2024-01-17 16:43:12
It is estimated that around 10-15% of pregnancies end prematurely in miscarriage, meaning that one in ten women will experience spontaneous pregnancy loss in their lifetime.
More worryingly, some women face recurrent miscarriages.
This problem affects at least 2 to 3% of couples seeking to conceive a child and is recognized as a major public health issue worldwide. Repeated miscarriages have consequences on physical and mental health, justifying the need for an assessment and coordinated care involving different medical specialties.
What do we know regarding the risk factors associated with recurrent miscarriages? How can we improve their care? Update on the state of knowledge.
The first weeks of life
The birth of a new living human being is the culmination of a complex reproductive process. It begins with fertilization, in other words the fusion of the oocyte and the sperm, which produces a “zygote” (or “fertilized egg”). This single cell then divides into two cells, which will in turn divide, as will their offspring, giving rise to an embryo.
One week following fertilization, this embryo, composed of approximately 200 cells (stage [blastocyste]), migrates from the fallopian tubes to the uterus to implant there. The essential condition for the success of this implantation lies in the adequate preparation of the endometrium, the mucous membrane lining the interior wall of the uterus where the pregnancy takes place, in order to allow implantation of the embryo. This preparation is carefully orchestrated by hormonal fluctuations.
If these optimal conditions are met, the embryo implants and then secretes molecules which stimulate the growth of blood vessels in the endometrium, initiating the formation of the placenta from its own tissues and maternal tissues. Placement of the placenta continues until the start of the second trimester of pregnancy.
This organ plays an essential role in ensuring nutrition, oxygenation and the elimination of metabolic waste from the fetus and in secreting hormones necessary to maintain the pregnancy. Immune cells present in the uterine endometrium, at the interface between maternal tissues and those of the fetus, also participate in implantation, remodeling of the uterine arteries, maternal tolerance towards the fetus as well as defense once morest infections.
Implantation and placentation are therefore determined by a complex set of genetic, anatomical, hormonal, hematological and immunological factors. Disturbances of these elements can [altérer le bon déroulement de la grossesse] and cause a miscarriage.
What do we call “miscarriage”?
Miscarriage is defined as the spontaneous termination of an intrauterine pregnancy before the fetus is considered viable. Due to medical progress, this limit is set before 20 to 24 weeks of pregnancy depending on the country. In France, the threshold that can be considered is 20 weeks of pregnancy, which is equivalent to 22 weeks of amenorrhea (absence of periods).
This may be a termination occurring during a clinically known pregnancy (following a urine or blood test subsequently confirmed by an ultrasound), or during a so-called “biochemical” pregnancy, in other words n having been revealed only by a positive test, without an ultrasound performed (in the case where the pregnancy ended early following implantation).
On the other hand, we do not speak of miscarriage in the case of ectopic pregnancies (also called ectopic pregnancies) or molar pregnancies (a term describing the abnormal growth of cells from a fertilized egg, which does not develop normally in a fetus). Finally, the term miscarriage should be differentiated from implantation failure following the transfer of an embryo obtained by in vitro fertilization.
Isolated miscarriage is a common complication occurring in approximately 10-15% of clinical pregnancies, with the majority occurring during the first trimester. From a medical point of view, these single miscarriages remain benign events, which do not require additional exploration.
It’s a completely different matter if this event happens once more.
What causes repeated miscarriages?
Recurrent miscarriages are considered to affect approximately 2 to 3% of couples trying to conceive. However, the precise estimate of this prevalence remains uncertain. Indeed, there is no consensus on the definition, and may differ depending on international scholarly societies. Furthermore, miscarriages of non-visualized pregnancies are not always taken into account.
According to recent recommendations from theEuropean Society of Human Reproduction and Embryology (European scientific organization founded in 1985, dedicated to promoting research, education and care in the field of human reproduction and embryology), the diagnosis of recurrent spontaneous miscarriages – in English recurrent pregnancy loss – must be retained from the occurrence of two or more miscarriages, whether or not they are consecutive. This definition includes biochemical pregnancies and applies even if a live birth occurred between two pregnancy losses.
Multiple factors and causes have been identified as being associated with risk of occurrence and recurrence of miscarriage, with varying degrees of scientific evidence.
Among these factors, two main ones are known to increase the risk of recurrent miscarriages: the number of previous pregnancy losses a woman has and advanced maternal age.
A study in the Danish population estimated that the risk of further pregnancy loss was approximately 30% following two miscarriages and more than 40% following three or more miscarriages.
The increased risk of miscarriage with advanced maternal age is due in part to deterioration in oocyte quality, with a progressive accumulation of genetic mutations over time. This increases the risk of embryos having chromosome number abnormalities, also called “aneuploidies,” often making them unviable.
Although chromosomal abnormalities are one of the main causes of repeated miscarriages, there is a significant decrease in the proportion of aneuploid embryos aborted as the number of previous miscarriages increases. They thus go from 60% among women who have already suffered two or three miscarriages to 25% among those who have experienced six or more previous miscarriages, suggesting that other mechanisms are attributable to these repeated pregnancy losses.
Lifestyle habits can have a negative influence on reproductive health and increase the risk of miscarriages, in particular the consumption of tobacco and alcohol, the intake of excess caffeine (beyond 300 mg per day), or even night work. Likewise, maternal obesity is associated with an increased risk of pregnancy loss, due to an alteration in the receptivity of the endometrium or an association with other pathologies, particularly endocrine.
Aging and poor lifestyle (unbalanced diet, excessive alcohol consumption, smoking, lack of exercise, etc.) in the male partner can also alter the quality of sperm genetic material and increase the risk of aneuploidy in the embryo. .
Repeat miscarriages can also be attributed to a variety of gynecologic causes, including uterine malformations, adhesions in the uterine cavity, endometriosis, or chronic endometritis (infection of the endometrium).
Endocrine pathologies, such as unbalanced diabetes and thyroid disorders, but also blood clotting disorders affecting the circulation necessary for implantation and development of the placenta, or dysfunctions of the immune system altering tolerance towards the embryo, can also be involved in these recurrent losses.
A major public health problem
Recurrent miscarriages represent a major public health issue worldwide.
From a psychological point of view, these repeated losses have a significant impact on the emotional well-being and stability of the couple, with a high risk of depression and anxiety for each partner.
In addition, the recurrence of these miscarriages may be indicative of the harmful influence of behavioral or environmental factors on overall health or of undiagnosed pathologies.
The occurrence of repeated miscarriages is thus associated with an increased risk of obstetric complications in the event of subsequent active pregnancies, in particular premature delivery, and of long-term complications in patients, in particular cardiovascular problems.
The need for appropriate support
A significant part of the distress experienced by couples facing repeated miscarriages lies in the confusion and wandering of care.
Often, having suffered “only” two or three miscarriages is downplayed and considered a “normal” reality. In addition, centers offering consultations specifically dedicated to the evaluation of recurrent miscarriages are still rare.
However, as soon as two previous miscarriages occur, it is recommended to refer the couple to a gynecologist for a specialized assessment. This evaluation begins with an in-depth interview, including the complete obstetric history, medical history, family history and lifestyle habits of both partners.
The prescribed assessment will include at least a pelvic ultrasound, if necessary supplemented by a hysteroscopy, as well as a blood test to assess thyroid function and look for the presence of specific autoantibodies (“antiphospholipid antibodies”) which can cause problems. coagulation. Depending on the situation, other investigations may be considered, such as a chromosomal analysis of the couple or an evaluation of sperm parameters.
In addition, this consultation offers the possibility of advising the couple if necessary on improving their lifestyle, as well as offering psychological support. Collaboration with other specialists, such as an endocrinologist, an internist, or a physician specializing in reproductive medicine, may be necessary to ensure a comprehensive and personalized approach.
No preimplantation diagnosis in France
Preimplantation diagnosis (PGD) is a reproductive biology technique which makes it possible to genetically analyze embryos obtained by in vitro fertilization before considering their transfer, in order to detect possible embryonic chromosomal anomalies.
PGD is practiced in some countries, such as Spain, for women suffering from repeated miscarriages, allowing the selection of euploid embryos. This approach seems particularly beneficial for women of advanced age.
However, in France, this technique is not legally authorized in the context of miscarriages, due to ethical considerations. Its use remains reserved for specific medical situations, in particular to prevent the transmission of serious and hereditary genetic diseases.
Towards new therapies
The chances of having a healthy baby remain favorable for couples, but as we have seen, the success of a pregnancy is influenced by invariable factors such as the age of the mother and the number of previous miscarriages. .
Some couples may experience a significant number of miscarriages even though all currently recommended tests show normal results. Furthermore, even if an anomaly is detected during the assessment, the treatment of this cause does not always guarantee its effectiveness, which underlines the complexity and multifactorial nature of miscarriages.
However, research is increasingly interested in this problem, in order to better understand its mechanisms. New therapeutic avenues are emerging from this work. This is, for example, the case for immunomodulatory therapies. Developed following the identification of local immune imbalances in the endometrium of patients suffering from repeated unexplained miscarriages, they are currently the subject of in-depth studies.
In Japan, a therapeutic trial recently demonstrated that immunoglobulin infusions administered at the start of a new pregnancy significantly increased the rate of live births in women who had experienced at least four unexplained pregnancy losses, including at least one with proof loss of a euploid embryo.
Hopeful results for couples facing repeated unexplained miscarriages…
To know more :
Every year, the French International Congress on Repeated Terminated Pregnancies is organized in France. Open to all health professionals upon registration, its objective is to recall recent recommendations from learned societies, to share the results of recent publications and to present current research protocols.
1705512872
#update #treatment
