The case for mild stimulation for IVF: recommendations from The International Society for Mild Approaches in Assisted Reproduction.

The practice of ovarian stimulation for IVF is undergoing a fundamental re-evaluation as recent data begin to successfully challenge the traditional paradigm that ovarian stimulation should be aimed at the retrieval of as many oocytes as possible, in the belief that this will increase pregnancy rates. An opposing view is that live birth rate should not be the only end-point in evaluating the success of IVF treatment and that equal emphasis should be placed on safety and affordability. The International Society for Mild Approaches in Assisted Reproduction (ISMAAR) committee has carried out an up-to-date literature search, with the evidence being graded according to the University of Oxford's Centre for Evidence-Based Medicine. The recommendations were formulated taking into account the quality of evidence on the efficacy, risk and cost of each intervention. ISMAAR recommends adopting a mild approach to ovarian stimulation in all clinical settings as an increasing body of evidence suggests that mild stimulation is as effective as conventional stimulation, while being safer and less expensive. Mild ovarian stimulation could replace conventional stimulation, thus making IVF safer and more accessible worldwide.

Recurrent pregnancy losses, a lasting cause of infertility.

Recurrent pregnancy loss (RPL), defined as two to three spontaneous pregnancy terminations occurring before 12 weeks of gestation, affects approximately 1% of the general population. The causes may include congenital factors that originate with the quality of the gametes (sperm or oocyte) or the resulting embryo, or factors that originate within the uterus. Alterations of endometrial receptivity from endometriosis and/or endometritis, which are associated with impaired action of progesterone, have also been implicated in RPL. Finally, immunologic factors and thrombophilia, congenital and acquired, have also been suspected to cause RPL.

Is there a link between plasma progesterone 1-2 days before frozen embryo transfers (FET) and ART outcomes in frozen blastocyst transfers?

OBJECTIVE: To study the efficacy of combined administration of subcutaneous and vaginal progesterone for priming frozen blastocysts transfers, looking at progesterone levels and ART outcome. DESIGN: Retrospective study. SETTING PATIENTS: Three hundred and twenty frozen blastocyst transfer cycles conducted in 213 women aged up to 42 years, BMI between 18 and 30 kg/m2, with anatomically normal uterus who underwent frozen embryo transfers (FETs) from February 2019 to December 2019 with a combined luteal-phase support (LPS) associating subcutaneous and vaginal progesterone. Patients with recurrent pregnancy loss (RPL) were excluded. RESULTS: When using combined vaginal and subcutaneous LPS, SPL >10.50 ng/mL in 95% of cases, with a minimum value of 7.02 ng/mL. CPR, OPR, and global miscarriage rates were 38.4%, 30.9%, and 19.5%, respectively. Analyzing results per quartiles, revealed that miscarriage rates were significantly inferior, and IR were higher in the upper two quartiles of serum progesterone (>21.95 ng/mL) on the day before FET, while there was no difference in CPR and OPR. CONCLUSIONS: We report ART outcome of frozen blastocyst transfers performed using a combination of vaginal and subcutaneous progesterone for LPS. ART results were honorable and SPL favorable 1-2 days before FET in 99% of cases.

It Is Necessary to Purpose an Add-on to the American Classification of Endometriosis? This Disease Can Be Compared to a Malignant Proliferation While Remaining Benign in Most Cases. EndoGram® Is a New Profile Witness of Its Evolutionary Potential.

Endometriosis is a curious pathology that has been the topic of many international publications. Its etiology remains mysterious but seems to have multiple causes. It is a complex disease whose lesions are very heterogeneous in where they can occur (deep endometriosis, superficial, ovarian cyst), extent, associated symptoms, evolution or aggressiveness of the disease, and response to treatments. Furthermore, it evolves in pushes, remains autonomous, and is responsible for both superficial and deep lesions that explain its two most well know challenges: pain and infertility. It has always been classified by the size of its anatomical lesions-Acosta classification (1), revised by the American fertility society (AFS) (2), and the American society of reproductive medicine (ASRM) classification with a description of the disease at different stages: minimal (score of 1 to 5), mild (3-12), moderate (16 to 40), and severe (>40) (13). If this classification provides a complete repertoire of implants (anatomic) (10), the attribution of points is arbitrary. In fact, the size of the lesions is not synonymous with the difficulty to treat them surgically. Their location, if deep, is larger than the size of ovarian endometriomas. In addition, small anatomical but evaluative lesions will have a larger impact than big fibrous and stable lesions (Figure 1). Thus, attempts to explain their inflammatory side effects have been proposed (14, 15). The French classification nodule, ovaries, adhesions, tube, and inflammation (FOATI) (10) has had the merit of taking this phenomenon into account. In our opinion, we must go much further and propose an amendment in this classification, taking into account the evolution of the lesions and their deep molecular biology because in reality, the lesions are not at the same stage.

Forty years of IVF.

This monograph, written by the pioneers of IVF and reproductive medicine, celebrates the history, achievements, and medical advancements made over the last 40 years in this rapidly growing field.

Development of assisted reproductive medicine in Europe.

The mediocre outcome of microsurgery results in patients with extensive tubal disease was the original driving force behind the search for new methods to assist these infertile patients. Many unsuccessful attempts were carried out before the birth of the first in vitro fertilization baby in Europe 40 years ago. Many pioneers worked tirelessly to develop the tools, procedures, and research necessary. Thanks to the efforts of many, the field of reproductive medicine has grown, advanced, and progressed in ways that seemed nearly impossible just a few decades ago.

[Uterus transplantation: state of knowledge and ethical reflection]. / Greffe utérine : état des lieux et réflexion éthique.

Uterus transplantation: state of knowledge and ethical reflection. Nowadays is uterine transplantation the only treatment for absolute uterine infertility. This experimental surgery is spreading worldwide since the past two years. The first livebirths from uterus transplantations from living donors in Sweden gave the impetus for more research. Since several team works on the uterine transplantation from living or deceased donors. Uterus transplantation and the choice between live and deceased donor raises up technical and ethical questions.

Greffe utérine : état des lieux et réflexion éthique. La greffe utérine est à ce jour le seul traitement de la stérilité d'origine utérine. Cette chirurgie expérimentale est en expansion à travers le monde, en particulier depuis ces deux dernières années. L'élan a été donné par les premières naissances obtenues en Suède en 2014 à l'issue de greffes à partir de donneuses vivantes. Depuis, plusieurs équipes travaillent sur la greffe à partir de donneuses vivantes mais également en état de mort encéphalique. La greffe utérine en tant que telle ainsi que le choix entre les donneuses vivantes et décédées soulèvent de nombreuses questions techniques et éthiques.

Comparative anatomy on 3-D MRI of the urogenital sinus and the periurethral area before and during the second stage of labor during childbirth.

PURPOSE OF THE STUDY: To describe the observable MRI changes in the urogenital sinus during the second stage of labor and delivery by comparing the changes in the positions of the anatomical structures of the maternal perineum using MRI-based vector 3-D models. MATERIALS AND METHODS: Seven pregnant women underwent 3-D MRI sequences using a Philips 1 T Panorama open MRI during the pre-labor period and during the second stage of labor. A 3-D vector reconstruction platform (BABYPROGRESS, France) enabled the transformation of volumes of 2-D images into finite element meshes. The polygonal meshes labeled with the principal components of the urogenital sinus were used as part of a biomechanical study of the pressure exerted on the perineum during fetal descent. RESULTS: The expansion of the urogenital sinus was observed in all patients. Qualitative stretching was observed toward the rear and bottom of the iliococcygeus, pubococcygeus, puborectalis and obturator internus muscles. Significant length differences were measured along the iliococcygeus and pubococcygeus muscles but not along the tendinous arch of the levator ani or the puborectalis muscle. The inversion of the levator ani muscle curvature was accompanied by the transmission of pressure generated during fetal descent to the pubic muscle insertions and the descent of the tendinous arch of the levator ani. CONCLUSION: Mechanical pressures responsible for the tensioning of the constituent muscles of the urogenital sinus were qualitatively identified during the second stage of labor. MRI-based vector 3-D models allow the quantitative assessment of levator ani muscle stretching during labor, but 2-D MRI is not sufficient for describing perineal expansion. Vector 3-D models from larger scale studies have the potential to aid in the calibration of a realistic simulation based on the consideration of the reaction of each muscular element. These models offer perspectives to enhance our knowledge regarding perineal expansion during childbirth as a risk factor for postpartum perineal defects.

Aging and the environment affect gamete and embryo potential: can we intervene?

Optimal maturation of the oocyte depends on its environment and determines embryo competence, because the embryonic genome is not active until the cleavage stage and new mitochondria are not produced until blastulation. Adverse environmental factors include aging, andropause, oxidative stress, obesity, smoking, alcohol, and psychologic stress, whereas androgen supplementation, a prudent diet, exercise, nutritional supplements, and psychologic interventions have beneficial effects. Mitochondrial function and energy production deteriorate with age, adversely affecting ovarian reserve, chromosome segregation, and embryo competence. In aging mice, the mitochondrial cofactor coenzyme Q10 reverses most of these changes. Early human experience has been encouraging, although only a small study using a shorter duration of intervention compared with the murine model has been carried out. Mitochondrial metabolic stress can result in an abnormal compensatory increase in mitochondrial DNA, which can be assessed in biopsied blastomeres of trophectoderm as a predictive biomarker of implantation failure. Psychologic stress may reduce oocyte competence by shifting blood flow away from the ovary as part of the classic "fight or flight" physiologic response, and methods to reduce stress or the body's reaction to stress improve pregnancy success. Enhancing oocyte competence is a key intervention that promises to reduce the number of euploid embryos failing to produce viable deliveries.

Introduction: Male fertility preservation: innovations and questions.

It is now well established that many benign or malignant diseases may by themselves or as result of treatment, impair male fertility. Therefore, preserving the potential of becoming a genetic father represents a major issue. Besides sperm cryopreservation, which is the most reliable method for male fertility preservation, other strategies have more recently emerged, especially in prepubertal boys. Prepubertal germ cell storage from testicular sperm extraction and derivation of male gametes from stem cells may represent a future hope, although raising many ethical issues.

Introduction: Female fertility preservation: innovations and questions.

Oocyte and ovarian tissue cryopreservation represents one of the most important advances in the field of reproductive medicine and biology. Preserving a woman's potential for becoming a genetic mother is now possible for numerous diseases that could impair female fertility either by themselves or as a result of their treatments. However, female fertility preservation is still at the pioneering level and is thus often considered an experimental treatment either from a technical standpoint or in the clinical situation in which it is discussed. As a consequence, many ethics issues are raised with fertility preservation treatment in infants, adolescents, and young women.

Introduction: don't forget the environment of our patients.

The Views and Reviews section of this issue deals with environmental consequences for gametes, embryos, the fetus, newborns, and childhood development.

Quantification of elasticity changes in the myometrium during labor using Supersonic Shear Imaging: a feasibility study.

Very little is known about the myometrium's physiology in terms of its elasticity but shear wave elastography could be an efficient tool to better understand it. This could considerably help the prevention of difficult births, the consequences of which are tremendous for neonate morbidity and pathologies. The purpose of this paper is to show the feasibility of the in vivo monitoring of myometrial stiffness changes in contraction and relaxation during pregnancy. In this study, Supersonic Shear Wave Imaging, a real-time and quantitative imaging technique that has been proven efficient for the investigation of tissue elasticity, was used to quantify the uterus shear-wave speed and stiffness in 6 patients, through the abdomen, using an 8-MHz linear ultrasound probe. Changes in shear wave speed were tracked in real time during the uterine contraction and were well correlated with the uterine pressure, which is currently considered to be a gold standard. These results open a new way to better understand the myometrium contraction during labour.

Mild approaches in assisted reproduction--better for the future?

Mild approaches in assisted reproduction are aimed at achieving quality and not quantity of gametes, embryos, and endometrium with a view to protecting the long-term health and welfare of women and children at an affordable cost. The true success of IVF is in creating children who are full term and normal for gestational age without compromising the health of their mothers. Equal access to IVF treatment can only be achieved by reducing the cost and complications. The state and the society should not suffer as a consequence of IVF treatment. This is the time for change.

Serous adenocarcinoma of the ovary diagnosed during ultrasound evaluation for fertility preservation.

Breast cancer is the most common malignant tumor in women of reproductive age, and fertility preservation counseling is now an integral part of the initial management of these patients. This article reports the case of a 33-year-old woman diagnosed with breast cancer and referred for oncofertility counseling before her treatment. Despite a previous negative cancer workup, a transvaginal ultrasound scan, performed for antral follicle count as part of the initial ovarian reserve assessment, revealed a synchronous ovarian adenocarcinoma. A BRCA1 mutation was confirmed weeks later. This report highlights the role of transvaginal ultrasound in the initial evaluation and reviews the risks associated with fertility preservation in breast cancer patients.