic has paralleled a decrease in semen quality. Yet, the association between obesity and sperm parameters remains controversial. The purpose of this report was to ...update the evidence on the association between BMI and sperm count through a systematic review with meta-analysis. METHODS A systematic review of available literature (with no language restriction) was performed to investigate the impact of BMI on sperm count. Relevant studies published until June 2012 were identified from a Pubmed and EMBASE search. We also included unpublished data (n = 717 men) obtained from the Infertility Center of Bondy, France. Abstracts of relevant articles were examined and studies that could be included in this review were retrieved. Authors of relevant studies for the meta-analysis were contacted by email and asked to provide standardized data. RESULTS A total of 21 studies were included in the meta-analysis, resulting in a sample of 13 077 men from the general population and attending fertility clinics. Data were stratified according to the total sperm count as normozoospermia, oligozoospermia and azoospermia. Standardized weighted mean differences in sperm concentration did not differ significantly across BMI categories. There was a J-shaped relationship between BMI categories and risk of oligozoospermia or azoospermia. Compared with men of normal weight, the odds ratio (95% confidence interval) for oligozoospermia or azoospermia was 1.15 (0.93-1.43) for underweight, 1.11 (1.01-1.21) for overweight, 1.28 (1.06-1.55) for obese and 2.04 (1.59-2.62) for morbidly obese men. CONCLUSIONS Overweight and obesity were associated with an increased prevalence of azoospermia or oligozoospermia. The main limitation of this report is that studied populations varied, with men recruited from both the general population and infertile couples. Whether weight normalization could improve sperm parameters should be evaluated further.
Abstract
STUDY QUESTION
What threshold values of ultrasonographic antral follicle count (AFC) and serum anti-Müllerian hormone (AMH) levels should be considered for ensuring the cryopreservation of ...sufficient number of in vitro matured (IVM) oocytes, in cancer patients seeking fertility preservation (FP)?
SUMMARY ANSWER
AFC and serum AMH values >20 follicles and 3.7 ng/ml, respectively, are required for obtaining at least 10 IVM oocytes for cryopreservation.
WHAT IS KNOWN ALREADY
IVM of cumulus oocyte complexes (COCs) followed by oocyte cryopreservation has emerged recently as an option for urgent FP. Recent data have reported that, in healthy patients, 8–20 cryopreserved oocytes after ovarian stimulation would maximize the chance of obtaining a live birth. Although both AFC and AMH have been reported as predictive factors of IVM success in infertile patients with polycystic ovary syndrome (PCOS), there is a dramatic lack of data regarding the values of these parameters in oncological patients as candidates for FP.
STUDY DESIGN, SIZE, DURATION
From January 2009 to April 2015, we prospectively studied 340 cancer patients, aged 18–41 years, as candidates for oocyte cryopreservation following IVM.
PARTICIPANTS/MATERIALS, SETTING, METHODS
All patients had AFC and AMH measurements, 48–72 h before oocyte retrieval, regardless of the phase of the cycle. COCs were recovered under ultrasound guidance 36 h after hCG priming. Logistic regression allowed the determination of threshold values of AFC and AMH, for obtaining at least 8, 10 or 15 matures oocytes frozen after the IVM procedure. Similar analyses were performed for a final number of mature oocytes ≤2.
MAIN RESULTS AND THE ROLE OF CHANCE
Among the 340 cancer patients included, 300 were diagnosed with breast cancers, 14 had hematological malignancies and 26 underwent the procedure for others indications. Overall, the mean age of the population was 31.8 ± 4.5 years. Mean AFC and serum AMH levels were 21.7 ± 13.3 follicles and 4.4 ± 3.8 ng/ml, respectively. IVM was performed in equal proportions during the follicular or luteal phase of the cycle (49 and 51%, respectively). Statistical analysis showed that AFC and AMH values above 28 follicles and 3.9 ng/ml, 20 follicles and 3.7 ng/ml and 19 follicles and 3.5 ng/ml are required, respectively, for obtaining at least 15, 10 or 8 frozen IVM oocytes with a sensitivity ranging from 0.82 to 0.90. On the contrary, ≤2 IVM oocytes were cryopreserved when AFC and AMH were <19 follicles and 3.0 ng/ml, respectively.
LIMITATIONS, REASONS FOR CAUTION
Although the potential of cryopreserved IVM oocytes from cancer patients remains unknown, data obtained from infertile PCOS women have shown a dramatically reduced competence of these oocytes when compared with that of oocytes recovered after ovarian stimulation. As a consequence, the optimal number of IVM oocytes frozen in candidates for FP is currently unpredictable.
WIDER IMPLICATIONS OF THE FINDINGS
Cryopreservation of oocytes after IVM should be considered in the FP strategy when ovarian stimulation is unfeasible, in particular when markers of the follicular ovarian status are at a relatively high range. Further investigation is needed to objectively assess the real potential of these IVM oocytes after cryopreservation. Therefore, even when a good COCs yield is expected, we should systematically encourage IVM in combination with ovarian tissue cryopreservation.
STUDY FUNDING/COMPETING INTEREST(S)
No external funding was obtained for the present study. The authors have no conflict of interest to declare.
TRIAL REGISTRATION NUMBER
Not applicable.
To describe strategy and results of fertility preservation (FP) in patients with malignant and borderline ovarian tumors.
Consecutive cohort study of 43 women with malignant or borderline ovarian ...tumors who underwent FP between February 2013 and July 2019.
The study was conducted in national expert center in Tenon University Hospital, Sorbonne University: French ESGO-certified ovarian cancer center and pregnancy-associated cancer network (CALG). Main outcome measure was FP technique proposed by multidisciplinary committee, FP technique used, time after surgery, number of fragments, histology and follicle density (if ovarian tissue freezing), number of expected, retrieved and frozen oocytes (if ovarian stimulation).
Pathological diagnosis was malignant epithelial ovarian tumor in five women (11.6%), rare malignant ovarian tumor in 14 (32.6%), borderline in 24 (55.8%), and mostly unilateral (79.1%) and stage I (76.7%). Mean age at diagnosis was 26.8 ± 6.9 years and mean tumor size 109.7 ± 61 mm. Before FP, mean AFC was 11.0 ± 6.1 and AMH levels were 2.7 ± 4.6 ng/mL. Six ovarian tissue-freezing procedures were performed (offered to 13). Twenty-four procedures of ovarian stimulation and oocyte freezing were performed after surgical treatment for 19 women (offered to 28) with a median interval of 188 days. The mean number of mature oocytes retrieved per stimulation was 12.4 ± 12.8. At least 10 mature oocytes were frozen for 52.6% of the women. No FP was offered to five women.
Oocyte and ovarian tissue cryopreservation should be offered to patients with malignant and borderline ovarian tumors. More data are needed to confirm ovarian stimulation and ovarian tissue grafting safety.
•The median number of ovarian tissue frozen fragments was 22 per patient•In mature oocyte vitrification after ovarian stimulation ten or more frozen oocytes were obtained in 55.6% patients•Preoperative fertility preservation consultations increased from 0% in 2013 to 67% in 2019•Only 28.6% of the patients declined ovarian stimulation for oocyte cryopreservation
Bien qu’il ait été longtemps ignoré ou peu exprimé, le désir de parentalité est présent chez certaines personnes transgenres. L’évolution des techniques médicales ainsi que les changements ...législatifs permettent actuellement de proposer des stratégies de préservation de la fertilité dans le contexte de transidentité de genre. Lors des parcours de transition « female to male », dit FtM, l’androgénothérapie a un impact sur la fonction gonadique puisqu’elle induit généralement un blocage de l’ovulation avec aménorrhée. Bien que cet effet soit réversible à l’arrêt du traitement, les éventuels effets à long terme du traitement par testostérone sur la fertilité future, voire sur la santé des enfants a naître, ne sont pas bien connus. De plus, les chirurgies de transition compromettent définitivement la possibilité de grossesse lorsqu’elles comprennent une annexectomie bilatérale et/ou une hystérectomie. Les options de préservation de la fertilité dans le cadre d’une transition FtM reposent sur la cryoconservation d’ovocytes ou de tissu ovarien. De la même manière, les traitements hormonaux reçus par les personnes trans male to female (MtF) peuvent avoir un impact sur la fertilité ultérieure même si ceci est encore mal documenté. A fortiori en cas de chirurgie avec orchidectomie bilatérale la fertilité est définitivement impossible s’il n’a pas été réalisé une cryopréservation de spermatozoïdes. Dans les deux cas de nombreux obstacles juridiques et réglementaires s’opposent toutefois à la réutilisation des gamètes cryopréservés dans l’état actuel de la législation. Il est également indispensable d’encadrer ces prises en charge par la proposition d’un soutien psychologique, notamment compte tenu de ces contraintes.
Oftentimes ignored or infrequently expressed, some transgender persons harbor a desire for parenthood. Given the evolution of medical techniques and the enacting of legislative reforms, it is henceforth possible to propose fertility preservation strategies in the overall context of gender transidentity. During the “female to male” (FtM) transition pathway, androgen therapy has an impact on gonadic function, generally inducing blockage of the ovarian function, with amenorrhea. Even though these events may be reversed on cessation of treatment, the possible long-term effects on future fertility and on the health of children yet to be born are little known. Moreover, transition surgeries definitively compromise the possibility of pregnancy insofar as they involve bilateral adnexectomy and/or hysterectomy. Options for fertility preservation in the framework of FtM transition are premised on cryopreservation of oocytes and/or ovarian tissue. In a comparable manner, even though relevant documentation is lacking, hormonal treatments for persons transitioning from male to female (MtF) can have an impact on future fertility. In the event of surgery involving bilateral orchidectomy in which spermatozoid cryopreservation has not been carried out, fertility is definitively impossible. In both cases and under present-day legislation, numerous legal and regulatory barriers render highly problematic the reutilization of cryopreserved gametes. Given these different constraints, it is indispensable to closely supervise these types of treatment by proposing psychological support.
We here report a successful pregnancy and healthy childbirth obtained in a case of total globozoospermia after intracytoplasmic morphologically selected sperm injection (IMSI) without assisted oocyte ...activation (AOA). Two semen analyses showed 100% globozoospermia on classic spermocytogram. Motile sperm organelle morphology examination (MSOME) analysis at ×10 000 magnification confirmed the round-headed aspect for 100% of sperm cells, but 1% of the spermatozoa seemed to present a small bud of acrosome. This particular aspect was confirmed by transmission electron microscopy and anti-CD46 staining analysis. Results from sperm DNA fragmentation and fluorescence in situ hybridization analyses were normal. The karyotype was 46XY, and no mutations or deletions in SPATA16 and DPY19L2 genes were detected. Considering these results, a single IMSI cycle was performed, and spermatozoa were selected for the absence of vacuoles and the presence of a small bud of acrosome. A comparable fertilization rate with or without calcium-ionophore AOA was observed. Two fresh top-quality embryos obtained without AOA were transferred at Day 2 after IMSI, leading to pregnancy and birth of a healthy baby boy. This successful outcome suggests that MSOME may be useful in cases of globozoospermia in order to carefully evaluate sperm morphology and to maximize the benefit of ICSI/IMSI.
Oftentimes ignored or infrequently expressed, some transgender persons harbor a desire for parenthood. Given the evolution of medical techniques and the enacting of legislative reforms, it is ...henceforth possible to propose fertility preservation strategies in the overall context of gender transidentity. During the "female to male" (FtM) transition pathway, androgen therapy has an impact on gonadic function, generally inducing blockage of the ovarian function, with amenorrhea. Even though these events may be reversed on cessation of treatment, the possible long-term effects on future fertility and on the health of children yet to be born are little known. Moreover, transition surgeries definitively compromise the possibility of pregnancy insofar as they involve bilateral adnexectomy and/or hysterectomy. Options for fertility preservation in the framework of FtM transition are premised on cryopreservation of oocytes and/or ovarian tissue. In a comparable manner, even though relevant documentation is lacking, hormonal treatments for persons transitioning from male to female (MtF) can have an impact on future fertility. In the event of surgery involving bilateral orchidectomy in which spermatozoid cryopreservation has not been carried out, fertility is definitively impossible. In both cases and under present-day legislation, numerous legal and regulatory barriers render highly problematic the reutilization of cryopreserved gametes. Given these different constraints, it is indispensable to closely supervise these types of treatment by proposing psychological support.
Résumé
L’impact délétère de l’obésité sur la fertilité féminine est important. L’obésité représente également un facteur de risque de nombreuses complications obstétricales maternelles et fœtales. La ...chirurgie bariatrique a montré une efficacité sur plusieurs comorbidités cardiométaboliques ainsi que sur lamortalité. Ses conséquences sur la fertilité et les complications maternofœtales demeurent par contre controversées. Dans ce contexte, nous avons souhaité évaluer l’impact de la chirurgie bariatrique sur la fertilité et les complications maternofœtales à l’aide d’un questionnaire, posé par entretien téléphonique, sur un échantillon de 191 femmes en âge de procréer (de 18 à 40 ans) ayant subi une chirurgie bariatrique. Les résultats de notre enquête confirment une perte de poids significative et une diminution des comorbidités après chirurgie ainsi qu’une amélioration des troubles du cycle. En revanche, il n’a pas été observé de diminution significative du nombre de fausses couches et des complications maternofœtales.
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