Diagnosis of Congenital Uterine Abnormalities: Practical Considerations.

As most congenital uterine abnormalities are asymptomatic, the majority of them are detected incidentally. While most women with uterine anomalies have a normal reproductive outcome, some may experience adverse reproductive outcomes. Accurate diagnosis and correct classification help in the appropriate counselling of women about their potential reproductive prognosis and risks and for planning any intervention. Evaluation of the internal and external contours of the uterus is the key in making a diagnosis and correctly classifying a uterine anomaly. Considering this, the gold standard test has been the combined laparoscopy and hysteroscopy historically, albeit invasive. However, 3D ultrasound has now become the diagnostic modality of choice for uterine anomalies due to its high degree of diagnostic accuracy, less invasive nature and it being comparatively less expensive. While 2D ultrasound and HSG are adequate for screening for uterine anomalies, MRI and combined laparoscopy and hysteroscopy are reserved for diagnosing complex Mullerian anomalies. Imaging for renal anomalies is recommended if a uterine anomaly is diagnosed.

Ultrasound guidance in reproductive surgery.

Ultrasound plays a key role in diagnosis and guidance in reproductive medicine and surgery. In the field of reproductive surgery, some of the interventions, especially intrauterine procedures, are regularly conducted without imaging guidance but instead performed based on clinical skills and experience alone. Operative real-time US provides concurrent visualisation of the structures, contents and planes and operating instruments and, therefore, has the potential to improve efficacy and safety of the operative interventions. Ultrasound should be used in our operating theatres more often to guide various intrauterine procedures to reduce the intra-operative risks and complications including uterine perforations and visceral injury. The use of ultrasound necessitates an additional assistant experienced in ultrasound in the theatre, but regular use of ultrasound improves the training opportunities of the trainees and clinicians.

Assessment of the uterus with three-dimensional ultrasound in women undergoing ART.

BACKGROUND: A detailed assessment of the uterus forms a pivotal part of the ART treatment process. The emergence of three-dimensional ultrasound (3D US) has provided clinicians with a highly powerful tool in this respect. Assessments with 3D US range from the reconstruction of anatomical planes elusive to conventional US, to the objective measurement of anatomical volumes and vascularization parameters. However, despite the ever increasing number of publications emerging in the literature, the question of which aspects of 3D US are of most clinical value remains a topic of debate. OBJECTIVE AND RATIONALE: The objective of this review is to dissect which aspects of the 3D US assessment of the uterus are supported by a strong level of evidence to date, and should therefore be incorporated into current routine clinical practice. SEARCH METHODS: We conducted a systematic search of the PubMed database up to May 2016, using a combination of text words and Medical Subject Headings (MeSH) pertaining to the 3D US assessment of the uterus. All articles published in the English language were screened to ascertain relevance to women of reproductive age; further citations were retrieved through manual reference list searching. OUTCOMES: A multitude of predominantly observational studies were identified, which concerned a vast variety of 3D US uterine assessments. All articles unequivocally praised the non-invasive, cost-effective, highly acceptable and objective nature of 3D US. Studies regarding the value of assessing the endometrial volume and vascularization prior to embryo transfer appeared conflicting and inconsistent. Studies regarding the imaging of uterine pathology and identification of intratubal and intrauterine devices consistently reported high rates of diagnostic accuracy. A recent RCT did not show an improvement in clinical outcomes when comparing 3D versus 2D US during embryo transfer. However, preliminary studies suggested that 3D US is superior in determining the site of implantation, particularly in ambiguous cases such as interstitial and angular pregnancies. Finally, pilot studies have suggested that the further integration of 3D and possibly 4D US with surgical interventions of the uterus may be a promising prospect. WIDER IMPLICATIONS: 3D US may prove to be an invaluable tool in the assessment of the uterus within the context of ART. Currently, the aim should be to highlight the aspects of 3D US that are most evidence-based and valuable for patients, and to incorporate these into routine clinical practice.

Pregnancy outcomes in oocyte recipients with fibroids not impinging uterine cavity.

OBJECTIVE: To examine the effects of fibroid uterus on pregnancy outcomes and endometrial features in ovum donation recipients. METHODS: Retrospective analysis of 744 ovum donation cycles was conducted in two private IVF centers between 2005 and 2012. All the recipients underwent transvaginal ultrasound examination, including endometrial thickness and grade measurements. Clinical pregnancy, spontaneous miscarriage, and live birth rates were regarded as the primary outcomes. RESULTS: Leimyomas not distorting the uterine cavity were diagnosed in 264 (35.5%) of the cycles. This group exhibited lower endometrial thickness (8.33 ± 1.8 vs. 8.73 ± 2.03 mm, p = 0.009), lower rates of Grade A (16.1 vs. 30.1%, p < 0.0001), and higher rates of grade C endometrium (10.2 vs. 5.5%, p < 0.0001), compared to the group with sonographically normal uterine cavity. In addition, significantly higher spontaneous miscarriage rates were found in fibroid uteri group (25 vs. 14.5%, p = 0.036). CONCLUSION: Our study results suggest that uterine fibroids not distorting the uterine cavity could constitute a risk factor for spontaneous miscarriage in oocyte donation cycles, possibly via their adverse effect on endometrial receptivity. Further well-designed trials should widely explore this subject, particularly focusing on impact of myomectomy on fertility rates in these patients.

Transvaginal ultrasound-guided aspiration of an anterior sacral meningocele masquerading as a hydrosalpinx, resulting in abscess formation.

Anterior sacral meningoceles (ASMs) have a recognized association with a number of connective tissue disorders, including Marfan's syndrome, neurofibromatosis Type 1 and Ehlers-Danlos syndrome. We present the case of a patient with Marfan's syndrome and ASMs who was referred to gynaecology owing to dysmenorrhoea and left-sided pelvic pain radiating to the left leg. A transvaginal ultrasound scan (TVUS) detected a left pelvic cystic tubular structure, attributed to a hydrosalpinx, which, in retrospect, likely corresponded to the ASM. The patient went on to have TVUS-guided drainage of this cystic structure, resulting in an ASM abscess. It is difficult to distinguish ASM from the vastly more common hydrosalpinx using TVUS alone, and in patients with an atypical appearing posteriorly positioned cystic pelvic lesion or in the presence of underlying conditions known to be associated with ASMs, MRI should be considered before any interventional procedure to drain the suspected hydrosalpinx transvaginally. The patient was successfully treated using a minimally invasive CT-guided posterior trans-sacral drainage technique.

Effect of local endometrial injury on pregnancy outcomes in ovum donation cycles.

OBJECTIVE: To evaluate the effect of local endometrial injury (LEI) on clinical outcomes in ovum donation recipients. DESIGN: Retrospective cohort analysis of ovum donation cycles conducted from 2005 to 2012. SETTING: Two private IVF centers. PATIENT(S): Total 737 ovum donation cycles. INTERVENTION(S): LEI by endometrial "scratch" with the use of a Pipelle catheter. MAIN OUTCOME MEASURE(S): Clinical pregnancy and live birth rates. RESULT(S): No statistically significant differences were found in clinical pregnancy rates and live birth rates in cycles subjected to LEI compared with those without. Combination of LEI with fibroid uterus resulted with significantly higher clinical pregnancy rates compared with LEI in normal uterine anatomy. CONCLUSION(S): This is the first study done in ovum recipients who underwent LEI by a "scratch" procedure after failed implantation. Unlike most previous reports, which found improved pregnancy rates with the use of "scratch effect" or "minor endometrial injury" after repeated implantation failures in standard IVF with own eggs, we did not find any changes in implantation rates in a population of egg recipients following this procedure. In view of a possible positive effect of LEI in cycles with a previous four or more failures, prospective randomized controlled studies are warranted to better define the target population who may benefit from this intervention.

Three-dimensional Doppler sonography in asymptomatic and symptomatic women after medical termination of pregnancy.

OBJECTIVES: To characterize the 3D Doppler sonographic appearance of the uterine cavity in asymptomatic and symptomatic women after administration of mifepristone and misoprostol for medical termination of pregnancy. METHODS: A prospective observational study was performed. Women admitted for medical termination of pregnancy underwent transvaginal sonography 15 days after the procedure. Volumes were acquired, and offline analyses of the 3D vascularization indices were performed. Outcomes were collected at the follow-up scan and by telephone after the termination. Women were subclassified as asymptomatic or symptomatic according to the presence/absence of fever, vaginal bleeding, abdominal/pelvic pain, and infections. Spotting was defined as any episodic vaginal bleeding that was less than an expected menstruation and not regarded as a symptom. RESULTS: A total of 104 women who underwent medical termination of pregnancy between 6 and 9 weeks' gestation were enrolled in the study. The termination procedure was successful in 98% of cases; among them, 9 women (8.6%) were symptomatic due to bleeding. Two asymptomatic women required surgery; 1 had sonographic evidence of suspected retained products of conception (endometrial thickness ≥ 15 mm or power Doppler vascularization presence). Fifty-seven women (55%) presented with retained products of conception. All the women with suspected retained products regained normal menses; of these, 3 symptomatic women with retained products (2.9%) underwent a 1-month sonographic follow-up. The symptomatic status was not associated with endometrial thickness, 3D intrauterine mass volume, or 2-dimensional (2D) and 3D power Doppler appearances. CONCLUSIONS: The necessity of surgery after medical termination of pregnancy cannot be predicted by sonography. In cases with sonographic evidence of suspected retained products of conception, endometrial thickness, 2D Doppler findings, and the 3D vascularization indices correlated poorly with bleeding symptoms. Long-term follow-up should be considered in symptomatic women, and it can avoid any unnecessary surgical intervention.

Clinical outcomes from a prospective study evaluating the role of ambulation during medical termination of pregnancy.

BACKGROUND: Although induced abortion is one of the most commonly performed gynecological procedures in Great Britain and medical termination of pregnancy is being used more frequently, very little is known about the role of ambulation during the procedure. We sought to compare ambulatory and non-ambulatory groups of patients undergoing medical termination in the hospital setting and determine whether ambulation impacted clinical outcomes. STUDY DESIGN: This was a prospective patient-preference study carried out among 130 women with pregnancies up to 63 days of gestation fulfilling the requirements of the 1967 Abortion Act and undergoing medical termination of pregnancy. The objective was to evaluate the effect of ambulation during medical termination of pregnancy. The women were given the choice to be ambulatory or non-ambulatory throughout the process of medical termination of pregnancy. They received 200 mg oral mifepristone and 800 mcg vaginal misoprostol for the termination procedure. Outcomes measured included time taken to pass the products of conception, first feeling of abdominal cramps, estimated blood loss, time to discharge from the hospital, pain scores and need for analgesia. RESULTS: In both ambulatory and non-ambulatory groups, the mean time taken to pass the products of conception was similar: 230.7 min (118-343.4) and 233.0 min (134.5-331.5) for ambulatory and non-ambulatory patients, respectively. Time to onset of cramps was 75.6 min (29.4-121.8) for ambulatory and 91.7 min (22.2-161.2) for non-ambulatory patients, from administration of misoprostol. Mean estimated blood loss (assessed by weighing the pads as well as blood in bed pan) was less than 100 mL in both groups, and overall, approximately 85% of patients ranked their pain score as 3 or less (on a scale of 0-5). There were no statistically significant differences in the ambulatory versus non-ambulatory groups with regard to clinical outcomes. CONCLUSION: Ambulation during medical termination of pregnancy neither appears to influence the amount of bleeding or pain nor hasten the process of medical termination of pregnancy.

Human ovarian biopsies as a viable source of pre-antral follicles.

BACKGROUND: Our knowledge of the early pre-antral stage of human folliculogenesis is still poor due to small follicle size and the limited availability of human ovarian tissue. Our aim was to determine the utility of ovarian biopsy for pre-antral follicle research. METHODS: Ovarian cortical biopsies were obtained from women (28-46 years old) undergoing elective Caesarean sections or total abdominal hysterectomy/bilateral salpingo-oophorectomy for a variety of benign gynaecological conditions. Follicle isolation and staging was performed according to a well-established protocol, involving enzymatic digestion, isolation using fine needles and image capture analysis software. RNA was also isolated for reverse transcription. RESULTS: More than 351 follicles were retrieved from 19 patients and 249 were classifiable into follicle stages: 80 primordial, 53 transitional, 82 primary, 26 secondary and 8 multilaminar. All samples, except two from women aged over 40 years, yielded follicles. The average yield of classifiable follicles/patient was 13. There was an age-related decline in mean follicle numbers/patient (r(2) = -0.986). Microgram quantities of complementary DNA per follicle were synthesized. CONCLUSIONS: Despite the heterogeneous distribution of follicles throughout the cortex and the significant age-related decline in the numbers of follicles retrieved, biopsy samples of ovarian cortical tissue provide a useful source of pre-antral follicles. This, coupled with the sensitivity of genomic technology, makes this method a viable research approach.

Stage-specific expression of androgen receptor, follicle-stimulating hormone receptor, and anti-Müllerian hormone type II receptor in single, isolated, human preantral follicles: relevance to polycystic ovaries.

CONTEXT: Recent evidence indicates that the increase in follicle numbers seen in polycystic ovary syndrome occurs early in folliculogenesis, with androgens being a likely causative candidate. In primates and sheep, androgen excess in utero results in ovarian changes similar to those in polycystic ovary syndrome. There is also increasing interest in the role of anti-Müllerian hormone (AMH) in early folliculogenesis because AMH knockout mice have an early depletion of their stock of primordial follicles. Initiation and early folliculogenesis may therefore be under negative control by AMH and positive control by androgens. OBJECTIVE: Because AMH signals exclusively through its type II receptor (AMHRII), the aim of this study was to determine and colocalize the stage-specific expression of AMHRII, androgen receptor (AR), and FSH receptor (FSHR) mRNA in individual, well-characterized preantral follicles. METHOD: Follicles were isolated from human ovarian cortex obtained from either oophorectomies or cortical biopsies at cesarean section. Expression of AR, FSHR, and AMHRII mRNA was determined using a nested RT-PCR protocol. RESULTS: AR mRNA was not detected in any primordial follicles but was from the transitional stage onward. The number of AR-positive follicles increased at each progressive growth stage. The expression of AR preceded that of FSHR, and only a small percentage of primary follicles expressed FSHR. AMHRII expression was rarely detected. CONCLUSIONS: This is the first study to identify the expression of AR in human transitional follicles. Results suggest a role for androgens in promoting early follicle growth and challenging the hypothesis that AMH exerts a direct, inhibitory effect on follicles at this stage.

Comparison of follicular vascularization in normal versus polycystic ovaries during in vitro fertilization as measured using 3-dimensional power Doppler ultrasonography.

OBJECTIVE: The growth of the follicles induced by gonadotropins during IVF treatment is accompanied by physiologic angiogenesis, which is essential for the maturation of the oocytes. We describe the IVF-induced changes in the vascularization and compare normal with polycystic ovaries (PCOs). DESIGN: Prospective study. SETTING: Assisted reproductive unit at a university hospital. PATIENT(S): Sixty women who underwent IVF cycles. INTERVENTION(S): The ovarian vascularization was measured after pituitary down-regulation, FSH stimulation, and hCG-injection using three-dimensional power Doppler ultrasonography. MAIN OUTCOME MEASURE(S): The total ovarian vascularization was divided by the number of follicles. RESULT(S): After pituitary suppression, the ovarian vascularization/follicle was lower in polycystic ovary (PCO) patients. During ovarian stimulation, follicles in PCOs required a lesser amount of FSH to acquire the same level of vascularization than the follicles in normal ovaries. In addition, hCG induced an increase in the follicular vascularization in both normal and PCOs. The follicle count correlated with the total vascularized volume in the ovaries throughout the IVF cycle. CONCLUSION(S): Follicles in PCOs seem to be less vascularized than the follicles in normal ovaries after GnRH treatment but not after gonadotropin stimulation. It is possible that restricted blood supply to the follicles in PCO might be associated with the follicular arrest that is observed. We could confirm that follicles in PCO are more sensitive to gonadotropin stimulation than follicles in normal ovaries.

Diagnosing infertility in a district general hospital: a case-note and cost analysis.

This study aimed to observe diagnostic work-up and cost evaluation of infertile couples to identify opportunities for improvement. One hundred and seventy-four new referrals to the gynaecology clinic in a District General Hospital during 1996 and 1997 provided the cohort for analysis. Data from case notes were transferred on to data collection sheets. Data were inputted into SPSS for analysis. Primary infertility accounted for 62% of couples. One hundred and forty-two couples (81.6%) had a definitive diagnosis, and the analyses relate to these couples only. There was no single investigation performed on the whole cohort studied. Semen analysis was undertaken in 80.3% of the couples; couples with suspected male infertility were over four times more likely to have had more than two semen tests (P = 0.0005); 77.5% of couples had FSH and LH tests; and midluteal progesterone was tested in 76.1%. An increased intensity of FSH-LH hormone testing was associated with couples with anovulation (chi(2) = 6.79, P = 0.03). Serial repeat progesterone tended to be given to women with irregular or prolonged cycles (35 days or more), although this tendency was not statistically significant. The most common test for tubal patency was hysterosalpingography. Higher costs are generally associated with diagnosing endometriosis and tubal factor because of the relatively high cost of laparoscopy. The average cost of diagnosis for each patient was pound 365 and ranged from pound 64 to pound 851. In conclusion, a standard protocol of basic investigative procedures should be offered in secondary centres to all couples. Avoiding duplication and unnecessary investigations (for example, serial progesterone) may reduce costs, although offering all couples a standard protocol of tests would probably offset this observation.

Quantification of ovarian power Doppler signal with three-dimensional ultrasonography to predict response during in vitro fertilization.

OBJECTIVE: To evaluate whether power Doppler predicts ovarian response to gonadotrophin stimulation during in vitro fertilization (IVF). METHODS: Forty-five women were divided into low-reserve (n = 12) and normal-reserve (n = 33) ovarian groups, according to antral follicle count. Transvaginal three-dimensional power Doppler ultrasonographic examinations were performed after pituitary downregulation and after gonadotrophin stimulation. The antral follicle count, ovarian volume, vascularization index, flow index, vascularization flow index, and mean gray value were measured and related to the number of oocytes retrieved and the pregnancy rate. RESULTS: The number of oocytes retrieved correlated with the antral follicle count (R =.458, P =.004) and ovarian volume (R =.388, P <.016) but not with vascularization index, flow index, vascularization flow index, or mean gray value after pituitary suppression. There was an increase in vascularization index (P <.017), flow index (P <.001), and vascularization flow index (P <.007) during gonadotrophin stimulation in the normal-ovary group but not in the low-ovarian-reserve group. CONCLUSION: According to our results, quantification of power Doppler signal in the ovaries after pituitary suppression does not provide any additional information to predict the subsequent response to gonadotrophin stimulation during IVF. The increase in ovarian power Doppler signal during gonadotrophin stimulation is related to the antral follicle count observed after pituitary suppression.

Effect of pituitary down-regulation on the ovary before in vitro fertilization as measured using three-dimensional power Doppler ultrasound.

OBJECTIVE: To evaluate the changes taking place in the ovaries during pituitary down-regulation. DESIGN: Prospective observational study of women undergoing IVF treatment. SETTING: A tertiary referral center for assisted reproduction. PATIENT(S): Forty women who received the long buserelin acetate treatment protocol. Transvaginal three-dimensional power Doppler ultrasound examinations before and after pituitary down-regulation. INTERVENTION(S): Ovarian volume, number of follicles, vascularization index (VI), flow index (FI), vascularization flow index (VFI), and mean gray value (MG). RESULT(S): Before the pituitary down-regulation, the dominant ovary was larger in volume and had a lower MG than the nondominant ovary. After the down-regulation, there was a significant decrease in the volume and number of follicles and an increase in MG. After pituitary down-regulation, the dominant and nondominant ovaries did not differ from each other in any of the parameters. Polycystic ovaries were larger than normal ones before and after the down-regulation, without any differences in MG, VI, FI, or VFI. Right and left ovaries did not differ from each other after the down-regulation. CONCLUSION(S): The differences observed between dominant and nondominant ovaries seem to disappear after pituitary down-regulation. In addition, polycystic ovaries were always larger than the normal ones, but no differences could be detected in the stromal brightness or vascularity either before or after the administration of GnRH agonist therapy.

Temporal regulation of the expression of syncytin (HERV-W), maternally imprinted PEG10, and SGCE in human placenta.

Maternally imprinted PEG10 and SGCE, separated by approximately 2.15 Mb from Syncytin (HERV-W) gene at 7q21.3, are implicated in choriocarcinoma and Silver-Russell syndrome. Here we have analyzed the temporal regulation of mRNA expression of these genes in placenta and demonstrate that Syncytin gene activation is highest in term placenta, PEG10, downregulated at early hypoxic phase, and highly activated at 11-12 wk of gestation. In contrast, transcription from SGCE remained unchanged throughout pregnancy, suggesting two neighboring imprinted genes are differentially regulated at very early pregnancy. Additionally, accumulation of two major species of mRNA (8 kb and 3.1 kb) encoded by HERV-W in placenta is regulated: 3.1 kb mRNA level remained unchanged throughout pregnancy, whereas the production of 8 kb species was highest in term placenta. Western blot and immunohistochemical staining of placental tissues with monoclonal antibodies revealed a marked reduction of syncytin glycoprotein synthesis in late pregnancy. Therefore, the relative levels of 3.1 kb and 8 kb mRNAs in trophoblasts could regulate syncytin protein synthesis, possibly by competition of the two mRNA species for translational apparatus.

Side of ovulation and its effects on uterine and ovarian stromal blood flow and reproductive hormones.

OBJECTIVE: Effect of the side of ovulation on uterine, ovarian, and follicular blood flow parameters and various hormone levels. DESIGN: Prospective, observational study. SETTING: Fertility Clinic, St. George's Hospital. PATIENT(S): Nineteen women with regular menstrual cycles. Pulsed Doppler measurements and serum hormonal concentrations during midfollicular, periovulatory, and midluteal phase for three successive cycles. MAIN OUTCOME MEASURE(S): Doppler blood flow and serum hormones. RESULT(S): Doppler blood flow of the ovarian stroma and follicular and uterine arteries showed no differences in the three phases between the right and left sides. Left-side uterine peak systolic velocity (PSV) (right-side PSV, 31.51cm/s; left-side PSV, 37.38 cm/s) during the periovulatory phase tended to be higher in the nondominant ovary; however, this was not quite significant. The serum hormone concentration showed no significant differences. CONCLUSION(S): The side of ovulation did not influence the Doppler blood flow to the ovarian stroma or follicular and uterine arteries. The side of ovulation had no effect on serum FSH, LH, 17beta-estradiol, P, inhibin A, or inhibin B levels.

Intraindividual hormonal variability in ultrasonographically timed successive ovulatory menstrual cycles is detected only in the luteal phase in infertility patients.

OBJECTIVE: To assess intraindividual variation of follicle stimulating hormone, luteinising hormone, estradiol, progesterone, inhibin A, and inhibin B in three successive ovulatory cycles correlated with transvaginal ultrasound monitored morphological changes in the ovary. METHODS: Serial transvaginal color and pulsed Doppler ultrasound and serum hormone analysis were performed during midfollicular, periovulatory, and midluteal phase for three consecutive cycles in 19 patients with normal menstrual cycles. RESULTS: Luteinising hormone and progesterone showed significant differences in the midluteal phase between the 1st and 2nd cycle (luteinising hormone p = 0.007 and progesterone p = 0.02). Progesterone showed a similar significant change (p = 0.013) between the 2nd and 3rd cycle. No significant differences were seen in the midfollicular or periovulatory phases or between the 1st and 3rd cycle. CONCLUSIONS: Luteal phase progesterone and luteinising hormone concentrations showed individual variation in successive cycles suggesting early or late corpus luteolysis. Follicular and periovulatory hormone levels were similar in subsequent ovulatory cycles.