Chemotherapy to treat cancer is usually responsible for early ovarian follicle depletion. Ovarian damage induced by cancer treatments frequently results in infertility in surviving patients of childbearing age. Several fertility preservation techniques have been developed. Nowadays, oocyte or embryo cryopreservation with or without ovarian stimulation and cryopreservation of the ovarian cortex are the most commonly used. However, these methods may be difficult to implement in some situations, and subsequent use of the cryopreserved germ cells remains uncertain, with no guarantee of pregnancy. Improved knowledge of the molecular mechanisms and signaling pathways involved in chemotherapy-induced ovarian damage is therefore necessary, to develop new strategies for fertility preservation. The effects of various chemotherapies have been studied in animal models or in vitro on ovarian cultures, suggesting various mechanisms of gonadotoxicity. Today the challenge is to develop molecules and techniques to limit the negative impact of chemotherapy on the ovaries, using experimental models, especially in animals. In this review, the various theories concerning ovarian damage induced by chemotherapy will be reviewed and emerging approaches for ovarian protection will be explained.

When to Stop Contraception - Reasons and Consequences of Delaying Parenthood Abstract. Women are delaying motherhood for many reasons. However, knowledge on age-related decline of fertility is limited. Many patients and even physicians are not aware that female fertility starts to diminish significantly after the age of thirty-two years, and success rates of in vitro treatment are overestimated in the general population. Apart from maternal age there is no predictor for future fecundity. Physicians should actively discuss reasons for delaying motherhood and options for improving fecundity. During the reproductive life span, women need reliable counselling on contraception and fertility.
Zusammenfassung. Die Anzahl Frauen, die gewollt oder ungewollt kinderlos bleiben, nimmt zu. Die Ursachen sind vielfältig. Das Wissen um die physiologische Abnahme der Fruchtbarkeit mit dem Alter ist begrenzt. Die Tatsache, dass die Fruchtbarkeit bereits ab dem 32. Lebensjahr signifikant abnimmt, ist vielen Frauen und auch manchen Ärztinnen und Ärzten nicht bewusst, und die Effizienz der In-vitro-Techniken wird überschätzt. Abgesehen vom Alter gibt es bisher keinen Prädiktor der zukünftigen Fekundität. Ärztinnen und Ärzte sollten sich bei der Diskussion über gesellschaftliche Einflüsse betreffend Alter der Mutter bei der ersten Geburt und den Umgang damit engagiert einbringen. Unsere Patientinnen brauchen nicht nur eine verlässliche Kontrazeptions- sondern auch eine verlässliche Fertilitätsberatung.

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Surgical management of ovarian endometrioma is most often part of a global approach of endometriosis pathology. Isolated endometrioma are rare. Laparoscopic cystectomy is the gold standard for surgical management of endometrioma. Nevertheless, this technique impacts the ovarian function. The hemostasis of the ovarian cyst bed should be performed to conserve the ovarian stroma. Ultrasonography-guided cyst aspiration, laparoscopic drainage and simple bipolar coagulation are not recommended as first line of treatment. Based on the actual literature, we cannot state the place of laser-vaporization and plasma-energy ablation in surgical management. Ethanol sclerotherapy could be an alternative to treat recurrent endometrioma. Uncompleted surgical removal of endometriosis lesions increases the recurrence rate. Endometriosis management should take into account the research and treatment of all the pelvic lesion, especially before surgical management of endometrioma. In this context, the evaluation of ovarian reserve could be useful before surgery.

OBJECTIVE: To compare ovarian function before and after laparoscopic hysterectomy with bilateral salpingectomy for benign lesions with two different systems of haemostasis.
METHODS: In this prospective randomized study comparing two types of energy used for coagulation in bilateral salpingectomy (group A: bipolar electric energy, versus group B: ultrasonic advanced energy [Harmonic®]), forty consecutive non-menopausal patients undergoing laparoscopic hysterectomy for benign lesions were included. Values of anti-Müllerian hormone (AMH), LH and FSH, antral follicle count (AFC) and ovarian vascularization on bilateral Doppler ultrasound, quality of life (questionnaire) were assessed preoperatively and at 1 and 3 months postoperatively.
RESULTS: Preliminary analysis showed shorter salpingectomy operating time (P<0.0001) and less bleeding (P<0.005) in group B. In group A, there was no statistical difference except a decrease in AFC at 1 and 3 months on the right ovary (P=0.04). In group B, AMH levels were significantly lower postoperatively at 3 months and LH levels were increased at 3 months (respectively P=0.02 et P=0.04). There was no statistical difference in the ultrasonographic data. Quality of life did not significantly differ in both groups.
CONCLUSIONS: Preliminary findings showed reduced AMH levels at 3months postoperatively in ultrasonic energy group whereas there was no significative menopausal symptoms. It seems important to continue this study in order to know the real effects of both energy systems on the ovarian function.

Should all women with BRCA1 or BRCA2 genes mutations be considered at risk of prematurely impaired fertility, and thus should a fertility preservation systematically be proposed? Women carrying mutations of BRCA1 or BRCA2 are at high risk for breast and tubo-ovarian cancer. The treatment of a breast cancer at a young age, unrare in this population, is associated with a risk of infertility, due to the ovarian toxicity of chemotherapy, to the recommended duration of hormonotherapy when indicated, and to the time advised before starting a pregnancy. Furthermore, some data in the literature suggest a higher risk of premature ovarian failure among women with BRCA1/2 mutation: advance of the age at menopause and poorer response to ovarian stimulation have been observed. Several pathophysiological hypotheses support this finding, as the involvement of the BRCA genes in maintaining telomere length, the DNA repair anomalies promoting oocyte apoptosis, differences in FMR1 genotype. Current fertility preservation techniques have limitations, some of them being specific to BRCA1/2 women: absence of oncological risk due to stimulation in BRCA1/2 women not clearly demonstrated, oocyte vitrification techniques limited rentability, graft of ovarian cortex not suitable in these women at high risk. Thus, data on the increased risk of premature ovarian failure remaining weak, such a systematic proposal seems questionable.

Circulating nucleic acids (cell-free DNA and microRNAs) have for particularity to be easily detectable in the biological fluids of the body. Therefore, they constitute biomarkers of interest in female and male infertility care. Indeed, in female, they can be used to detect ovarian reserve disorders (polycystic ovary syndrome and low functional ovarian reserve) as well as to assess follicular microenvironment quality. Moreover, in men, their expression levels can vary in case of spermatogenesis abnormalities. Finally, circulating nucleic acids have also the ability to predict successfully the quality of in vitro embryo development. Their multiple contributions during assisted reproductive technology (ART) make of them biomarkers of interest, for the development of new diagnostic and/or prognostic tests, applied to our specialty. Circulating nucleic acids would so offer the possibility of personalized medical care for infertile couples in ART.

OBJECTIVE: To assess midwifery students\' knowledge in the field of female fertility and to study their decision if they had diagnosis of diminished ovarian reserve (DOR).
METHODS: A prospective observational study by self-administered questionnaire was conducted among female midwifery students of seven French schools from June to December 2013. The questionnaire had three parts: (1) questions designed to gather information on the study population; (2) a questionnaire consisting of 10 items to test knowledge about female fertility and ovarian reserve; (3) a self-administered questionnaire simulating a DOR diagnosis and quantifying the decision that students would make using a Likert scale of 5 points.
RESULTS: The participation rate was 72.5% (n=285/393). The average age was 22, 6 years±1.9. Among the 285 participants, the ovarian reserve concept was known by 93% of them (n=265) thanks to the midwifery studies (77%, n=204), the media (9%, n=24) and other sources of information. In total, 83.5% of midwifery students (n=238) were interested in assessing their ovarian reserve, and 48.3% of them were interested in evaluating it immediately (n=115). Among midwifery students, 22.5% of them (n=64) reported that female fertility began to decline from the age of 35 years old; 85.6% (n=244) thought that in vitro fertilization allowed women to conceive if fertility is related to a diminished ovarian reserve; 43.9% (n=125) answered that physical activity and a healthy diet had a beneficial effect on the ovarian reserve. If a DOR was diagnosed to them, 76.8% of students (n=219) would be likely to conceive their first child earlier than expected. Among them, 57.9% (n=165) would agree to have oocyte freezing in this context.
CONCLUSIONS: This study is the first in France that assessed students\' knowledge on fertility. We observed: (1) gaps and misconceptions about female fertility despite a medical training in midwifery students; (2) a belief that in vitro fertilization is effective to overcome infertility related to age; (3) that some of these young students would be favorable to oocyte social freezing (technique not allowed in France); (4) that an adequate information on the decrease of fertility with age could lead some students to anticipate their first pregnancy. Specific information regarding the decrease of fertility with age should be offered to all reproductive-aged young women.

OBJECTIVE: To establish recommendations for early recurrent miscarriages (≥3 miscarriages before 14weeks of amenorrhea).
METHODS: Literature review, establishing levels of evidence and recommendations for grades of clinical practice.
RESULTS: Women evaluation includes the search for a diabetes (grade A), an antiphospholipid syndrome (APS) (grade A), a thyroid dysfunction (grade A), a hyperprolactinemia (grade B), a vitamin deficiency and a hyperhomocysteinemia (grade C), a uterine abnormality (grade C), an altered ovarian reserve (grade C), and a couple chromosome analysis (grade A). For unexplained early recurrent miscarriages, treatment includes folic acid and progesterone supplementation, and a reinsurance policy in the first quarter (grade C). It is recommended to prescribe the combination of aspirin and low-molecular-weight heparin when APS (grade A), glycemic control in diabetes (grade A), L-Thyroxine in case of hypothyroidism (grade A) or the presence of thyroid antibodies (grade B), bromocriptine if hyperprolactinemia (grade B), a substitution for vitamin deficiency or hyperhomocysteinemia (grade C), sectionning a uterine septum (grade C) and treating an uterine acquired abnormality (grade C).
CONCLUSIONS: These recommendations should improve the management of couples faced with early recurrent miscarriages.

During the last years, the use of circulating nucleic acids (microRNAs and cell-free DNA) as diagnostic and/or prognostic tools in cancerology was widely documented. Likewise, in obstetrics and gynecology, the development of non-invasive prenatal testing based on the assessment of these biomarkers confirmed their growing interest in this speciality. In human reproduction, several studies were interested in the microRNAs, small non-coding RNA sequences, present in the ovarian follicle and their implication in folliculogenesis. Some of these microRNAs, as well as the vesicles which transport them, are easily detectable in the bloodstream and could be used as reliable biomarkers of interest in infertility care. Cell-free DNA level varies according to physiopathology and reflect the proportion of apoptotic and/or necrotic events occurring in the body. As a result, its quantification could give an additional help to the practitioners for ovarian functional status evaluation. Furthermore, these circulating nucleic acids could also constitute new predictive biomarkers of oocyte and/or embryo quality and represent a promising perspective for the prevention of in vitro fertilization implantation failures. In conclusion, these circulating nucleic acids open the way to the development of new diagnostic and/or prognostic innovative tests in order to improve in vitro fertilization outcomes.