Virtual Compared With In-Clinic Transvaginal Ultrasonography for Ovarian Reserve Assessment.

OBJECTIVE: To evaluate noninferiority of virtual transvaginal ultrasonography compared with in-clinic ultrasonography for ovarian reserve assessment. METHODS: We conducted a single-site, head-to-head crossover trial. Participants performed self-administered virtual transvaginal ultrasonography at home, guided by a remote-certified ultrasound technologist, then underwent transvaginal ultrasonography in-clinic with another ultrasound technologist. Participants were women in the greater Boston area interested in evaluating ovarian reserve and recruited through social media, health care referrals, and professional networks. The uterus and ovaries were captured in sagittal and transverse views. These randomized recordings were reviewed by two or three independent, blinded reproductive endocrinologists. The primary outcome was noninferiority of the rate of clinical quality imaging produced at home compared with in clinic. Sample size was selected for greater than 90% power, given the 18% noninferiority margin. Secondary outcomes included antral follicle count equivalency and net promoter score superiority. RESULTS: Fifty-six women were enrolled from December 2020 to May 2021. Participants varied in age (19-35 years), BMI (19.5-33.9), and occupation. Ninety-six percent of virtual and 98% of in-clinic images met "clinical quality." The difference of -2.4% (97.5% CI lower bound -5.5%) was within the noninferiority margin (18%). Antral follicle counts were equivalent across settings, with a difference in follicles (0.23, 95% CI -0.36 to 0.82) within the equivalence margin (2.65). Virtual examinations had superior net promoter scores (58.1 points, 97.5% CI of difference 37.3-79.0, P<.01), indicating greater satisfaction with the virtual experience. CONCLUSION: Virtual transvaginal ultrasonography remotely guided by an ultrasonography technologist is noninferior to in-clinic transvaginal ultrasonography for producing clinical quality images and is equivalent for estimating antral follicle count. Virtual transvaginal ultrasonography had superior patient satisfaction and has potential to significantly expand patient access to fertility care. FUNDING SOURCE: This study was sponsored by Turtle Health. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04687189.

Ovarian reserve assessment in crohn patients of reproductive age.

OBJECTIVES: Crohn's disease (CD) is a repeating bowel disease characterized by remission and exacerbation periods. The disease mostly affects adults of reproductive age. Women with desires to conceive are concerned about the effects of CD on their fertility. To demonstrate the relationship between ovarian reserve and CD anti-Müllerian hormone (AMH) levels, antral follicle count (AFC) and ovarian volüme were evaluated. MATERIAL AND METHODS: The prospective case-controlled study was conducted at a tertiary referral center in Istanbul between March-August 2019. Ovarian functions were evaluated in 50 patients with CD and in 95 healthy women. Serum gonadotropin and AMH levels were determined. AFCs and ovarian volumes were calculated for all subjects. RESULTS: AMH levels were significantly lower in CD patients (2.1 ± 0.8) compared to the control group (3.3 ± 0.9) (p = 0.001). Serum AMH levels were significantly lower in patients with active CD (2.1 ± 0.6) than the CD patients in remission (2.6 ± 0.8) (p = 0.002). Ovarian volumes and AFC values were significantly lower in both ovaries in CD patients compared to the controls (p < 0.05). CONCLUSIONS: AMH levels, ovarian volume and AFC counts, and thus ovarian reserve was shown to be decreased in CD patients of reproductive age compared to healthy control subjects. Because possible effects of inflammatory damage may be seen in newly diagnosed female CD patients who desire to have a child, we believe that CD patients should be comprehensively assessed for ovarian reserve.

An objective volumetric method for assessment of ovarian follicular and luteal vascular flow using colour Doppler ultrasonography.

Our goal was to develop an objective computer-assisted volumetric method of assessing vascular flow from colour Doppler ultrasound data of ovarian structures recorded by free-hand movement. We hypothesized that a vascularity index (ratio of the region of blood flood to the region of ovarian structure) obtained from the three-dimensional volumetric analysis would be more precise (less variable) than conventional two-dimensional analysis of single images in estimating the functional status of the preovulatory follicles and corpus luteum. Doppler ultrasound cineloops of water buffaloes (Bubalus bubalis; n = 22) ovaries were recorded daily from 12 h before GnRH treatment to four days after ovulation. Cineloops were processed using Fiji and Imaris software packages for segmenting the area (two-dimensional analysis) and the volume (three-dimensional analysis) occupied by the blood-flow and associated tissue to calculate the vascularity index. For volumetric measurement, all images in a cineloop were used (i.e., no a-priori selection of images) while for two-dimensional analysis, three images from the region with apparent maximum vascularity were selected. The volumetric method was verified with theoretical ellipsoidal volume of the follicle (r = 0.96 P < 0.01) or corpus luteum (r = 0.58 P = 0.02). The variability in the follicular vascularity index among animals was lower using the volumetric method than two-dimensional analysis (0.018 ±â€¯0.002 vs 0.030 ±â€¯0.005, P < 0.01), while the variability for CL vascularity was similar between methods (P = 0.23). An increase in the follicular vascularity index was detected at 12 h after GnRH treatment using both methods (two-dimensional: 0.030 ±â€¯0.008, P < 0.01; three-dimensional: 0.016 ±â€¯0.006, P < 0.02). Buffaloes that ovulated tended to have a greater increase in 3D vascularity index than non-responding buffaloes (P = 0.06); the two-dimensional method was not able to detect these changes. Using the three-dimensional method, a moderate positive correlation (r = 0.59; P = 0.02) was evident between the follicular vascularity index at 14-16 h after GnRH treatment and follicular diameter. In conclusion, an objective volumetric method for assessing relative ovarian blood flow changes was developed using Doppler ultrasound cineloops recorded by free-hand movement. The 3-dimensional method eliminates the need for a-priori selection of images and is more precise as a result of decreased technical variability.

Possibilities and real meaning of assessment of ovarian reserve.

OBJECTIVE: To summarize the posibilities of diagnosis of diminished ovarian reserve. DESIGN: Survey of contemporary knowledge. SETTINGS: PPCHC, Sanus Jihlava; PPCHC, Sanus Hradec Králové; Reprogenesis, Brno. METHODS: Review of literature. CONCLUSION: Voluntary or involuntary motherhood postmonement to the third decade of woman's life needs presice evaluation of the ovarian reserve before the infertility treatment. Contemporary there are: 1 hormonal tests (basal and dynamic), 2 ultrasonographic markers of ovarian reserve. The most perspective markers of ovarian reserve seems AMH a AFC.

Testing ovarian reserve in pre-menopausal women: why, whom and how?

Numerous social and environmental factors (environmental hazards, social factors such as education and career, higher economic status desired before the decision is made to have children) influence a women's decision to postpone pregnancy until late reproductive age. In turn, age is related to a fall in ovarian reserve. The main goal of testing ovarian reserve is the identification of women with so-called diminished ovarian reserve (DOR). Additionally, it provides assistance in the counselling of women who are planning to use assisted reproductive techniques (ART). This review examines current methods of testing ovarian reserve and their application. The most useful methods of assessing ovarian reserve are ultrasonographic count of ovarian antral follicles (AFC) and serum tests of both the anti-Müllerian hormone (AMH) level and the third-day level of follicle stimulating hormone (FSH). However, there are limitations to the currently used methods of testing ovarian reserve, especially in relation to their specificity and sensitivity. It is also difficult to predict egg quality based on these tests. The value of screening programmes of ovarian reserve is yet to be determined.

Assessment of ovarian follicular dynamics and folliculogenesis associated endocrine profiles following gonadotropin stimulation in the bonnet monkey.

We evaluated ovarian follicular dynamics in bonnet monkeys by employing trans-abdominal ultrasonography. Following the administration of human follicle stimulating hormone (hFSH) and/or human menopausal gonadotropin (hMG), multiple follicular development was assessed and their numbers, size and growth profiles were monitored. The ultrasonograms showed that the follicular antrum appeared distinctly anechoic with well-defined hyperechoic borders. Depending on the type, quantity (12.5-25IU), and duration (6-9days) of hormones administered, the number of developing follicles was 2-12 per ovary with their lowest diameter being 2mm. With continued hormone administration, their numbers and diameters increased; which were more pronounced in animals administered with hFSH than with hMG, with follicles of 6-8mm. Interestingly, human chorionic gonadotropin (hCG) injection (2000-3000IU), when follicles acquiring >6-8mm sizes, induced the maximum expansion of antral follicles with sizes reaching up to 14mm. On days 3-5 post-hCG, the ultrasonograms showed loosely demarcated multiple hypoechoic structures and well-demarcated hyperechoic structures with anechoic/hypoechoic cores corresponding to unruptured luteinized follicles and corpora lutea, respectively. On day 4 post-hCG, there was a substantial reduction in the number of antral follicles. In stimulated animals, follicular growth, ovulation, and formation of luteal structures were accompanied by corresponding physiological changes in the serum estradiol and progesterone profiles. These findings, for the first time, showed that ultrasonographic imaging approach is useful for precise monitoring of temporal changes in follicular developmental dynamics and to time the hCG induced ovulation in the bonnet monkey.

Assessment of follicle viability using fluorescence microscopy before and after ovarian thawing.

The incidence of young women diagnosed with cancer has been globally increasing. In many cases the surgical approach followed by chemotherapy, radiotherapy or hormonal therapy could lead to infertility or premature ovarian failure. Several options are available in order to preserve fertility and increase the future gestation rate. Among embryo cryopreservation and oocyte cryopreservation, ovarian tissue cryopreservation represents an ideal option, especially for premenopausal women and for those who cannot delay the start of chemotherapy. The purpose of this study was to examine the follicle viability using fluorescence microscope before and after ovarian thawing.

Assessment of ovarian reserve in euthyroid adolescents with Hashimoto thyroiditis.

AIM: We aimed to investigate the ovarian function and reserve in euthyroid adolescents (TSH < 2.5 mIU/L) diagnosed with Hashimoto thyroiditis (HT). METHODS: This case-control study included 30 adolescent girls (mean age 15.1 ± 1.4 years) newly diagnosed as HT with presence of high thyroid antibodies with gland heterogeneity in ultrasound and age-matched 30 healthy female subjects. Anti-ovarian antibody (AOAb), LH/FSH ratio, estradiol, anti-mullerian hormone (AMH), inhibin-B, total testosterone, antral follicle count, ovarian volumes and uterine length were measured. The clinical, laboratory, and ultrasound data of the HT and control groups were compared. RESULTS: There were no significant differences between the girls with HT and healthy controls in relation to LH/FSH ratio, estradiol and inhibin-B levels. AOAb (p = 0.02), AMH (p = 0.007) and total testosterone levels were higher in HT group than the control group (p = 0.03). AOAb level was found to be positively correlated with LH/FSH ratio (p = 0.03), AMH (p = 0.01) and inhibin-B (p < 0.001) in HT group. CONCLUSION: This study demonstrated that the adolescent girls diagnosed with autoimmune thyroiditis had normal ovarian reserve based on measurements of AMH, inhibin B, FSH, LH/FSH ratio, estradiol and antral follicle counts.

Comparing transabdominal and transvaginal ultrasound-guided follicular aspiration: A risk assessment formula.

OBJECTIVE: We sought to identify patients at risk of incomplete transvaginal oocyte retrieval, develop a risk assessment formula to identify patients who would benefit from a transabdominal approach, and compare complication and pregnancy rates between these two approaches. MATERIALS AND METHODS: In this retrospective case control study in a private in vitro fertilization center, 95 cases of women undergoing transabdominal follicular aspiration for oocyte retrieval (15 transabdominal only and 80 transabdominal and vaginal combined) were compared with 278 controls of women undergoing the transvaginal aspiration only. Transabdominal oocyte retrieval was performed when one or more ovaries could not be retrieved via the transvaginal approach. Main study outcomes included need for transabdominal retrieval, pregnancy rates, and complications. RESULTS: A risk assessment scoring system was developed as follows: difficulty seeing ovaries on ultrasound (+4), history of pelvic surgery (+3), and body mass index of 30 kg/m(2) or greater (+2). With a cutoff score of 4 or greater, the overall sensitivity is 75%, specificity is 80%, positive predictive value is 57%, and negative predictive value is 90%. No statistically significant differences were found for pregnancy rates or complications. CONCLUSION: The transabdominal approach is an alternative option that would increase the total number of oocytes retrieved with no statistical difference in complication or pregnancy rates. We also developed a scoring system that can serve as a useful screening tool for identifying women at increased risk of transabdominal oocyte retrieval.

Possibilities and limits of ovarian reserve testing in ART.

Markers of ovarian reserve are associated with ovarian aging as they decline with chronologic age, and hence may predict stages of reproductive aging including the menopause transition. Assessment of ovarian reserve include measurement of serum follicle stimulating hormone (FSH), anti-M�llerian hormone (AMH), and inhibin-B. Ultrasound determination of antral follicle count (AFC), ovarian vascularity and ovarian volume also can have a role. The clomiphene citrate challenge test (CCCT), exogenous FSH ovarian reserve test (EFORT), and GnRH-agonist stimulation test (GAST) are dynamic methods that have been used in the past to assess ovarian reserve. In infertile women, ovarian reserve markers can be used to predict low and high oocyte yield and treatment failure in women undergoing in vitro fertilization. However the markers may have limitations when an in depth analysis of their accuracy, cost, convenience, and utility is performed. As ovarian reserve markers may permit the identification of both the extremes of ovarian stimulation, a possible role for their measurement may be in the individualization of treatment strategies in order to reduce the clinical risk of ART along with optimized treatment burden. It is fundamental to clarify the cost/benefit of its use in the ovarian reserve testing before initiation of an IVF cycle and whether the ovarian reserve markers-determined strategy of ovarian stimulation for assisted conception may be associated to improved live birth rate.

Affordable ART: a different perspective.

BACKGROUND: Although ≈ 10% of the population is affected by infertility, the treatment option of in-vitro fertilisation (IVF) remains unaffordable for the majority of infertile couples. We have initiated a lowcost programme incorporating an uncommonly used, but recognized, ovarian stimulation protocol, together with certain costlimiting initiatives in an established assisted reproductive technology (ART) set up. METHODS: The medical records of women who underwent the lowcost programme were analysed. Clomiphene citrate 50 mg daily was administered from Day 2 of the cycle and continued till the day of hCG trigger, thus preventing the LH surge. Intermittent doses of human menopausal gonadotrophin 150 IU were administered on alternate days from the 5th day onwards. Oocyte retrieval was carried out once at least two follicles of >18 mm were identified. The cycle was monitored by ultrasound only, with embryo transfer being carried out on Day 3. Clinical outcomes were recorded together with an estimation of the direct costs per cycle. Direct cost calculations did not include professional charges or facility costs. RESULTS: Of 143 women evaluated, 104 women underwent embryo transfer. The live birth rate and clinical pregnancy rate per embryo transfer were 19 and 22%. The live birth rate per initiated cycle was 14% (20/143). The multiple pregnancy rate was 26% with no case of ovarian hyperstimulation syndrome being recorded. The average direct cost per cycle was US$ 675 for IVF and US$ 725 for an ICSI treatment cycle. CONCLUSIONS: Using this protocol, together with several costcutting measures, we achieved an acceptable live birth rate per transfer of 19% at a reasonable cost. This approach could be used by established ART centres to provide treatment to couples who cannot afford conventional ART.

Assessment of theca cell function prior to controlled ovarian stimulation: the predictive value of serum basal/stimulated steroid levels.

BACKGROUND: Serum androgen levels correlate with ovarian sensitivity to follicle-stimulating hormone (FSH) but in practice, standard baseline serum testosterone (T) levels prior to in-vitro fertilization (IVF) may not be the most appropriate marker for determination. METHODS: Infertile women enrolled in an IVF programme were included in this study. Serum T and Delta4-androstenedione (A), and the androgen precursor 17-hydroxyprogesterone (17-OHP) were measured before and 24 h after a gonadotrophin-releasing hormone agonist stimulation test (GAST). An early follicular phase antral follicle count (AFC) was also performed. Patients were subsequently enrolled in a long gonadotrophin-releasing hormone agonist protocol with a standard FSH dose (150 IU) for 7 days to assess the association between androgen levels and ovarian responsiveness to FSH. RESULTS: The GAST elicited a significant increase in serum androgen levels that was well correlated with AFC. 17-OHP showed the greatest response to GAST and strongest correlation with AFC. The 17-OHP response to GAST differentiated patients with high ovarian reserve (OR) from those with low or normal OR as assessed by AFC, whereas only the estradiol response could differentiate those with low AFC. GAST-stimulated serum levels of 17-OHP were also correlated with ovarian response to FSH. Using receiver operating characteristic curve analysis, stimulated 17-OHP levels were predictive of the ovarian response to controlled ovarian stimulation, with similar power to that observed with AFC but lower power than with anti-Müllerian hormone. CONCLUSIONS: Serum androgen levels following GAST are correlated with AFC and ovarian response to FSH. Serum T is a less sensitive marker of theca cell function than 17-OHP.

Automated assessment of ovarian follicles using a novel three-dimensional ultrasound software.

OBJECTIVE: To evaluate the accuracy, efficiency, and applicability of a new automated method of follicular assessment. DESIGN: Retrospective review of three-dimensional ultrasonographic ovarian volumes. SETTING: Academic center. PATIENT(S): Three-dimensional ovarian volumes from patients undergoing IVF. INTERVENTION(S): Three-dimensional volumes of gonadotropin-stimulated ovaries and simulated ovarian follicles (SOFs) of known volume were evaluated with the new automated follicular assessment software (SonoAVC). MAIN OUTCOME MEASURE(S): [1] Maximum absolute error for the SonoAVC in assessing the volumes of the SOFs; [2] correlations between the automated and manual follicular measurements; [3] time required to analyze all of the follicles in a given ovarian volume. RESULT(S): The SOF of 4, 6, and 10 mm were evaluated. The SonoAVC's maximum absolute error for the volumes of the 4, 6, and 10 mm SOFs was 0 (0%), 0.01 (8.3%), and 0.02 (3.8%) cc, respectively. Three hundred forty-seven follicles, ranging in diameter from 2.3-32 mm, were evaluated. The correlation coefficient for the SonoAVC-generated relaxed follicular diameter and the manual measured mean follicular diameter was 0.99. The time required to analyze all of the follicles in a given ovarian volume for the automated and manual method was 133 versus 361 seconds, respectively. CONCLUSION(S): The SonoAVC proved to be a very accurate and efficient way to measure ovarian follicles. The measurements obtained by the SonoAVC correlated extremely well with the manual measurements we obtained.

Ultrasound assessment of the ovary in the infertile woman.

Few would argue that the introduction of transvaginal ultrasound (TVUS) revolutionized the practice of assisted reproduction. For example, full-bladder follicular scanning and laparoscopic oocyte retrievals were converted to TVUS-guided procedures. The application of higher-frequency scanning probes provided greater resolution and improved the clinician's ability to evaluate the ovary for pathologic conditions, for determination of ovarian reserve, and for therapeutic decisions during ovarian stimulation cycles. All these uses of TVUS of the ovary will be discussed in this article.

Perifollicular vascularity assessment for selecting the best oocytes for in vitro fertilization programs in older patients.

The current prospective, randomized, controlled study aimed to assess the clinical efficacy of the perifollicular vascularity assessment by using power Doppler ultrasonography, as an additive criterion to the standard morphologic ones, for choosing the most competent oocytes. Data obtained from 60 infertile patients who were >40 years of age and were unselected for ovarian reserve showed that this approach does not improve any reproductive outcomes in IVF programs.

Assessment of the intensity of behavioural traits and ovulation between synchronized and non-synchronized cows.

Thirty cyclic, non-suckled Brahman cows were divided into three groups, all of which were synchronized sequentially with CIDR-B and observed continuously for 100 h to determine different behavioural oestrus signs. Twenty-four hours after implant withdrawal, all synchronized cows in the group, together with all other cows displaying oestrus, were subjected to intensive ultrasonographic observations (every 6 h for 120 h) to pinpoint the moment of ovulation. In the first group, oestrus and ovulation response was 60% (6/10), in the second 44% (4/9) showed oestrus and six ovulated, and in the third group oestrus and ovulation were 80% (8/10). Significant differences were observed between the second and third groups (p < 0.05). No differences were observed in the duration of oestrus, time when oestrus was displayed after implant withdrawal, time of ovulation and onset of oestrus, end of oestrus to ovulation, and intensity of oestrus on a point scale. The relationship between duration of oestrus and time of ovulation was r(2) = 0.16. Ovulation, on average, was 32.1 +/- 14.5 h after the onset of oestrus, 22.3 +/- 16.5 h after the end of oestrus, and 91.8 +/- 16.7 after implant withdrawal, although no significant differences were observed. One non-synchronized animal showed oestrous activity in the second group but failed to ovulate. In the third group, 8 animals showed oestrus, 4 with high concentrations of progesterone. Of the other four one ovulated. In conclusion, oestrous behaviour is not necessarily the best marker to predict the time when ovulation takes place due to variation in the length of the oestrous period and the possible integration of non-ovulatory animals into sexually active groups.

Does 3D ultrasound offer any advantage in the pretreatment assessment of ovarian reserve and prediction of outcome after assisted reproduction treatment?

BACKGROUND: This study compared the predictive value of the antral follicle count (AFC) measured from stored 3D data by three methods including a '2D equivalent technique' and two 3D techniques, the 'multiplanar view' and 'rendered inversion mode', as a test of ovarian reserve and treatment outcome. METHODS: One hundred consecutive subjects aged<40 years with basal FSH levels<12 IU/l underwent transvaginal ultrasound in the early follicular phase prior to their first cycle of assisted reproduction treatment. The relationship between the AFC made with each method and outcome was evaluated. RESULTS: The AFC as measured by the 'inversion mode' method (r=0.777) showed a higher, but statistically insignificant, correlation with the number of retrieved oocytes than did comparable measurements made with the '2D equivalent' (r=0.665) and '3D multiplanar' (r=0.687) techniques. Multiple regression analysis showed the AFC measured using any of the three methods was a significantly better predictor of the number of oocytes retrieved (P<0.001) than age, FSH or ovarian volume. AFC was not predictive of non-conception regardless of the measurement technique. CONCLUSIONS: For predicting ovarian respone and outcome, the AFC measured using techniques based on 3D ultrasound offers no statistically significant advantage over a measurement which is limited to information available with conventional 2D imaging.

Power doppler ultrasound assessment of the relationship between age and ovarian perifollicular blood flow in women undergoing in vitro fertilization treatment.

PURPOSE: To examine the relationship between age and ovarian perifollicular blood flow (PFBF) in women undergoing IVF. METHODS: Serial transvaginal power Doppler ultrasound (PDU) scans to assess ovarian PFBF were performed prospectively throughout the follicular phase of ovarian stimulation in women undergoing IVF. The ultrasound assessment days were categorized according to day of hCG trigger. RESULTS: A total of 1050 ovarian follicles from 34 women undergoing one IVF treatment cycle were used for data analysis. The median age of the women was 38.5 years, ranging from 28 years to 44 years. There was a significant negative correlation between age and ovarian PFBF on the day of hCG trigger or trigger day minus 1, but not beforehand during the follicular phase. CONCLUSIONS: There was a significant negative correlation between age and ovarian PFBF in women undergoing IVF which was only observed very late in the follicular phase of ovarian stimulation.