Embryo migration following ART documented by 2D/3D ultrasound.

Embryos have traditionally been thought to implant at the exact site they are transferred during assisted reproductive technology (ART). The introduction of 2D/3D ultrasound has allowed for mapping of the transfer site using air bubbles as a surrogate marker of embryo location. This study's aim was to compare the location of embryo transfer (ET) on ultrasound to that of embryo implantation. We present four cases of ectopic pregnancy at four sites: tubal, cervical, interstitial and ovarian. We compare the site of implantation on 2D/3D ultrasound at six weeks of pregnancy to that of transfer as assessed on 2D/3D ultrasound. In all four cases, the embryo flash was visualised in the centre of the uterine cavity on ultrasound at ET. At six weeks of pregnancy, the uterine cavity was empty and an ectopic pregnancy was identified. The tubal and ovarian ectopics were managed surgically whilst the cervical and interstitial pregnancies were treated with systemic methotrexate. These cases demonstrate embryo implantation distal to the ultrasound-confirmed site of transfer. These cases provide visually compelling evidence of embryo migration following ET and lend support to the theory that ectopic pregnancy may occur as a result of embryo migration, rather than poor ET technique.

Reproductive Implications and Management of Congenital Uterine Anomalies: Scientific Impact Paper No. 62 November 2019.

Congenital uterine anomalies (CUAs) are malformations of the womb that develop during fetal life. When a baby girl is in her mother's womb, her womb develops as two separate halves from two tubular structures called 'müllerian ducts', which fuse together before she is born. Abnormalities that occur during the baby's development can be variable from complete absence of a womb through to more subtle anomalies, which are classified into specific categories. While conventional ultrasound is good in screening for CUAs, 3D ultrasound is used to confirm a diagnosis. If a complex womb abnormality is suspected, MRI scanning may also be used, with a combination of laparoscopy in which a camera is inserted into the cavity of the abdomen, and hysteroscopy, when the camera is placed in the womb cavity. As there can be a link between CUAs and abnormalities of the kidney and bladder, scans of these organs are also usually requested. Although CUAs are present at birth, adult women typically do not have any symptoms, although some may experience painful periods. Most cases of CUA do not cause a woman to have difficulty in becoming pregnant and the outcome of pregnancy is good. However, these womb anomalies are often discovered during investigations for infertility or miscarriage. Moreover, depending upon the type and severity of CUA, there may be increased risk of first and second trimester miscarriages, preterm birth, poor growth of the baby in the mother's womb (fetal growth restriction), pre-eclampsia and difficult positioning of the baby for birth (fetal malpresentation). Surgical treatment is only recommended to a woman who has had recurrent miscarriages and has a septate uterus, i.e., the womb cavity is divided by a partition. In this case, surgery may improve her chances for a successful pregnancy, although the risks of surgery, especially scarring of the womb should be considered. However, further evidence from randomised controlled trials are required to provide conclusive evidence-based recommendations for surgical treatment for septate uterus. Surgical treatment for other types of CUAs is not usually recommended as the risks outweigh potential benefits, and evidence for any benefits is lacking. Women with CUAs may be at an increased risk of preterm birth even after surgical treatment for a septate uterus. These women, if suspected to be at an increased risk of preterm birth based on the severity of CUA, should be followed up using an appropriate protocol for preterm birth as outlined in UK Preterm Birth Clinical Network Guidance.1 >.

Cervical cerclage in twin pregnancy.

Cervical cerclage in women with twin pregnancy is not routinely indicated but appears to be beneficial in subjects with a history of preterm birth or very short cervix or dilated cervix. There is a paucity of literature data regarding transabdominal or laparoscopic cervical cerclage (LCC) in twin pregnancy. It is uncertain whether LCC is more effective than transvaginal cerclage. Our own experience of 24 cases of LCC in twin pregnancy showed encouraging results. Further, well-planned studies are required to answer whether, when, and how cervical cerclage should be performed in women with twin pregnancy.

Do specific ultrasonography features identified at the time of early pregnancy loss predict fetal chromosomal abnormality? - A systematic review and meta-analysis.

To investigate the association of specific ultrasonography features identified during the diagnosis of early pregnancy loss (EPL) and abnormal karyotype. This was a systematic review and meta-analysis conducted in accordance with PRISMA criteria. We searched PubMed, Cochrane and Ovid MEDLINE from 1977 to Jan 2017 to identify the articles that described EPL with karyotype and ultrasonography features. Risk differences were pooled to estimate the chromosomal abnormality rates in ultrasonography features, including pre-embryonic, enlarged yolk sac (YS), short crown rump length (CRL), small gestational sac (GS), symmetrical arrested growth embryo, or gestational sac with only a YS. Quality assessment of included studies was performed using Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklists for Observational Studies (2007 version). Thirteen studies were included in the meta-analysis. Chromosomal abnormality was more likely to occur in embryonic EPL and enlarged YS. On the other hand, short CRL, small GS, symmetrical arrested growth embryo, or gestational sac with only a YS, were not associated with an increased risk of fetal chromosomal abnormality. Ultrasonography features at the time of diagnosis of EPL have limited predictive value of fetal chromosomal abnormality.

Prevention of postoperative adhesion reformation by intermittent intrauterine balloon therapy: a randomised controlled trial.

OBJECTIVE: To compare the efficacy of intermittent intrauterine balloon dilatation versus standard care in the prevention of adhesion reformation. DESIGN: Single-blind randomised controlled trial. SETTING: Hysteroscopic Centre of a tertiary University Hospital. POPULATION: Two hundred patients with moderate to severe (European Society for Gynaecological Endoscopy Grade ≥II) intrauterine adhesions who underwent hysteroscopic adhesiolysis. METHODS: All participants were randomised to a balloon group or a control group postoperatively. The balloon group received intrauterine balloon dilatation therapy at 2 weeks and 6 weeks after surgery, whereas the control group did not. All patients underwent follow-up hysteroscopy at 4 and 8 weeks postoperatively. MAIN OUTCOME MEASURES: The adhesion reformation rate and the Pictorial Blood Loss Assessment Chart scores were analysed. RESULTS: A total of 191 patients successfully completed the study protocol (94 cases for the balloon group and 97 cases for the control group). According to hysteroscopic evaluation at the 8th week, the overall adhesion reformation rate was significantly lower in patients in the balloon group than patients in the control group (20.2% versus 40.2%, respectively; P < 0.05). There was also a significant increase in menstruation flow, as assessed by the Pictorial Blood Loss Assessment Chart score (30 versus 9, respectively; P < 0.001). CONCLUSIONS: Postoperative intermittent intrauterine balloon dilatation therapy can significantly reduce postoperative adhesion reformation and significantly increase menstruation flow. TWEETABLE ABSTRACT: RCT: Postoperative intermittent intrauterine balloon therapy can prevent adhesion reformation after hysteroscopic adhesiolysis.

A prospective observational study on the stress levels at the time of embryo transfer and pregnancy testing following in vitro fertilisation treatment: a comparison between women with different treatment outcomes.

OBJECTIVE: To ascertain whether stress biomarkers and psychological indices of stress may predict both conception and miscarriage rates in women undergoing in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI). DESIGN: Prospective observational study. SETTING: A university-affiliated tertiary hospital. POPULATION: Infertile women who were undergoing fresh or frozen IVF/ICSI cycles. METHODS: Women were recruited to (1) complete validated psychological questionnaires (visual analogue scale of stress, state-trait anxiety inventory, perceived stress scale, fertility problem inventory, Beck depression inventory, and general health questionnaire), at the time of embryo transfer (ET) and pregnancy testing (PT), and (2) provide saliva samples for α-amylase (sAA) measurement before and after ET and at PT. MAIN OUTCOME MEASURES: Women were grouped according to subsequent reproductive outcome; scores/levels of all tests were then compared between groups at each time-point. RESULTS: In all, 197 women completed the study, of which 92 conceived and 28 miscarried. The level of psychological stress, as measured by questionnaires, was highest at the time of PT, whereas the level of biological stress as measured by sAA level (IU/l) post-ET (1.8 × 105  ± 1.5 × 105 ) was significantly (P < 0.001) higher than pre-ET (1.2 × 105  ± 1.0 × 105 ) and at PT (1.0 × 105  ± 1.1 × 105 ). However, there was no difference in psychological scoring and in sAA levels between women who did or did not conceive and who had miscarried or had an ongoing pregnancy. CONCLUSIONS: The level of sAA is highest following ET, whereas psychological stress is highest at PT. However, neither stress level appeared to be of prognostic value in predicting conception or miscarriage. TWEETABLE ABSTRACT: Stress level fluctuated at different time-points, but it did not predict conception or miscarriage.

How often does the embryo implant at the location to which it was transferred?

OBJECTIVE: To determine how often the embryo implants exactly at the site of transfer and what additional factors may affect the eventual site of implantation in assisted reproductive technology (ART) cycles. METHODS: This was a prospective observational study of women undergoing ART treatment in a tertiary university unit. Several factors inherent to the embryo transfer (ET), such as the location of the air bubbles and uterine contractility at 1 and at 60 min after ET were assessed with two-dimensional and three-dimensional (3D) ultrasound. In women in whom there was a resulting pregnancy, the position of the gestational sac (i.e. right, left, center or low) was subsequently assessed using 3D ultrasound, and predictors of its location were evaluated. RESULTS: Of 239 recruited women with visualization of air bubbles at ET, 71 singleton gestational sacs were subsequently observed on 3D ultrasound. Overall, 40.8% (29/71) of embryos implanted at the location where the air bubbles were visualized at 1 min after ET, and 50.7% (36/71) implanted where the air bubbles were visualized at 60 min after ET (Cohen's kappa coefficients 0.21 and 0.37, respectively; comparison of agreement values: P = 0.28). Specifically, at 1 min the correspondence between the location of the air bubble and embryo implantation was 37.5% (6/16), 57.1% (8/14), 36.8% (7/19) and 36.4% (8/22) for right, left, central and lower uterus, respectively (4 × 4 contingency table, P < 0.01); at 60 min, the correspondence was 72.2% (13/18), 50.0% (9/18), 33.3% (8/24) and 85.7% (6/7), respectively (5 × 4 contingency table, P < 0.001). In addition, higher vs lower frequency of uterine contractions at 60 min was associated with different sites of implantation (5.6% (1/18), 11.1% (2/18), 27.8% (5/18) and 55.6% (10/18) vs 34.0% (18/53), 24.5% (13/53), 13.2% (7/53) and 28.3% (15/53) for right, left, central and lower uterus, respectively, P < 0.05). In particular, a high uterine contraction frequency following ET was associated with a twofold increased chance of the pregnancy implanting in the lower part of the uterine cavity (relative risk, 1.96 (95% CI, 1.08-3.56), P < 0.05). CONCLUSIONS: The position of the air bubbles within the first 60 min of ET appears to predict the site of implantation in approximately half of cases, denoting an overall poor agreement. This implies significant embryo migration, and has important clinical implications, as it demonstrates that other factors such as uterine contractility may dictate where the embryo will eventually implant following transfer. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

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.

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

BACKGROUND: Several studies have investigated plasma androgen levels in women with recurrent miscarriage (RM) with conflicting results on whether an association between hyperandrogenaemia and RM exists. However, none of these studies included sensitive androgen measurements using a large data set. We therefore investigated the free androgen index (FAI) in a large number of women with RM in order to ascertain whether hyperandrogenaemia is a predictor of subsequent pregnancy outcome. METHODS: We studied 571 women who attended the Recurrent Miscarriage Clinic in Sheffield and presented with > or =3 consecutive miscarriages. Serum levels of total testosterone and sex hormone-binding globulin were measured in the early follicular phase and FAI was then deduced. RESULTS: The prevalence of hyperandrogenaemia in RM was 11% and in a subsequent pregnancy, the miscarriage rate was significantly higher in the raised FAI group (miscarriage rates of 68% and 40% for FAI > 5 and FAI < or = 5 respectively, P = 0.002). CONCLUSIONS: An elevated FAI appears to be a prognostic factor for a subsequent miscarriage in women with RM and is a more significant predictor of subsequent miscarriage than an advanced maternal age (> or =40 years) or a high number (> or =6) of previous miscarriages in this study.