The measurement of CA 125 and placental protein 14 in uterine flushings in women with recurrent miscarriage; relation to endometrial morphology

The concentrations of CA 125 and placental protein 14 (PP14)were measured in uterine flushings obtained throughout the lutealphase of the cycle from eight normal fertile women. The concentrationsof both proteins increased in a similar pattern throughout theluteal phase of the cycle, with the most dramatic increase occurring6 days after their luteinizing hormone surge (day LH +6). However,a greater variation in CA 125 concentrations was seen comparedto that seen for PP14. The concentrations were compared to thoseobtained on day LH + 7 of the cycle from a group (n equals;35) of women with recurrent miscarriage. The ranges in concentrationof PP14 and CA 125 in the flushings of fertile and recurrentmiscarriage patients were very similar. However, a greater proportionof women with recurrent miscarriage (55%) had low concentrations(<5 ng/ml) of PP14 than in the control group (12.5%) andthe concentrations of PP14 in the uterine flushings were significantlyless (P < 0.05) in women with recurrent miscarriage comparedto the normal fertile group. There was no significant differencein the concentrationof CA 125 in the uterine flushings betweenthe two groups. Histological observation of the endometrialbiopsy samples from recurrent miscarriage patients gave menstrualcycle datings that ranged from day LH +2.5 to LH +6.5 with retardedendometrium (;day LH +5) in 12 of 35 (34%) patients. Of these12 patients, 10 (83%) had low PP14 concentrations and six (50%)had low CA 125 concentrations in their uterine flushings. Inthe recurrent miscarriage patients with histologically normal(sequals; day LH +5) endometrial development, 10 out of 23 (43%)also had low PP14 concentrations and 8 out of 23 (35%) had lowCA 125 in their uterine flushings. The results suggest thatPP14 is better than CA 125 as a marker for endometrial functionin this group of women. In some cases (52%) the low concentrationsof PP14 in the uterine flushings couldbe explained by retardedendometrial development but for the others the reduction inPP14 concentration in the uterine flushing was not associatedwith retardation of endometrial development.     

An analysis of the outcome of microsurgical and laparoscopic adhesiolysis for infertility

We evaluated 81 women with adnexal adhesions and no male factorwho underwent microsurgical (n = 59) and laparoscopic (n = 22)adhesiolysis for infertility. The cumulative conception ratesfor all 81 patients at 12 and 24 months were 41 and 44% respectively.The impact of the following variables on cumulative conceptionrates for all patients was examined: age, duration of infertility,type of infertility, ovulatory status, presence and stage ofendometriosis, adhesion grade, adnexal status (bilateral orunilateral disease, unilateral tubal absence), history of previoussurgery, history of pelvic inflammatory disease and treatmentmodality (microsurgical versus laparoscopic). The results ofindependent comparisons of subgroups within each of these variablesmay be biased because of the interrelationships between thevariables. To overcome this problem, a stepwise Cox's proportionalhazards regression analysis was employed. Our analysis showedthat the single most significant variable influencing the cumulativeconception rates was the duration of infertility (P < 0.005).For every additional year of infertility, the probability ofpregnancy after adhesiolysis (microsurgical or laparoscopic)was reduced by 20%. Cumulative conception rates at 12 and 24months after microsurgical adhesiolysis were 36 and 40% respectively,while after laparoscopic adhesiolysis they were 57% at 12 and24 months. When imbalances were adjusted between the two treatmentgroups, there was no statistically significant difference betweenthe cumulative conception rates for microsurgical and laparoscopicadhesiolysis.     

A reappraisal of the role of polycystic ovary syndrome in recurrent miscarriage

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is associated with recurrent miscarriage. Despite the many studies that have investigated the prevalence of PCOS in recurrent miscarriage, the extent to which PCOS contributes remains highly uncertain. The majority of these studies have used the polycystic ovary morphology alone to define PCOS and the results are extremely variable due to a variety of diagnostic and selection criteria used. Only a very small number of studies have investigated the prevalence of hyperandrogenaemia in recurrent miscarriage. Most crucially, to the authors' knowledge, there is not yet a single publication which has investigated the true prevalence of the complete syndrome of PCOS in recurrent miscarriage using the Rotterdam criteria. Hence there is an urgent need to reappraise the prevalence of PCOS in recurrent miscarriage using the Rotterdam criteria. The possible mechanisms by which PCOS could cause recurrent miscarriage are considered: hyperandrogenaemia, obesity and hyperinsulinaemia are the most likely candidates, although further work is clearly needed. This paper also reviews the possible treatment options for women diagnosed with recurrent miscarriage associated with PCOS. There is some evidence to suggest that weight loss, ovarian drilling and metformin could help to reduce the rate of miscarriage.     

The importance of preconception counseling and early pregnancy monitoring

Preconception counseling plays a key role in preparing for a pregnancy. In couples with a history of recurrent early pregnancy loss, counseling is of particular importance because women are invariably more distressed and require reassurance that everything possible is being done to avoid future pregnancy losses. Because their subsequent pregnancies are more likely to be planned and these patients may be more willing to adopt recommendations that have been offered to them, it becomes more important to identify which investigations and interventions are the most beneficial. Several interventions ranging from genetic testing to lifestyle changes and medications may have a positive effect on the chances of a successful pregnancy. Early pregnancy monitoring and support increases the chance of a live birth and helps to predict potential future pregnancy complications. Recent research suggests that events that occur in the uterine decidua, even before a woman knows she is pregnant, may have a significant impact on fetal growth and the outcome of pregnancy. With this in mind, shifting future research and clinical practice to focus on the periconceptual period and the very early stages of pregnancy should offer significant benefits to the health of both the mother and her infant. The overall aim should be to effectively use every pregnancy as the health-care opportunity of two lifetimes.     

Auto–Cross-Linked Hyaluronic Acid Gel for Prevention of Intrauterine Adhesions after Hysteroscopic Adhesiolysis: A Randomized Controlled Trial

Study ObjectiveTo investigate auto–cross-linked hyaluronic acid gel for the prevention of intrauterine adhesion (IUA) recurrence after hysteroscopic adhesiolysis.DesignA single-center, double-blinded randomized controlled trial.SettingA tertiary university hospital.PatientsTwo hundred seventy-two patients with moderate-to-severe (American Fertility Society [AFS] score ≥5) IUAs underwent hysteroscopic adhesiolysis.InterventionsThe patients were randomized to receive standard care along with auto–cross-linked hyaluronic acid gel after surgery (treatment group) or standard care only (control group). All patients had second-look hysteroscopy at 4 weeks and hormonal therapy for 2 cycles after surgery.Measurements and Main ResultsTwo hundred sixty patients were eligible and randomized; 245 patients successfully completed the study (n = 122 in treatment group, and n = 123 in control group). The primary outcome measure was IUA recurrence at second-look hysteroscopy. The secondary outcome measures included an improvement in the AFS score and menstrual pattern. There was no significant difference with regard to IUA recurrence (31.1% vs 39.8%) or median AFS score at second-look hysteroscopy (2, interquartile range 2, 3, 4 vs 2, interquartile range 2, 3, 4) or improvement in the menstrual pattern at 3-month follow-up (87.7% vs 76.4%), in the treatment and control groups, respectively.ConclusionThe application of auto–cross-linked hyaluronic acid gel did not seem to improve IUA recurrence after hysteroscopic adhesiolysis.     

Does free androgen index predict subsequent pregnancy outcome in women with recurrent miscarriage?

BACKGROUND: Several studies have investigated plasma androgen levels inwomen with recurrent miscarriage (RM) with conflicting resultson whether an association between hyperandrogenaemia and RMexists. However, none of these studies included sensitive androgenmeasurements using a large data set. We therefore investigatedthe free androgen index (FAI) in a large number of women withRM in order to ascertain whether hyperandrogenaemia is a predictorof subsequent pregnancy outcome. METHODS: We studied 571 women who attended the Recurrent MiscarriageClinic in Sheffield and presented with 3 consecutive miscarriages.Serum levels of total testosterone and sex hormone-binding globulinwere measured in the early follicular phase and FAI was thendeduced. RESULTS: The prevalence of hyperandrogenaemia in RM was 11% and in asubsequent pregnancy, the miscarriage rate was significantlyhigher in the raised FAI group (miscarriage rates of 68% and40% for FAI > 5 and FAI 5 respectively, P = 0.002). CONCLUSIONS: An elevated FAI appears to be a prognostic factor for a subsequentmiscarriage in women with RM and is a more significant predictorof subsequent miscarriage than an advanced maternal age (40years) or a high number (6) of previous miscarriages in thisstudy.     

Unexplained recurrent miscarriage: how can we explain it?

Unexplained recurrent miscarriage (RM) can be a challenging and frustrating condition for both patients and clinicians. For the former, there is no diagnosis available for consolation, while for the latter there is little evidence-based treatment to offer. However, the majority of these patients have an excellent prognosis without the need for any treatment. Epidemiological associations suggest that the reason for this is that the majority of women with unexplained RM are in fact healthy individuals, with no underlying pathology, who have suffered three miscarriages purely by chance. Nevertheless, a certain proportion of women with unexplained RM will continue to miscarry, and preliminary studies suggest the presence of pathology in some women of this group. As a result, two types of unexplained RM can be described: Type I unexplained RM, which occurs by chance in women who have no underlying pathology and has a good prognosis; and Type II unexplained RM, which occurs due to an underlying pathology that is currently not yet identified by routine clinical investigations and has a poorer prognosis. Distinguishing between Types I and II unexplained RM can be achieved by considering several factors: the age of the woman, the definition used for RM (i.e. whether biochemical pregnancy losses are considered as miscarriages), the number of previous miscarriages suffered and the karyotype of the products of conception, where available. A better understanding of the two types of unexplained RM could lead to more targeted referrals, investigations and treatments, which would improve cost-effectiveness and overall clinical care.     

Abstracts of the 25<Superscript>th</Superscript> Annual Congress of the European Society for Gynaecological Endoscopy (ESGE), 2<Superscript>nd</Superscript>-5<Superscript>th</Superscript> October 2016, Square – Brussels – Belgium

What is the recommended diagnostic work-up of female genital anomalies according to the European Society of Human Reproduction and Embryology (ESHRE)/European Society for Gynaecological Endoscopy (ESGE) system? The ESHRE/ESGE consensus for the diagnosis of female genital anomalies is presented. Accurate diagnosis of congenital anomalies still remains a clinical challenge due to the drawbacks of the previous classification systems and the non-systematic use of diagnostic methods with varying accuracy, with some of them quite inaccurate. Currently, a wide range of non-invasive diagnostic procedures are available, enriching the opportunity to accurately detect the anatomical status of the female genital tract, as well as a new objective and comprehensive classification system with well-described classes and sub-classes. The ESHRE/ESGE Congenital Uterine Anomalies (CONUTA) Working Group established an initiative with the goal of developing a consensus for the diagnosis of female genital anomalies. The CONUTA working group and imaging experts in the field have been appointed to run the project. The consensus is developed based on (1) evaluation of the currently available diagnostic methods and, more specifically, of their characteristics with the use of the experts panel consensus method and of their diagnostic accuracy performing a systematic review of evidence and (2) consensus for (a) the definition of where and how to measure uterine wall thickness and (b) the recommendations for the diagnostic work-up of female genital anomalies, based on the results of the previous evaluation procedure, with the use of the experts panel consensus method. Uterine wall thickness is defined as the distance between interostial line and external uterine profile at the midcoronal plane of the uterus; alternatively, if a coronal plane is not available, the mean anterior and posterior uterine wall thickness at the longitudinal plane could be used. Gynaecological examination and two-dimensional ultrasound (2D US) are recommended for the evaluation of asymptomatic women. Three-dimensional ultrasound (3D US) is recommended for the diagnosis of female genital anomalies in “symptomatic” patients belonging to high-risk groups for the presence of a female genital anomaly and in any asymptomatic woman suspected to have an anomaly from routine avaluation. Magnetic resonance imaging (MRI) and endoscopic evaluation are recommended for the sub-group of patients with suspected complex anomalies or in diagnostic dilemmas. Adolescents with symptoms suggestive for the presence of a female genital anomaly should be thoroughly evaluated with 2D US, 3D US, MRI and endoscopy. The various diagnostic methods should be used in a proper way and evaluated by experts to avoid mis-, over- and underdiagnosis. The role of a combined ultrasound examination and outpatient hysteroscopy should be prospectively evaluated. It is a challenge for further research, based on diagnosis, to objectively evaluate the clinical consequences related to various degrees of uterine deformity.     

How common is polycystic ovary syndrome in recurrent miscarriage?

The association between polycystic ovary syndrome (PCOS) and recurrent miscarriage (RM) has been long established, but the relative importance of this condition as a cause of RM is far from clear. Previous studies on the prevalence of PCOS in RM have been hampered by a lack of objective and universally accepted criteria for the diagnosis of PCOS, resulting in considerable controversy. However, the Rotterdam criteria have since been accepted as the gold standard for diagnosis of PCOS, and therefore these criteria have been used to produce a much clearer and more objective assessment of the prevalence of PCOS in RM. Three hundred women with recurrent miscarriage were studied. A diagnosis of PCOS was established via measurement of cycle length and day 21 serum progesterone, determination of the free androgen index and pelvic ultrasonography. All ultrasound reports prior to publication of the Rotterdam criteria were reviewed, ensuring consistency in the diagnosis of a polycystic ovary. Ultrasound scans of 27 patients confirmed polycystic ovaries with a further 10 scans suggestive of polycystic ovaries, but with insufficient information for the Rotterdam criteria to be applied. Hence, 27–37 (9.0–12%) patients presented with ultrasonographic polycystic ovaries. Using the Rotterdam criteria, 25–30 (8.3–10%) patients had PCOS. It is concluded that the prevalence of PCOS in RM is considerably lower than has previously been accepted.