Spontaneous haemoperitoneum in pregnancy and endometriosis: a case series.

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 METHODS: In collaboration with the Dutch Working Group on Endometriosis, unpublished cases of SHiP that occurred in the Netherlands between 2010 and 2015 were retrieved. MAIN OUTCOME MEASURES: Maternal and perinatal mortality and morbidity. RESULTS: SHiP occurred predominantly in the second and third trimester of pregnancy. The earliest and major presenting symptom was an acute onset of abdominal pain, often combined with low haemoglobin levels or signs of fetal distress. Imaging was a diagnostic tool when free peritoneal fluid could be observed. For surgical treatment of the bleeding site, a midline laparotomy was mostly needed, the median estimated amount of blood loss was 2000 mL. No fetomaternal or perinatal mortality was reported, despite a high rate of preterm births (54.5%). In all women, endometriosis was diagnosed at a certain moment in time and therefore was probably involved in the pathogenesis of SHiP. Four women showed recurrence of SHiP. In one of these cases the second event of SHiP occurred in a subsequent pregnancy. CONCLUSION: Pregnancy outcomes of SHiP are improving when compared with previous reports, with absent fetomaternal and perinatal mortality in this recent series. Growing knowledge and adequate multidisciplinary intervention may have contributed to these favourable results. Increasing awareness of this serious complication of pregnancy is advocated, especially in women diagnosed with endometriosis. TWEETABLE ABSTRACT: Growing awareness of SHiP is advocated, especially in women diagnosed with endometriosis.

The perinatal origins of major reproductive disorders in the adolescent: Research avenues.

The fetal endometrium becomes responsive to steroid hormones around the fourth month of pregnancy starting with an oestrogenic phase, which is followed late in pregnancy by a secretory phase. Based on post-mortem studies, the endometrium at birth is secretory in only one-third of neonates and proliferative in the remaining cases. Decidual or menstrual changes are rare in fetal endometrium despite high circulating steroid hormone levels, which drop rapidly after birth. Hence, acquisition of progesterone responsiveness appears to be dependent on endometrial maturation and relative immaturity may persist in a majority of girls until the menarche and early adolescence. Two major reproductive disorders have been linked with either advanced or delayed endometrial maturation. First, early-onset endometriosis may be caused by menstruation-like bleeding in the neonate, leading to tubal reflux and ectopic implantation of endometrial stem/progenitor cells. Second, persistence of partial progesterone resistance in adolescent girls may compromise deep placentation and account for the increased risk of major obstetrical syndromes, including preeclampsia, fetal growth retardation and preterm birth. The concept of neonatal origins of common reproductive disorders poses important research challenges but also subsumes potential new preventative strategies.

Hysteroscopic diagnosis and excision of myometrial cystic adenomyosis.

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 dysmenorrhea, chronic pelvic pain, and dysfunctional uterine bleeding. Currently, it is unclear whether adenomyosis and, more specifically, cystic adenomyosis can be an underlying reason for impaired fertility and reproductive outcome. With the postponement of childbearing, the number of patients with adenomyosis and cystic adenomyosis seeking fertility treatment is increasing. Therefore, in these patients, uterine exploration should include not only the evaluation of the endometrial cavity but also the exploration of the sub-endometrial zone. Indirect imaging techniques, combined with office mini-hysteroscopy, offer the possibility of complete uterine exploration. Two patients with cystic adenomyosis are described in this paper: one had the chief complaint of menorrhagia and the other was referred for evaluation of infertility and severe dysmenorrhea. The aim of these case reports is to present hysteroscopic dissection and ablation of adenomyotic cysts as an alternative procedure for the surgical management of this condition.

Transvaginal endoscopy and small ovarian endometriomas: unravelling the missing link?

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 early stage diagnosis. Although it remains debated whether the disease is progressive, treatment in an early stage is recommendable as it carries less risk for ovarian damage, hence premature ovarian failure. Under water, inspection with the technique of transvaginal hydrolaparoscopy (THL) accurately shows the invagination of the ovarian cortex as minimal superficial lesions but with the presence of well-differentiated endometrial like tissue at the base, the lateral walls and especially the inner edges of the small endometrioma. An inflammatory environment is responsible for the formation of connecting adhesions with the broad ligament and lateral wall with invasion of endometrial-like tissue and formation of adenomyotic lesions. In around 50 % of the small endometriomas, adhesiolysis is necessary at the site of invagination with opening of the cyst, to free the chocolate content and hereby recognize the underlying endometrioma. The detailed inspection of these early-stage endometriotic lesions at THL reunites the hypothesis of Sampson with the observation of Hughesdon.

Potential role of endometrial stem/progenitor cells in the pathogenesis of early-onset endometriosis.

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 is functionally blocked with mucous, supporting the concept of retrograde shedding of neonatal endometrium. Only 5% show overt bleeding. Furthermore, the presence of endometriosis in pre-menarcheal girls and even in severe stage in adolescents supports the theory that early-onset endometriosis may originate from retrograde uterine bleeding soon after birth. Endometrial stem/progenitor cells have been identified in menstrual blood suggesting that they may also be shed during neonatal uterine bleeding. Thus, we hypothesized that stem/progenitor cells present in shedding endometrium may have a role in the pathogenesis of early-onset endometriosis through retrograde neonatal uterine bleeding. During the neonatal and pre-pubertal period, shed endometrial stem/progenitor cells are postulated to survive in the pelvic cavity in the absence of circulating estrogens supported by niche cells also shed during neonatal uterine bleeding. According to this hypothesis, during thelarche, under the influence of rising estrogen levels, endometrial stem/progenitor cells proliferate and establish ectopic endometrial lesions characteristic of endometriosis. This New Research Horizon review builds on recent discussions on the pathogenesis of early-onset endometriosis and raises new avenues for research into this costly condition.

Endometriosis in adolescents is a hidden, progressive and severe disease that deserves attention, not just compassion.

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 and severely compromised fecundability. Several factors may play a role, but one important reason for this disease progression is likely to be the delay in diagnosis. Therefore, transvaginal ultrasounds and transvaginal access with a less invasive needle endoscopy are recommended for exploration of the pelvis, diagnosis of endometriosis and treatment at an early stage before severe lesions develop.

Defective myometrial spiral artery remodelling as a cause of major obstetrical syndromes in endometriosis and adenomyosis.

Endometriosis and adenomyosis are characterized by the presence of ectopic endometrium, but are also associated with functional and structural changes in the eutopic endometrium and inner myometrium. Alterations in the inner myometrium occurring in women with endometriosis and adenomyosis may be at the root of a defective remodelling of the myometrial spiral arteries from the onset of decidualization and result in vascular resistance and increased risk of defective deep placentation. The association of major obstetrical syndromes and different types of defective remodelling of the myometrial spiral arteries has been well documented. The possibility of a link between both endometriosis and adenomyosis and some major obstetric syndromes remains controversial because of at least two factors: first, changes of the inner myometrium are frequently present in women with endometriosis but the diagnosis requires high-resolution imaging such as magnetic resonance which is not routinely performed and second, patients with endometriosis are frequently subjected to prolonged hormone suppressive therapy. Indeed, there is evidence that pre-treatment with a Gonadotropin Releasing-Hormone analogue can improve the uterine microenvironment and implantation rate following IVF in infertile patients with endometriosis.

Early stage management of ovarian endometrioma to prevent infertility.

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 endometrioma in situ show in the majority of cases manifestly a combined -extra-ovarian and intra-ovarian pathology with the cortex invaginated to form a pseudocyst. The extra-ovarian pathology includes endometrial lining of the cortex, bleeding and adhesions with surrounding tissues. The intra-ovarian pathology is characterized by microscopic stromal implants, fibrosis, smooth muscle metaplasia and -arteriosclerosis, all affecting follicle reserve in the endometrioma bed. Clinically, ovarioscopy allows differential diagnosis (e.g. luteal cyst) and evaluation of the degree of fibrosis and darkening of the cortical wall. Transvaginal colour Doppler sonography can demonstrate the presence and extent of devascularisation in the endometrioma bed. Given this reality, surgery should be based on evaluation of the pathology of the endometrioma bed, but not on the mere size of the chocolate cyst. The main clinical problem is indeed the delayed diagnosis and consequently advanced irreversible cortical damage. Therefore, the sooner endometriomas are diagnosed, the better, because it increases the chances that vascularisation of the endometrioma bed is preserved. Finally, ablation, but not excision is the treatment of choice. The diagnosis of endometriosis is traditionally based on laparoscopy, but in a sexually active adolescent transvaginal endoscopy can be proposed.

Rationale of first-line endoscopy-based fertility exploration using transvaginal hydrolaparoscopy and minihysteroscopy.

The transvaginal access for exploration of tubo-ovarian function in women with unexplained infertility has been revived since transvaginal hydrolaparoscopy (THL) was introduced in 1998. One prospective double-blind trial and several reviews have validated the diagnostic value of THL in comparison with laparoscopy for the exploration of women with unexplained infertility. A review of the recent literature confirms the efficacy and safety of the technique for first-line endoscopy-based exploration of fertility. The standard policy of 1-year delay for laparoscopic investigation in unexplained infertility is challenged. In older women and particularly in women experienced in fertility awareness methods, THL and minihysteroscopy can be performed after a waiting period of 6-12 months.

Deep placentation.

Deep placentation in human pregnancy is realised by deep invasion of the placental bed by the extravillous trophoblast, involving the decidua and the inner (junctional zone) myometrium. Interstitial invasion of the stroma and endovascular trophoblast invasion of the spiral arteries both occur. Deep endovascular trophoblast invasion into the myometrial segments of spiral arteries is important for proper placental functioning. Before this extended vascular invasion begins, decidua-associated vascular remodelling, which includes swelling and disorganisation of the vascular smooth muscle, occurs during a period of rising placental oxygen. This early remodelling step may accommodate the progressively increasing maternal blood flow to the developing placenta. The subsequent trophoblast-associated remodelling step enhances and stabilises the widening of the vessels, whereas the vascular smooth muscle and elastic lamina are replaced by a fibrinoid matrix with embedded trophoblast. Defective deep remodelling contributes to placental malfunctioning in complications of pregnancy.

Transvaginal laparoscopy.

Transvaginal laparoscopy (TvL) offers an alternative to standard diagnostic laparoscopy in subfertile patients without obvious pelvic pathology. With a specially developed needle-trocar system, access to the pouch of Douglas is gained through a needle puncture of the posterior fornix. Performed under local anaesthesia or sedation with the patient in a dorsal decubitus position and using prewarmed Ringer lactate as a distension medium, TvL allows complete exploration of the tubo-ovarian structures without supplementary manipulation. The combination of transvaginal sonography and transvaginal endoscopy, including minihysteroscopy, TvL, salpingoscopy and chromopertubation test, permits the most complete exploration of the reproductive tract and can be used as a first-line investigation of female fertility in a one-stop infertility clinic. As the transvaginal route offers easy access to the tubes, ovaries and fossa ovarica, some operative procedures are possible. However, in the absence of a panoramic view, these will be limited to minor interventions.

Belgian legislation and the effect of elective single embryo transfer on IVF outcome.

In order to reduce the number of multiple pregnancies following IVF, the Belgian government agreed to reimburse laboratory expenses for six IVF cycles up to the age of 42 years, in exchange for restriction of the number of embryos replaced. Data on assisted reproduction outcome before and after the introduction of this new legislation were analysed retrospectively in terms of implantation, pregnancy and multiple pregnancy rates. After the introduction of the new law, the percentage of single embryo transfer increased from 14 to 49%. Implantation rates were 25.9 and 23% respectively. There was no difference in the overall pregnancy rate before and after the introduction (36 versus 37%). Twin pregnancies, however, decreased from 19 to 3%. These findings indicate that elective single embryo transfer significantly decreases the twin pregnancy rate without a reduction in the overall pregnancy rate.

Endometriosis: modern surgical management to improve fertility.

Endometriosis is a pleiotropic reproductive condition and the lesions visualized at laparoscopy are only one aspect of this disease process. At present, there is no evidence that surgery for endometriosis can cure infertility. The most important surgery in infertility is ovarian surgery. It is generally accepted that, in most cases, the invagination of the cortex results in the formation of an endometriotic pseudocyst. As a consequence, primordial follicles are present at the base of the cyst. Since surgery is of limited value, the utmost care has to be given to conservation of the patient's fertility. Ablative surgery offers advantages over excision of the cyst in terms of less adhesion formation and better preservation of the ovarian reserve. The ablative eversion technique differs from fenestration and drainage by its access through the site of inversion and resection of the fibrotic ring. Using the new technique of transvaginal hydrolaparoscopy, access to the site of pathology in the fossa ovarica is facilitated. Furthermore, the aqueous distension medium keeps the organs afloat and provides a clear delineation between the organs and adhesions allowing atraumatic reconstructive surgery.

Risk and outcome of bowel injury during transvaginal pelvic endoscopy.

OBJECTIVE: To determine the risk and outcome of bowel injury associated with new techniques of transvaginal pelvic endoscopy. DESIGN: A multinational retrospective survey based on confidential, self-reported cases. SETTING: Tertiary referral centers for infertility. PATIENT(S): Infertile patients without obvious pelvic pathology. INTERVENTION(S): Transvaginal hydrolaparoscopy and fertiloscopy. MAIN OUTCOME MEASURE(S): Full-thickness bowel injury. RESULT(S): Thirty-nine responders reported a total of 24 bowel injuries (0.65%) in 3667 procedures. After initial experience, the prevalence of bowel injury was 0.25%. All of the injuries were diagnosed during the procedure. Twenty-two (92%) of the cases were managed without consequences. CONCLUSION(S): The bowel lesion caused by the new techniques of transvaginal pelvic endoscopy tends to be minor and under strict conditions can be treated expectantly.

An appraisal of the role of laparoscopy: past, present, and future.

OBJECTIVE: To review the role of laparoscopy in the management of chronic pelvic pain (CPP). METHOD: A literature search was conducted to obtain a clear perspective on the role of laparoscopy for CPP. RESULTS: Laparoscopy has been widely used as a diagnostic tool in CPP, but often falls short in defining the type and activity of ectopic endometrial-like tissue. Because pelvic endometriosis includes a wide range of lesions, histological confirmation varies greatly. The evaluation of peritoneal endometriosis at laparoscopy can be misleading. In one study 43% of the patients with minimal or mild endometriosis were found at second-look laparoscopy to be free of lesions. Finally, laparoscopy is not without major complications and the risk of undiagnosed bowel injury is likely to be underestimated. CONCLUSION: The diagnosis of endometriosis can no longer be limited to the visual inspection of the pelvis but requires a wider range of investigations to assess the reproductive system and the role of endometriotic lesions and adhesions in CPP.

Transvaginal hydrolaparoscopy but not standard laparoscopy reveals subtle endometriotic adhesions of the ovary.

OBJECTIVE: To determine whether transvaginal hydrolaparoscopy is superior to standard laparoscopy for detection of subtle endometriotic adhesions of the ovary. DESIGN: Videotapes of standard laparoscopy and transvaginal hydrolaparoscopy were viewed by an independent observer in random order and in a blinded manner. SETTING: Tertiary referral centers for infertility. PATIENT(S): Patients with minimal or mild endometriosis (n = 11) and unexplained infertility (n = 10) on standard laparoscopy from a group of 43 patients with infertility who were undergoing both studies. INTERVENTION(S): Transvaginal hydrolaparoscopy followed by standard laparoscopy. MAIN OUTCOME MEASURE(S): Detection of unexplained ovarian adhesions. RESULT(S): Patients with minimal and mild endometriosis and unexplained infertility had significantly more ovarian adhesions on transvaginal hydrolaparoscopy than on standard laparoscopy. The subtle adhesions seen on transvaginal hydrolaparoscopy but not on standard laparoscopy were filmy, microvascularized, and nonconnecting. CONCLUSION(S): Unexplained ovarian adhesions are frequently detected on transvaginal hydrolaparoscopy but not on standard laparoscopy in infertile patients with minimal and mild endometriosis and unexplained infertility.

An appraisal of the role of laparoscopy: past, present, and future.

OBJECTIVE: To review the role of laparoscopy in the management of chronic pelvic pain (CPP). METHOD: A literature search was conducted to obtain a clear perspective on the role of laparoscopy for CPP. RESULTS: Laparoscopy has been widely used as a diagnostic tool in CPP, but often falls short in defining the type and activity of ectopic endometrial-like tissue. Because pelvic endometriosis includes a wide range of lesions, histological confirmation varies greatly. The evaluation of peritoneal endometriosis at laparoscopy can be misleading. In one study 43% of the patients with minimal or mild endometriosis were found at second-look laparoscopy to be free of lesions. Finally, laparoscopy is not without major complications and the risk of undiagnosed bowel injury is likely to be underestimated. CONCLUSION: The diagnosis of endometriosis can no longer be limited to the visual inspection of the pelvis but requires a wider range of investigations to assess the reproductive system and the role of endometriotic lesions and adhesions in CPP.