Key content Fibroids are the most common uterine growth and there is an increasing range of options for their management. Management options are affected by the woman's symptoms, age, desire to conceive and local resources. Pharmacological agents are effective in alleviating symptoms and may improve women’s quality of life. Interventional radiology procedures may prevent the need for hysterectomy. Conventional surgical procedures and minimal access surgery are important in management of fibroids. Learning objectives To understand the options available for the management of uterine fibroids. To create awareness of radiological techniques, such as uterine artery embolisation and magnetic resonance imaging‐guided focused ultrasonography, that preserve the uterus. To understand the use of pharmacological agents in the reduction of menstrual blood loss and fibroid size. Ethical issues Is it ethical to offer new minimally invasive treatment options for fibroids to older women who wish to retain potential fertility?
Polycystic ovary syndrome (PCOS) is a common gynaecological disorder, with a prevalence of up to 12% of women of reproductive age, and is in part characterised by elevated circulating androgens and aberrant expression of androgen receptor (AR) in the endometrium. A high percentage of PCOS patients suffer from infertility, a condition that appears to be linked to mistimed and incomplete decidualisation critically affecting events surrounding embryo implantation. The aim of this study was to examine the involvement of MAGEA11, and the genome-wide role of AR in PCOS. We determined that elevated androgen levels on PCOS cells had an impact on the delayed and incomplete decidual transformation of endometrial cells. The AR co-regulator MAGEA11, a known enhancer of AR function, was constitutively overexpressed throughout the menstrual cycle of PCOS patients, co-localised in the nucleus of PCOS stromal tissue and cells and formed a molecular complex with AR. Genome-wide AR analysis in PCOS stromal cells revealed that AR targets included genes involved in cell death and apoptosis, as well as genes commonly dysregulated in endometrial cancer. Enhanced MAGEA11 and AR-mediated transcriptional regulation may impact on a correct endometrial decidualisation response, subsequently affecting endometrial receptivity in these infertile women. Key messages MAGEA11 and AR are overexpressed in hyperandrogenic PCOS patients. MAGEA11-AR overexpression in PCOS correlates with delayed decidualisation. AR and MAGEA11 associate in a molecular complex. AR directly regulates a unique set of genes controlling gene differentiation. Electronic supplementary material The online version of this article (10.1007/s00109-019-01809-6) contains supplementary material, which is available to authorized users.
Endometrial receptivity is mediated by adhesion molecules at the endometrium-trophoblast interface where osteopontin (OPN) and CD44 form a protein complex that plays an important role in embryo recognition. Here, we undertook a prospective study investigating the expression and regulation of OPN and CD44 in 50 fertile and 31 infertile ovulatory polycystic ovarian syndrome (PCOS) patients in the proliferative and secretory phases of the natural menstrual cycle and in 12 infertile anovulatory PCOS patients. Endometrial biopsies and blood samples were evaluated for expression of OPN and CD44 using RT-PCR, immunohistochemistry and ELISA analysis to determine circulating levels of OPN, CD44, TNF-α, IFN-γ and OPN and CD44 levels in biopsy media. Our findings highlighted an increased level of circulating OPN and CD44 in serum from infertile patients that inversely correlated with expression levels in endometrial tissue and positively correlated with levels secreted into biopsy media. OPN and CD44 levels positively correlated to each other in serum and media from fertile and PCOS patients, as well as to circulating TNF-α and IFN-γ. In vitro analysis revealed that hormone treatment induced recruitment of ERα to the OPN and CD44 promoters with a concomitant increase in the expression of these genes. In infertile patients, inflammatory cytokines led to recruitment of NF-κB and STAT1 proteins to the OPN and CD44 promoters, resulting in their overexpression. These observations suggest that the endometrial epithelial OPN-CD44 adhesion complex is deficient in ovulatory PCOS patients and displays an altered stoichiometry in anovulatory patients, which in both cases may perturb apposition. This, together with elevated circulating and local secreted levels of these proteins, may hinder endometrium-trophoblast interactions by saturating OPN and CD44 receptors on the surface of the blastocyst, thereby contributing to the infertility associated with ovulating PCOS patients. Key messages • Endometrial epithelial OPN-CD44 adhesion complex levels are deficient in ovulatory PCOS patients contributing to the endometrial infertility associated with ovulating PCOS patients. • Circulating levels of OPN, CD44 and inflammatory cytokines TNF-α and IFN-γ are altered in infertile PCOS patients. • Increased levels of both OPN and CD44 in biopsy media and serum inversely correlate with endometrial expression of these markers in endometrial tissue. • In infertile PCOS patients, high levels of oestrogens and inflammatory cytokines stimulate the recruitment of transcription factors to the OPN and CD44 promoters to enhance gene transcription. • Our study identifies a novel crosstalk between the CD44-OPN adhesion complex, ERα, STAT1 and NF-κB pathways modulating endometrial receptivity.
Infertility affects 1 in 7 couples in the UK. Tubal patency tests are an important part of infertility investigations. We conducted this observational study to determine the interval between a laparoscopy and dye test and spontaneous conception in women with unexplained infertility and minimal to mild endometriosis and pelvic adhesions treated during the procedure. The clinical records of 432 women coded as having had a laparoscopy and dye test or laparoscopy and tubal patency test between April 2007 and March 2010 were retrieved from a computerised theatre database. Pregnancies were identified through a computerised maternity booking system. Spontaneous pregnancies were recorded in 162 women following surgery (37.5%). There was a significant difference in conception rates between women with unexplained infertility and those with minor abnormalities treated at the time of diagnosis (43% vs. 58%, p = 0.019). Eighty percent of women who conceived spontaneously achieved their pregnancy within 18 months of surgery. A high proportion of women with unexplained infertility or minor abnormalities treated at the time of a laparoscopy and dye test conceived spontaneously within 12 months.
S ubfertility affects 1 in 6 couples in the UK. In the initial GP consultation it is helpful to see both partners together, although this may be difficult in a single 10 minute consultation. In 39% of couples, both male and female factors are responsible for subfertility, with male factors accounting for 30% of subfertility problems. Although this article will focus on female factors, male assessment is important, and a semen sample is one of the first steps in an assessment. If an abnormality is detected in the semen analysis, the test is normally repeated and if confirmed a secondary care referral is required. In 70% of cases a female factor will be the primary cause, and this article will focus on female factors in the more detailed management of subfertility. The GP curriculum and female infertility Clinical module 3.08; Sexual health states that:. General practice has an important role in the management of sexual health problems. A holistic and integrated approach should be taken. Sensitive, non-judgemental communication skills are essential Background and definition Subfertility is defined as the inability of a couple to conceive after 12 months of regular vaginal sexual intercourse (two to three times per week). It may be primary subfertility, where the female partner has never conceived, or secondary subfertility, when the female partner has conceived in the past regardless of the outcome of the pregnancy. Recurrent miscarriage is not discussed in this article, but advice can be found in the Royal College of Obstetricians and Gynaecologists (RCOG) Green top guideline no. 17 (RCOG, 2011). Fertility can be assessed in terms of fecundity, which is the conception rate per menstrual cycle. Female age is an important factor in fertility. Fecundity declines with advancing maternal age: in 19 to 26year-old females the probability of fecundity is 92%, whereas in 35 to 39-year-old females it is 80% after a year of regular intercourse (Dunson, Baird, & Colombo, 2004). Couples should be counselled that 84% of women with a regular menstrual cycle having regular vaginal sexual intercourse will conceive within 12 months, 92% within 2 years and 93% within 3 years (Te Velde, Eikemans, & Habbema, 2000). On this basis, simple reassurance and support may be all that is needed for a young woman with a normal menstrual cycle presenting less than a year after starting to try to conceive. Conversely, a 36-year-old woman or young woman with known risk factors for subfertility will need more prompt investigation and secondary referral (Cutting, Morroll, Roberts, Pickering, & Rutherford, 2008). Female subfertility is broadly divided into anovulation problems (inability to release an egg), tubal factors, and uterine and peritoneal factors (endometriosis, adenomyosis and fibroids). Anovulation contributes to 25% of cases and the most common cause is polycystic ovarian syndrome (PCOS) (National Institute for Health and Care Excellence (NICE), 2016; Thonneau et al., 1991). Tubal factors are responsible for 20% of cases (pelvic inflamma...
A nonpuerperal uterine inversion is a rare occurrence clinically. It is usually associated with uterine fibroids or tumors. We report a case of 47 years old nulliparous women who presented with sudden onset of severe abdominal pain and heavy vaginal bleeding. Speculum examination revealed a 6 cm bleeding mass presenting in the vagina. The case was managed by performing hysterectomy using combined laparoscopic and vaginal routes.
Many women present in general practice with the complaint of excessive hair growth on the face, chest or limbs. This article aims to cover the normal physiology of hair growth, how to define excessive hair growth in a woman, and when it is essential to refer a patient for urgent secondary care advice and further management.
An estimated 8-out-of-10 women experience physiological premenstrual symptoms, 3–30% of these women suffer with symptoms of premenstrual syndrome (PMS) that interfere with daily life, with 1–10% of women suffering from severe PMS symptoms meeting the DSM-5 criteria for diagnosis of premenstrual dysphoric disorder (PMDD). PMDD can be considered a subdivision of PMS and is a combination of psychological, behavioural and physical symptoms that can vary in intensity and presents cyclically during the luteal phase of ovulatory menstrual cycles. The diagnosis of PMDD and PMS depends on the timing of symptoms, the severity of symptoms and their impact on quality of life. Physiological symptoms (feeling bloated, headache, acne, mood changes and constipation) that do not impact on daily activities and quality of life are considered to be physiological premenstrual symptoms rather than PMS. There is no association with age, educational status or employment for PMS or PMDD.
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