A healthy 25-year-old woman presents with worsening dysmenorrhea, pain of recent onset in the left lower quadrant, and dyspareunia She has regular menstrual cycles, and her last menstrual period was 3 weeks before presentation How should this patient be evaluated and treated?

Clinical practice. endometriosis

Endometriosis

Endometriosis is defined as the presence of endometrial-type mucosa outside the uterine cavity. Of the proposed pathogenic theories (retrograde menstruation, coelomic metaplasia and Mullerian remnants), none explain all the different types of endometriosis. According to the most convincing model, the retrograde menstruation hypothesis, endometrial fragments reaching the pelvis via transtubal retrograde flow, implant onto the peritoneum and abdominal organs, proliferate and cause chronic inflammation with formation of adhesions. The number and amount of menstrual flows together with genetic and environmental factors determines the degree of phenotypic expression of the disease. Endometriosis is estrogen-dependent, manifests during reproductive years and is associated with pain and infertility. Dysmenorrhoea, deep dyspareunia, dyschezia and dysuria are the most frequently reported symptoms. Standard diagnosis is carried out by direct visualization and histologic examination of lesions. Pain can be treated by excising peritoneal implants, deep nodules and ovarian cysts, or inducing lesion suppression by abolishing ovulation and menstruation through hormonal manipulation with progestins, oral contraceptives and gonadotropin-releasing hormone agonists. Medical therapy is symptomatic, not cytoreductive; surgery is associated with high recurrence rates. Although lesion eradication is considered a fertility-enhancing procedure, the benefit on reproductive performance is moderate. Assisted reproductive technologies constitute a valid alternative. Endometriosis is associated with a 50% increase in the risk of epithelial ovarian cancer, but preventive interventions are feasible.

/pdf/endometriosis-pathogenesis-and-treatment-2d0xxwf9po.pdf

Endometriosis: pathogenesis and treatment

Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities

Decidualization denotes the transformation of endometrial stromal fibroblasts into specialized secretory decidual cells that provide a nutritive and immunoprivileged matrix essential for embryo implantation and placental development. In contrast to most mammals, decidualization of the human endometrium does not require embryo implantation. Instead, this process is driven by the postovulatory rise in progesterone levels and increasing local cAMP production. In response to falling progesterone levels, spontaneous decidualization causes menstrual shedding and cyclic regeneration of the endometrium. A growing body of evidence indicates that the shift from embryonic to maternal control of the decidual process represents a pivotal evolutionary adaptation to the challenge posed by invasive and chromosomally diverse human embryos. This concept is predicated on the ability of decidualizing stromal cells to respond to individual embryos in a manner that either promotes implantation and further development or facilitates early rejection. Furthermore, menstruation and cyclic regeneration involves stem cell recruitment and renders the endometrium intrinsically capable of adapting its decidual response to maximize reproductive success. Here we review the endocrine, paracrine, and autocrine cues that tightly govern this differentiation process. In response to activation of various signaling pathways and genome-wide chromatin remodeling, evolutionarily conserved transcriptional factors gain access to the decidua-specific regulatory circuitry. Once initiated, the decidual process is poised to transit through distinct phenotypic phases that underpin endometrial receptivity, embryo selection, and, ultimately, resolution of pregnancy. We discuss how disorders that subvert the programming, initiation, or progression of decidualization compromise reproductive health and predispose for pregnancy failure.

/pdf/cyclic-decidualization-of-the-human-endometrium-in-1iwdpp6xfx.pdf

Cyclic decidualization of the human endometrium in reproductive health and failure.

background: Although hysteroscopy is frequently used in the management of subfertile women, a systematic review of the evidence
on this subject is lacking.
methods: We summarized and appraised the evidence for the benefit yielded by this procedure. Our systematic search was limited to
randomized and controlled studies. The QUOROM and MOOSE guidelines were followed. Language restrictions were not applied.
results: We identified 30 relevant publications. Hysteroscopic removal of endometrial polyps with a mean diameter of 16 mm detected
by ultrasound doubles the pregnancy rate when compared with diagnostic hysteroscopy and polyp biopsy in patients undergoing intrauterine
insemination, starting 3 months after the surgical intervention [relative risk (RR) ¼ 2.3; 95% confidence interval (CI): 1.6–3.2]. In patients
with one fibroid structure smaller than 4 cm, there was a marginally significant benefit from myomectomy when compared with expectant
management (RR ¼ 1.9; 95% CI: 1.0–3.7). Hysteroscopic metroplasty for septate uterus resulted in fewer pregnancies in patients with subfertility
when compared with those with recurrent pregnancy loss (RR ¼ 0.7; 95% CI: 0.5–0.9). Randomized controlled studies on hysteroscopic treatment of intrauterine adhesions are lacking. Hysteroscopy in the cycle preceding a subsequent IVF attempt nearly doubles
the pregnancy rate in patients with at least two failed IVF attempts compared with starting IVF immediately (RR ¼ 1.7; 95% CI: 1.5–2.0).
conclusions: Scarce evidence on the effectiveness of hysteroscopic surgery in subfertile women with polyps, fibroids, septate uterus
or intrauterine adhesions indicates a potential benefit. More randomized controlled trials are needed before widespread use of hysteroscopic
surgery in the general subfertile population can be justified.

https://biblio.ugent.be/publication/818743/file/1134345.pdf

The effectiveness of hysteroscopy in improving pregnancy rates in subfertile women without other gynaecological symptoms: a systematic review

Placental bed research: I. The placental bed: from spiral arteries remodeling to the great obstetrical syndromes.

The endoscopic localization of endometrial implants in the ovarian chocolate cyst

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.

/pdf/potential-role-of-endometrial-stem-progenitor-cells-in-the-2z6w6f4ooi.pdf

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

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.

https://www.rbmojournal.com/article/S1472-6483(10)60818-8/pdf

Patrick Puttemans

Papers

The effectiveness of hysteroscopy in improving pregnancy rates in subfertile women without other gynaecological symptoms: a systematic review

Placental bed research: I. The placental bed: from spiral arteries remodeling to the great obstetrical syndromes.

The endoscopic localization of endometrial implants in the ovarian chocolate cyst

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

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