[Fertility preservation in women affected by a gynecologic carcinoma]. / Préservation de la ­fertilité chez les patientes présentant un ­cancer ­gynécologique.

Gynecological cancers quite often affect young women who wish to preserve their fertility. In addition, with the advancement in age of first pregnancies, this problem has currently taken on a significant scale. Most often, fertility preservation is possible provided that the cancerous tumor is discovered at an early stage and of a non-aggressive histological nature. For uterine cancers (cervix and endometrium), surgery preserving uterine function (associated with hormone therapy for endometrial cancers) is often possible for early tumor stages. For ovarian cancers, indications for fertility preservation are rare and reserved for certain histological types, mainly borderline tumors.

Les cancers gynécologiques touchent assez souvent des femmes jeunes qui souhaitent préserver leur fertilité. De plus, avec l'avancement en âge des premières grossesses, cette problé­matique a pris actuellement une ampleur non négligeable. Le plus souvent une préservation de la fertilité est possible à la condition que la tumeur cancéreuse soit découverte à un stade précoce et de nature histologique peu agressive. Pour les ­cancers de l'utérus (col et endomètre), une chirurgie préservant la fonction utérine (associée à une hormonothérapie pour les cancers endométriaux) est souvent possible pour les stades ­tumoraux débutants. Pour les cancers ovariens, les indications de préser­vation de la fertilité sont rares et réservées à certains types ­histologiques dont essentiellement les tumeurs ­borderline.

[Hematological workup in cases of recurrent early miscarriages: what evidences?] / Bilan hématologique en cas de fausses couches précoces à répétition : quelles évidences ?

Recurrent miscarriages have a major psychological and somatic impact, as well as a significant economic burden. An etiological work-up should be offered after two or three miscarriages, the threshold varying from one scientific society to another. However, the proposed biological work-up must be justified by scientific evidence. A simple blood count, basic coagulation tests including fibrinogen assay and anti-phospholipid antibodies testing should be performed initially. Hereditary thrombophilia testing should only be carried out if there is a history of maternal thrombosis. In the event of an abnormality, management should be multidisciplinary, and the prescription of medication should follow recommended guidelines. Prophylactic treatment is not justified in the absence of a known etiology.

Les fausses couches précoces (FCP) à répétition ont un impact psychologique et somatique important, ainsi qu'un poids économique non négligeable. Un bilan étiologique devrait être proposé à partir de deux ou trois fausses couches, le seuil variant selon les sociétés savantes. Cependant, le bilan biologique doit être justifié par des évidences scientifiques. Une formule sanguine simple, des tests de coagulation de base avec le dosage du fibrinogène et une recherche d'anticorps anti-phospholipides devraient être réalisés en première intention. Une recherche de thrombophilie héréditaire ne devrait être effectuée qu'en cas d'antécédent thrombotique maternel. En cas d'anomalie, la prise en charge doit être multidisciplinaire et la prescription de médicaments doit suivre les recommandations. Un traitement prophylactique n'est pas justifié en l'absence d'étiologie retrouvée.

[Vaginal microbiota and vaginosis]. / Microbiote vaginal et vaginose.

The vaginal microbiota is essentially composed of bacteria of the Lactobacillus genus. These bacteria, by their presence, prevent vaginal contamination by other potentially aggressive germs. Disturbances of the microbiota lead to a pathological state called dysbiosis, one of the most frequent pathogenic aspects of which is bacterial vaginosis. This vaginal state results in nauseating leucorrhoea induced by the proliferation of aero-anaerobic bacteria. Bacterial vaginosis is a source of different clinical impacts: increased risk of genital infection with many pathogens, loss of chance in medically assisted procreation, increased risk of premature delivery. The treatment of bacterial vaginosis must take into account the restitution of a normal microbiota.

Le microbiote vaginal est composé de bactéries du genre Lactobacillus. Ces bactéries empêchent la contamination vaginale par d'autres germes potentiellement agressifs. Les perturbations du microbiote aboutissent à un état pathologique dénommé dysbiose, dont un des aspects pathogènes le plus fréquent est la vaginose bactérienne (VB). La VB se traduit par des leucorrhées nauséabondes induites par la prolifération de bactéries aéro-anaérobies. La VB est source de différents impacts cliniques : majoration du risque infectieux génital, pertes de chance en procréation médicalement assistée, accroissement du risque d'accouchement prématuré… Le traitement de la VB doit prendre en compte la restitution d'un microbiote normal.

[Assisted reproductive technology : strategies of elective single embryo transfer]. / Procréation médicalement assistée : stratégies de transfert électif d'un seul embryon.

The development of assisted reproductive technology (ART) has led to the birth of nearly 6 million children since the first IVF baby in 1978. For many years, it was routine practice to transfer multiple embryos in order to obtain the highest pregnancy rates. This strategy has induced a dramatic increase in multiple pregnancies and the associated complications for the mother and the child. Following better awareness of these issues, ART specialists have tried to reduce multiple pregnancy rates with the goal of producing a single, healthy full term baby. Improvement in embryo culture and cryopreservation are the key factors leading to the strategy of elective single embryo transfer (eSET) which represents the best option to achieving this goal. However eSET strategy needs to be implemented in good prognosis patient with good quality embryos.

Le développement des techniques de procréation médicalement assistée (PMA) a permis la naissance de presque 6 millions d'enfants depuis le premier bébé né par FIV en 1978. Pendant de nombreuses années, le transfert de plusieurs embryons était réalisé de routine afin d'obtenir les meilleurs taux de grossesses. Cette pratique a abouti à une augmentation inquiétante des grossesses multiples et des complications associées pour la mère et l'enfant. Les acteurs de la PMA ont alors eu comme but la naissance à terme d'un enfant en bonne santé. Les techniques de culture et de cryoconservation d'embryons ont permis de développer des stratégies de transfert électif d'un seul embryon (eSET). Toutefois, pour ne pas diminuer les chances de grossesses, l'eSET doit être utilisé chez des patientes à bon pronostic et avec des embryons de bonne qualité.

[Osteoporosis in menopausal women between 40 and 65 years old : an algorithm for the gynaecologist]. / Ostéoporose chez les femmes ménopausées entre 40 et 65 ans : algorithme pour le gynécologue.

Osteoporosis is a bone disease that promotes the development of fragility fractures. An algorithm is proposed for the gynaecologists'use to diagnose and treat osteoporosis in young menopausal women. The fracture risk can be calculated with the FRAX tool. If the 10-year fracture risk is ≥ 10 %, a bone densitometry is recommended, and the result is integrated in the FRAX tool. If the risk is between 10 and 20 %, a treatment should be discussed individually and, in some cases, a pharmacologic preventive treatment, by menopause hormonal treatment or SERMs, can be initiated. A pharmacologic treatment (bisphosphonates or dénosumab) is recommended in case of previous fragility fracture or risk ≥ 20 %, independently of a T-score < -2.5 DS. Patients have to be referred in case of treatment failure or intolerance, and at the end of any denosumab therapy.

L'ostéoporose est une maladie de l'os favorisant des fractures de fragilité. L'algorithme proposé est destiné aux gynécologues pour le diagnostic et le traitement de l'ostéoporose chez la jeune femme ménopausée. L'outil FRAX permet de calculer le risque fracturaire ; si le risque est ≥ 10 % sur dix ans, une densitométrie osseuse est recommandée et le résultat sera intégré dans l'outil FRAX. Si le risque est entre 10­20 %, un traitement peut être discuté et, dans certains cas, on proposera une prévention par traitement hormonal de la ménopause ou par un SERM. Un traitement pharmacologique (bisphosphonates ou dénosumab) est recommandé en présence d'antécédent de fracture de fragilité, ou de risque ≥ 20 %, indépendamment d'un T-score < ­2,5 DS. Il faut référer les patientes en cas d'échec ou intolérance au traitement, et à la fin de tout traitement par dénosumab.

Vitrification of human blastocysts for couples undergoing assisted reproduction: an updated review.

Over the past 40 years there has been a worldwide critical change in the field of assisted reproduction technology (ART), leading to the increased application of single blastocyst transfer, which is extremely important to avoid the risks of multiple pregnancy and associated complications for both mother and babies. Indeed, advancements in ART over the last few decades have been obtained thanks to several improvements, including ovarian stimulation, embryo culture conditions and, of course, progress in cryopreservation methods, especially with the application of vitrification. The ability to cryopreserve human embryos has improved significantly with vitrification compared to the initially adopted slow-freezing procedures. Since the introduction of vitrification, it has become the gold standard method to effectively cryopreserve human blastocysts. However, some new protocols are now being explored, such as the short warming procedure and even shorter exposure to the equilibration solution before vitrification, which seem to provide optimal results. Therefore, the main aim of the current narrative review, will be to illustrate the benefit of vitrification as an effective method to cryopreserve the human blastocyst and to illustrate new protocols and variations which in future may increase the performance of vitrification protocols.

Utero-ovarian transposition before pelvic radiation in a patient with rectal cancer: a case report and systemic literature review.

Objective: To describe a case of utero-ovarian transposition (UOT) before pelvic radiation in a patient with rectal cancer and provide a systematic literature review on all reported cases of UOT. Methods: We performed a prospective collection and revision of clinical, intraoperative, and postoperative data from a patient who underwent UOT. In addition, a systematic review of the literature available to date on all cases of UOT was realized, and 14 patients from 10 articles were included. Results: We reported the case of a 28-year-old nulligravida patient who was diagnosed with a low-grade rectal adenocarcinoma and underwent neoadjuvant chemoradiotherapy, followed by transanal total mesorectal excision (TaTME). Before starting neoadjuvant oncological therapies, the patient underwent laparoscopic UOT. The intervention was performed without complications, and the patient received neoadjuvant oncological treatments as planned. TaTME and uterus repositioning were completed six weeks after the end of radiotherapy. No complications were observed during the first 9 postoperative months. Adequate utero-ovarian perfusion was assessed by Doppler ultrasound, cervicovaginal anastomosis appeared to have healed correctly, and the patient experienced menstrual bleeding. Data from the literature review of all reported cases of UOT were presented and discussed. Conclusions: UOT represents a valuable option to preserve fertility in patients requiring pelvic radiotherapy. This study provides additional evidence on the feasibility and safety of performing UOT.

Effectiveness of degradable polymer film in the management of severe or moderate intrauterine adhesions (PREG-2): a randomized, double-blind, multicenter, stratified, superiority trial.

OBJECTIVE: To study the effectiveness of a new intrauterine degradable polymer film (Womed Leaf) in the management of moderate to severe intrauterine adhesions (IUA). DESIGN: PREG-2 study was a multicenter, double-blind, randomized, controlled, stratified, two-arm superiority clinical trial conducted in 16 centers in seven countries. SETTING: Not applicable. PATIENT(S): Patients ≥18 years scheduled for hysteroscopic adhesiolysis because of symptomatic severe or moderate adhesions (according to American Fertility Society [AFS] IUA score) were considered eligible for the study. INTERVENTION(S): After adhesiolysis, patients were randomized at a 1:1 ratio to either have a Womed Leaf film inserted (intervention group) or not (control group). MAIN OUTCOME MEASURE(S): The primary effectiveness endpoint of the study was the change in AFS IUA score on second-look hysteroscopy (SLH), assessed by an independent evaluator, and compared with baseline. Information on the rate of no IUA and responder rate was collected as secondary effectiveness outcomes, while reported adverse events and patient-reported outcomes as safety and tolerability measures. RESULT(S): Between October 26, 2021, and September 28, 2023, a total of 160 women were randomized (Womed Leaf: n = 75 and controls: n = 85). The reduction in IUA AFS score on SLH was significantly higher in the intervention compared with the control group (mean 5.2 ± 2.8 vs. 4.2 ± 3.2). Similarly, the absence of adhesions on SLH was significantly higher in the intervention group (41% vs. 24%; odds ratio, 2.44; confidence interval, 1.161-5.116). None of the reported adverse events were serious or considered related to the device. CONCLUSION(S): Womed Leaf is effective and safe in the management of symptomatic severe or moderate IUAs. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov identifier: NCT04963179.

Testicular tissue cryopreservation for fertility preservation in prepubertal and adolescent boys: A 6 year experience from a Swiss multi-center network.

Testicular tissue cryopreservation is the only option of fertility preservation in prepubertal boys. While it is considered experimental, since procedures to obtain mature spermatozoa from prepubertal testicular tissue are still under development, testicular tissue cryopreservation programs have emerged worldwide. Our aim was to study the feasibility and safety of a program of testicular tissue cryopreservation in prepubertal and adolescent boys facing gonadotoxic treatment in three University hospitals in Switzerland. Testicular tissue cryopreservation was accepted by 90% of families, with a total of 35 patients included. The average patient age was 8.5 years (range 7 months to 18.5 years). Malignancies were the most common diagnosis (31 patients, 88.6%) with 16 (45.7%) solid tumors and 15 (42.9%) hematological malignancies. Four (11.4%) patients had a benign condition. The main indication for testicular tissue cryopreservation was conditioning for hematologic stem cell transplantation (25 patients, 71.4%). Testicular tissue was cryopreserved according to the freezing protocol of Louvain Catholic University (Belgium), which includes either only immature testicular tissue freezing, or mature and immature testicular tissue freezing depending on the age of the patient and the presence or absence of haploid cells. The median number of spermatogonia per tubule cross-section was 2 (range 0-6) and spermatozoa were found in only one patient. Tumoral cells were found in one testicular biopsy of a leukemic patient. There were two minor adverse events and none of them required medical treatment or surgical revision. Five patients died during follow-up. Our data demonstrate the feasibility and safety of a program of testicular tissue cryopreservation coordinated by a multidisciplinary team of fertility preservation. Despite the experimental aspect of the procedure, the acceptation rate was high, which highlights the willingness of families and patients to participate in testicular tissue cryopreservation.

Interstitial pregnancies' diagnosis and management: an eleven cases series.

PRINCIPLES: Interstitial pregnancy represents 2% of ectopic pregnancies, but it is a highly morbid condition with a 2.5% of maternal mortality. Its diagnostic and therapeutic management remains controversial. The aim of this review is to describe the management of interstitial pregnancy in our institution between 2001 and 2011 and to define some general rules for the clinical practice. METHODS: Single institution retrospective study. RESULTS: Eleven women were treated for interstitial pregnancy. The median age was 33 years and the median gestity was 4. Seven patients had a history of gynaecological surgery and four interstitial pregnancies followed in vitro fertilisation. The diagnosis was made at a median gestational age of seven weeks with a median beta-HCG level of 5,838 U/l. Six of the eleven patients received an initial treatment with intracornual methotrexate, three with intramuscular methotrexate and two with surgery. The median time to beta-HCG resolution was 58 days. Three of the eleven patients needed a second line treatment: two after intramuscular methotrexate and one after intracornual methotrexate. Six patients had further pregnancies and delivered by caesarean section. CONCLUSIONS: A high prevalence of previous ectopic pregnancies, gynaecological surgery and of pregnancies resulting from in vitro fertilisation was observed. The earliness of the diagnosis was the factor that allowed a conservative treatment in most cases. Beta-HCG level follow up was fundamental in allowing a second line therapy but beta-HCG can persist over a long period of time and this must be taken into account due to its possible psychological impact. Intracornual methotrexate seems to be more efficacious than intramuscular methotrexate in our series.

Daily administration of low molecular weight heparin increases Hepatocyte Growth Factor serum levels in gynaecological patients: pharmacokinetic parameters and clinical implications.

BACKGROUND: Hepatocyte Growth Factor (HGF) enhances cytotoxicity of paclitaxel (PTX) and cisplatin (CDDP) in human ovarian cancer cells. Because of potential pitfalls of HGF exogenous administration, we investigated whether HGF serum concentration might be alternatively raised in vivo by administering low molecular weight heparin (LMWH). METHODS: The main HGF pharmacokinetic parameters were evaluated following acute and chronic LMWH treatment. First, women, operated on for gynaecological tumors, were treated with a single dose of calcium nadroparin and studied for 12 hours. Next, women operated on for benign or malignant gynaecological tumors were treated daily with calcic nadroparin for one month. Subsequently, the biological activity of the measured HGF serum levels was tested in assays of ovarian cancer cell sensitization to drugs. RESULTS: In the short-term treated group, median HGF AUCss, Cmax and Caverage were about four-fold that of the control group, whereas Cmin was three-fold. In the patients treated chronically median HGF serum levels rose about six-fold in the first week, and decreased but remained significantly higher after one month. The pharmacokinetic of nadroparin-dependent HGF increase were similar in the two groups. The HGF concentrations measured after both acute and chronic treatment were found to be effective in sensitising ovarian cancer cells to chemotherapeutics. CONCLUSIONS: This study raises the possibility of using LMWH to increase HGF serum concentration and to take advantage of its biological activities. In particular, nadroparin might be used as a chemo-potentiating agent in epithelial cell ovarian carcinoma through its action on HGF serum concentration. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01523652.