Ivo A Brosens

• MD PhD FRCOG a.e.
• Professor Emeritus at KU Leuven

This authoritative textbook provides a much-needed guide for postgraduate trainees preparing for the European Board and College of Obstetrics and Gynaecology (EBCOG) Fellowship examination. Published in association with EBCOG, it fully addresses the competencies defined by the EBCOG curriculum and builds the clinical practice related to these compe...

This authoritative textbook provides a much-needed guide for postgraduate trainees preparing for the European Board and College of Obstetrics and Gynaecology (EBCOG) Fellowship examination. Published in association with EBCOG, it fully addresses the competencies defined by the EBCOG curriculum and builds the clinical practice related to these compe...

Objective: Based on the hypothesis that neonatal uterine bleedings (NUB), occurring mostly in the first week after birth, could represent a pathogenetic mechanism for early-onset endometriosis, this systematic review (SR) was undertaken to evaluate the prevalence and screening strategies used to assess and quantify NUB. Design: Both a SR and a s...

Neonatal uterine bleeding occurs in the 3rd–7th day postpartum. Little attention is paid to it. Data are available in the German, French, and Serbian literature. The reported incidence of visible vaginal bleeding occurs in 3.3–5.3% of the female neonates, while the incidence of occult bleeding by testing Hgb was 25.4–61.3%. The incidence of 0.78% i...

There is emerging evidence that early uterine development in humans is an important determinant of conditions such as ontogenetic progesterone resistance, menstrual preconditioning, defective deep placentation and pre-eclampsia in young adolescents. A key observation is the relative infrequency of neonatal uterine bleeding and hormone withdrawal at...

Introduction: The contraceptive activity of synthetic progestins is mediated through three basic mechanisms: (a) An anti-gonadotrophic action leading to the inhibition of ovulation; (b) Changes in cervical mucus characteristics that inhibit sperm penetration and (c) desynchronization of the endometrial picture necessary for implantation. Areas co...

Based on a variety of tissue samples, including Caesarean hysterectomy specimens with the placenta in situ, a detailed map of uteroplacental vascular lesions was established in over a century of research. One such lesion is acute atherosis of unremodelled basal and uteroplacental arteries, defined by the presence of fibrinoid necrosis, subendotheli...

Introduction: Steroid hormones are responsible for specific changes in the endometrium during the menstrual cycle, when they are sequentially secreted and, because of this, in the early days sequential combined oral contraceptive regimens were utilized. The same basic concept has been utilized with multi-phasic regimens, in order to produce endomet...

Research on the placenta as the interface between the mother and the fetus has been undertaken for some 150 years and in two subsequent reviews, we attempted to summarize the situation. In the first part, we described the discovery of unique physiological modifications of uteroplacental spiral arteries enabling them to cope with a major increase in...

The term placental bed was coined to describe the maternal-fetal interface (ie, the area in which the placenta attaches itself to the uterus). Appropriate vascularization of this area is of vital importance for the development of the fetus; this is why systematic investigations of this area have now been carried out. Initially, the challenge was th...

Autoimmune diseases (AIDs) affect women and men with a 2:1 ratio, which suggests that hormonal contraceptives play a role in their clinical course. Combined oral contraceptives have complex, sometimes contradictory, effects on AIDs; they can worsen the situation in women with systemic lupus erythematosus and with anti-phospholipid syndrome, conditi...

Background: We reviewed published cases of uterus-like mass (U-LM), endomyometriosis, polypoid adenomyoma (PA), adenomyomatous polyp, atypical PA (APA), and adenomyoma. Search methods: PubMed, Medline, and Scopus searches of all cases published in the databases till November 26, 2018. Results: We identified 45 case reports of U-LM in the pelvi...

Autoimmune diseases (AIDs)are a heterogeneous group of disorders in terms of clinical manifestations, pathogenesis, and prevalence, and there is no agreement to date on a common classification. Adaptive immune responses are responsible for the existence of AIDs, although innate immunity is also involved in misguiding the immune response against sel...

We explore the potential role of the endothelial lining of uteroplacental arteries in the pathogenesis of preeclampsia, a severe pregnancy disorder characterized by incomplete invasion of the uterine vasculature by extravillous trophoblast and angiogenic imbalance. In normal pregnancy, the endothelium disappears progressively from the uteroplacenta...

Uterine fibroids are the most common gynecological disorder, classically requiring surgery when symptomatic. Although attempts at finding a nonsurgical cure date back to centuries, it is only around the middle of the last century that serious attempts at a medical treatment were carried out. Initially, both progestins and estrogen–progestin combina...

Introduction: Following a historical overview, the ovulation-inhibiting effect of various orally-administered estrogen-progestin combinations (COCs) are examined for their components alone or in the various combined formulations. Special emphasis is given to products containing natural estrogens. Areas covered: Inhibition of ovulation with progesti...

Preeclampsia is an important cause of maternal and perinatal morbidity, especially in first-time pregnant adolescent women. Although prevention of preeclampsia has been attempted for many decades, effective intervention can only be achieved upon the full elucidation of the risk factors and mechanisms of disease. As the pathogenesis of preeclampsia...

After some 60 years of ever-increasing utilization, hormonal contraception (HC) has made a major impact in the lives of women worldwide. This chapter discusses the different meaning that family planning has taken today in industrialized and in developing countries, the reason being that in the former fertility is almost always at, or below, replace...

Neonatal uterine bleeding (NUB), or neonatal menstruation is today a totally neglected phenomenon, labelled as “perfectly normal and therefore not worth investigating”. Yet, over the last two centuries, its frequency, characteristics and pathophysiology have been carefully investigated, leading to the conclusion that its occurrence is a strong mark...

The occurrence of a „spontaneous hemoperitoneum in pregnancy” (ShiP) is a rare, little-known but potentially fatal complication for both mother and fetus, a real emergency that often and in many ways mimics the clinical picture of a placental abruption or uterine rupture. Usually, the diagnosis is made only at the time of an urgent exploratory lapa...

Aim: The present paper intends in the first place to clarify the confusing terminology for describing the vascular pathology of the placental bed in relation to long-term risk of cardiovascular disease. Methods: Systematic review of relevant topics. Results: The maternal blood supply to the placenta is achieved by some 100 utero-placental spir...

Spontaneous Hemoperitoneum in Pregnancy (SHiP), an unprovoked (nontraumatic) intraperitoneal bleeding in pregnancy (up to 42 days postpartum), is associated with serious adverse pregnancy outcomes. To evaluate the clinical consequences of SHiP and its association with endometriosis, a systematic review was conducted according to the PRISMA guidelin...

Increasing evidence indicates that early onset endometriosis (EOE), starting around menarche or early adolescence, may have an origin different from the adult variant, originating from neonatal uterine bleeding (NUB). This implies seeding of naïve endometrial progenitor cells into the pelvic cavity with NUB; these can then activate around thelarche...

The pathophysiology of (deep) endometriosis is still unclear. As originally suggested by Cullen, change the definition "deeper than 5 mm" to "adenomyosis externa." With the discovery of the old European literature on uterine bleeding in 5%-10% of the neonates and histologic evidence that the bleeding represents decidual shedding, it is postulated/h...

Introduction: The pharmacodynamic effects of various combined oral estrogen-progestin combinations (COC) are examined for their components alone or in the various combined formulations. Special emphasis is given to products containing natural estrogens. Areas covered: Recent information on the effect of androgens, estrogens, progestins, as well as...

Pregnant nulliparous adolescents are at increased risk - inversely proportional to their age - of major obstetric syndromes, including preeclampsia, fetal growth restriction and preterm birth. Emerging evidence indicates that biological immaturity of the uterus accounts for the increased incidence of obstetrical disorders in very young mothers, pos...

Background: Spontaneous hemoperitoneum in pregnancy (SHiP) is a rare, life-threatening event, particularly relevant to women with endometriosis or deciduosis. Methods: To determine the type of lesions leading to SHiP, a literature search was conducted among all published SHiP cases. From a total of 1,339 publications, information on pathological...

We present a review of available diagnostic tools for adolescent endometriosis, a condition that may have a different pathogenesis than the adult form and therefore necessitates specific methodologies. The new theory provides that endometrial stem/progenitor cells in neonatal uterine bleeding may be causally linked to early-onset endometriosis, the...

There continues to be debate over the nature and progression of ovarian endometriomas in adolescence due to the possibility that they may have a different origin and to the impossibility to be able to predict progress. The hypothesis of a different origin traces its roots in the phenomenon called “neonatal menstruation” (NUB), occurring in approxim...

Neonatal uterine bleeding (NUB) has been carefully studied in the past through case reports, small series, clinical cohort studies, pathology investigations of fetal and neonatal. Following a historical recount, this review summarizes biological mechanisms conditioning NUB, starting from the persistence till birth of an 'ontogenetic progesterone re...

Introduction: The risk-benefit profile of any pharmacologic agent must be evaluated against risks connected with the events to be avoided. This is especially true in the case of hormonal contraception, not intended to combat a disease. Over the six decades during which their use has progressively expanded, the risk-benefit profile of combined oral...

A fortuitous collaboration between British and Belgian researchers more than 50 years ago led to discovery that major obstetrical disorders, such as preeclampsia and fetal growth restriction, originate from vascular lesions in placental bed, i.e. the myometrial portion of the uterine spiral arteries. William B Robertson, a gregarious pioneering vas...

Objective: To report pregnancy outcomes of SHiP (spontaneous haemoperitoneum in pregnancy) and the association with endometriosis. Design: Retrospective case note review. Setting: Dutch referral hospitals for endometriosis. Sample: Eleven women presenting with 15 events of SHiP. Methods: In collaboration with the Dutch Working Group on End...

If and how endometriosis impact on obstetric outcome are two questions that have generated considerable debate in recent years—with limited cohort and large population studies often arriving at different answers. A new population-based study from Glavind and colleagues (1) seems to settle the “if” question. Analysis of 82,793 singleton pregnancies...

Introduction: Treatment of ovarian endometriomas is commonly achieved through laparoscopic surgery and this can be effective in eliminating the disease, although a majority of recent trials documented an adverse effect of surgery on ovarian reserve markers. With the advancement in imaging techniques, ovarian endometriomas are increasingly diagnosed...

Neonatal uterine bleeding (NUB) occurs in approximately 5% of newborns and is generally considered to be of little clinical significance. However, the real clinical importance of this condition and its long-term implications remain to be determined. The reason why NUB is rare despite high circulating levels of progesterone can be attributed to a pr...

Objective: To evaluate existing evidence of a possible association in women with endometriosis between controlled ovarian hyperstimulation plus embryo transfer (COH-ET) and the occurrence of spontaneous hemoperitoneum in pregnancy (SHiP). Design: Comprehensive review. Setting: Not applicable. Patient(s): None. Intervention(s): An electroni...

As of today, there is no proof that the ovarian endometrioma in an adolescent represents a progressive condition, although evidence is accumulating that active management of this phenotype of endometriosis is warranted. Indeed, although symptoms will often start at a young age, even before menarche, a major delay between their onset and final diagn...

Accumulating evidence indicates that adolescent endometriosis is common and often severe. Here we explore the possibility that seeding of naive endometrial progenitor cells into the pelvic cavity early in life, that is, at the time of neonatal uterine bleeding or soon after the menarche, results in more florid and progressive disease, characterized...

Management of ovarian endometrioma is a matter of debate between those advocating early treatment and those believing that cysts less than 3 cm in diameter should not be submitted to surgery. To explore a new approach to its management capable of preserving future fertility, the molecular pathology of ovarian endometrioma is reviewed and mechanisms...

Today, a new category of fertility-regulating agents has been created: long-acting, reversible hormonal contraceptives; they minimize compliance, while maximize effectiveness. They comprise subdermal implants and intrauterine devices. Other long-acting agents exist, such as Depo Provera and Noristerat. Use of Depo Provera and Noristerat carries gre...

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Our understanding of adenomyosis remains hampered because of the lack of clarity of the clinical significance of the finding of aberrant endometrial glands and stoma within the myometrium. Despite the growing number of publications and the renewed interest generated by advances in vaginal ultrasounds and magnetic resonance imaging as non-invasive d...

There are many case reports of the rare cystic uterine lesions which are often classed as variants of adenomyosis. The introduction of Ultrasound and Magnetic Resonance Imaging has enabled non-invasive diagnosis. Cystic variant of adenomyosis, which is often amenable to surgical treatment, should be suspected in cases of refractory dysmenorrhoea. M...

Past studies have clearly shown the existence of a spectrum of endometrial progesterone responses in neonatal endometrium, varying from proliferation to full decidualization with menstrual-like shedding. The bleedings represent, similar to what occurs in adult menstruation, a progesterone withdrawal bleeding. Today, the bleeding is completely negle...

The presence of multiple ovarian cysts, anovulation, and endometrial progesterone resistance in the neonate seems remarkably similar to ovarian and endometrial features of the polycystic ovary syndrome (PCOS) of adolescent and adult women. In fact, in the absence of cyclic menstruations after menarche, the neonatal progesterone resistance is likely...

Scientific data on the phenomenon of uterine bleeding in the neonate (NUB) began to appear over a century ago when angiogenesis and petechial haemorrhages in the endometrium of newborn female infants, as well as fluid blood within the uterine cavity, were first described. A thorough search of the 20th century literature was carried out to identify...

Reviewing the life cycle of endometriosis the hypothesis is formulated that neonatal uterine bleeding may be a cause of early onset endometriosis as well as major obstetrical disorders including pre-eclampsia and fetal growth restriction. With regard to endometriosis, a visible vaginal uterine bleeding occurs in 5% of the neonates: this vaginal ble...

The influence of intrauterine environment on the risk of endometriosis is still controversial. Whether birth weight modifies the risk of endometriosis in adulthood remains an open question. For this purpose, we designed a case-control study involving 743 women operated on for benign gynecological indications from January 2004 to December 2011. Stud...

The incidence and severity of endometriosis in adolescent are comparable with the incidence in adult women. The mean delay between the onset of symptoms and the final diagnosis varies between 6.4 and 11.7 years. The longer the diagnosis is delayed, the more the endometriosis can progress to a more severe stage certainly in the group of patients wit...

The fetus is exposed to high plasma concentrations of unbound estrogens and progesterone throughout pregnancy. However, secretory or decidual changes in the fetal uterus occur relatively infrequently before birth, suggesting a variable endometrial progesterone response at the time of birth. Arguably, partial progesterone resistance that persists in...

The first description of a condition today recognised to be a form of adenomyosis was published in 1860 by Carl Rokitansky who reported one case of fibrous polyps of the uterus, containing nests of endometrial cells. In 1882 von Recklinghausen suggested the name adenomyoma uteri and by the end of the nineteenth century the condition was clearly des...

The aim of this study is to verify that 10 % of N2O in CO2 sufficiently reduces pain to permit laparoscopy under local anesthesia. In nine patients undergoing laparoscopy under local anesthesia for tubal sterilization, a mixture of 86 % of CO2, 10 % of N2O, and 4 % of oxygen (the Gas Mixture) was used for the pneumoperitoneum. For CO2, N2O, and for...

The life-cycle approach to endometriosis highlighted unexpected features of the condition; the same approach was therefore applied to gain insight into the clinical features of adenomyosis and to draw a comparison with endometriosis. This is possible today thanks to new imaging techniques enabling non-invasive diagnosis of adenomyosis. The specific...

Complex pathologies associated with chronic health conditions must be dealt in a coordinated way and the ‘multidisciplinary team’ approach (MDTA) represents the most efficacious way of managing these patients. Over the last 25 years, the initial limited field for joint interventions by several specialists has been progressively expanded and this ar...

In 1908, Cullen described the first cases of cystic adenomyosis in his textbook on adenomyomata. Although not very common, with the introduction of noninvasive imaging techniques such as magnetic resonance imaging (MRI) and 3-D transvaginal ultrasound, an increasing number of cases have been reported. Patients primarily complain of severe dysmenorr...

An association between endometriosis and infertility has been confirmed by a large number of studies, although mechanisms are still debated. The availability of in vitro fertilization represented a major step forward in achieving pregnancy in women with endometriosis, although in both peritoneal and ovarian disease, there is an adverse effect on ov...

A dispute has recently emerged whether early descriptions exist of the condition we name endometriosis. A first question is: 'Who identified endometriosis?' To respond, two non-complementary methods have been employed: searching for ancient descriptions of symptoms associated with endometriosis or, alternatively, identifying researchers who describ...

Purpose of review: We adopted a life-cycle approach to further our understanding of the natural history of the cystic forms of uterine adenomyosis first described by Cullen in 1908. Search Strategy Scopus and PubMed were searched for all terms referring to cystic variant of adenomyosis or adenomyoma. References found in major publications were als...

Introduction: Several selective progesterone receptor modulators (SPRMs) show promise in several areas of medicine and this work has been summarized by us in 2008. Areas covered: Since the publication of our reviews, several developments have taken place in the field of reproductive medicine. The first is emergency contraception (EC). Two SPRMs...

The pathogenesis of early-onset endometriosis has recently been revisited, sparked by the discovery of endometrial stem/progenitor cells and their possible role in endometriosis, and because maternal pregnancy hormone withdrawal following delivery induces uterine bleeding in the neonate. The neonatal uterus has a large cervix to corpus ratio which...

The incidence of endometriosis in the infertile female is estimated to be between 20 and 50 %. Although the causal relationship between endometriosis and infertility has not been proven, it is generally accepted that the disease impairs reproductive outcome. Indirect imaging techniques and transvaginal laparoscopy now offer the possibility of an ea...

The presence of endometriosis, from minimal/mild disease up to the rASRM („revised American Society for Reproductive Medicine classification for endometriosis”) stages III and IV, has been described repeatedly in adolescent women. The complaints are common and elicit compassion, but rarely stimulate a thorough research of the cause. The clinical re...

BACKGROUND Adenomyosis and endometriosis were initially described as ‘adenomyoma’. When the retrograde menstruation theory became widely accepted to explain the pathogenesis of endometriosis, since it does not explain adenomyosis, the two conditions came to be seen as distinct entities. However, emerging evidence suggests that both diseases may be...

Present management of the ovarian endometrioma focuses on the size of the cyst and dictates that surgery should not be performed unless this exceeds 3 cm, which neglects the complex pathology of this condition. Studies of ovaries with the endometrioma in situ show progressive smooth muscle cell metaplasia and fibrosis of the cortical layer as the m...

We elaborate on a new theory to explain pelvic endometriosis, including endometriosis in premenarcheal girls, based on the finding that the neonatal endometrium can display secretory activity immediately after birth and, in some cases, changes analogous to those seen at menstruation in adults. The neonatal uterus is therefore capable of shedding it...

Transplanting a uterus has unique characteristics, since a successful outcome is represented only by the birth of a viable healthy child. For this reason, critical issues in this type of transplantation differ profoundly from those of other solid organs and, beside a functioning uterus, involve 3 additional steps. First, at the time of implantation...

Pregnancy following a solid organ transplantation is becoming relatively common, particularly after kidney and liver transplantations. In both groups however, major obstetrical syndromes are more frequent than in the general population. Obstetrical syndromes, including pre-eclampsia, preterm birth and fetal growth restriction, are higher for kidney...

Abstract Adverse living and nutritional conditions in utero and in early infancy may influence the risk of diseases in adult life, because fetal growth seems determined by interactions between the environment and the fetal genome and these interactions may determine the risk of postnatal disease and the capacity to react to and cope with the postna...

Endometriosis in the adolescent has, in recent years, been discovered to be a challenging problem in gynaecology. Although the pain may start at a young age, even before the onset of menstruation, the diagnosis by laparoscopy is almost always postponed for several years, by which time destructive lesions have affected the tubo-ovarian structures an...

Study question To determine whether hypoxic microenvironment might be a factor in influencing cell migration of endometrial stromal cells in endometriosis

Abstract Recently, two authors suggested that killing a healthy newborn might be morally permissible, subsuming it under the heading of 'after birth abortion'. Their proposed new definition implies that infanticide should be permitted whenever II trimester abortion for social reasons is. The suggestion stirred public outcry; nonetheless it needs to...

To improve the still fragmented understanding of endometriosis a life-cycle approach is adopted that revealed unexpected aspects of the natural history of the disease throughout a woman's life. Three age related stages of endometriosis are distinguished. In premenarcheal and adolescent endometriosis two types can be distinguished: a "classic form",...

Pregnancy after kidney and liver transplantation is becoming relatively common, although, in both groups, maternal complications are higher than in the general population. Both mean gestational age and mean birthweight seems significantly greater for liver transplant versus kidney transplant recipients and the risk of hypertension during pregnancy...

There are now convincing data showing that cystectomy of the endometrioma is not only no cure of infertility, but may harm follicle reserve. The question arises why is cystectomy for an endometrioma, in contrast with other benign cysts, a risk for follicle reserve and how can ovarian damage be prevented. Surgical specimens of ovaries with endometri...

As discussed in the current issue of this journal, uterine transplant- ation in the human is becoming a real possibility, and a range of re- search and ethical criteria have been proposed to regulate its introduction (Del Priore et al., 2012). However, the need to ensure a normal pregnancy outcome will become a major clinical challenge for several...

The diagnosis of adenomyosis using noninvasive techniques such as vaginal ultrasounds and magnetic resonance has clear clinical applications and has renewed the interest in the pathogenesis of uterine adenomyosis. However, the research remains hampered by the lack of consensus on the classification of lesions. Magnetic resonance imaging and transva...