Open-source graphical user interface for the creation of synthetic skeletons for medical image analysis.

Purpose: Deformable medial modeling is an inverse skeletonization approach to representing anatomy in medical images, which can be used for statistical shape analysis and assessment of patient-specific anatomical features such as locally varying thickness. It involves deforming a pre-defined synthetic skeleton, or template, to anatomical structures of the same class. The lack of software for creating such skeletons has been a limitation to more widespread use of deformable medial modeling. Therefore, the objective of this work is to present an open-source user interface (UI) for the creation of synthetic skeletons for a range of medial modeling applications in medical imaging. Approach: A UI for interactive design of synthetic skeletons was implemented in 3D Slicer, an open-source medical image analysis application. The steps in synthetic skeleton design include importation and skeletonization of a 3D segmentation, followed by interactive 3D point placement and triangulation of the medial surface such that the desired branching configuration of the anatomical structure's medial axis is achieved. Synthetic skeleton design was evaluated in five clinical applications. Compatibility of the synthetic skeletons with open-source software for deformable medial modeling was tested, and representational accuracy of the deformed medial models was evaluated. Results: Three users designed synthetic skeletons of anatomies with various topologies: the placenta, aortic root wall, mitral valve, cardiac ventricles, and the uterus. The skeletons were compatible with skeleton-first and boundary-first software for deformable medial modeling. The fitted medial models achieved good representational accuracy with respect to the 3D segmentations from which the synthetic skeletons were generated. Conclusions: Synthetic skeleton design has been a practical challenge in leveraging deformable medial modeling for new clinical applications. This work demonstrates an open-source UI for user-friendly design of synthetic skeletons for anatomies with a wide range of topologies.

In vitro fertilization practice in patients with absolute uterine factor undergoing uterus transplant in the United States.

OBJECTIVE: To report detailed, pooled multicenter experiences and outcomes after in vitro fertilization (IVF) treatment among patients undergoing uterus transplantation (UTx) in the US. DESIGN: Cohort study. SETTING: Hospital. PATIENTS: Patients undergoing UTxsfrom the three longest-running UTx clinical trials in the US. INTERVENTION: In vitro fertilization treatment among patients undergoing UTx.. MAIN OUTCOME MEASURES: Reproductive outcomes pretransplant and posttransplant ovarian stimulation. RESULTS: Thirty-one uterus transplant recipients were included in this cohort (mean [±SD] age at transplant was 31 ± 4.7 years). Before transplant, recipients completed a mean of two oocyte retrievals (range 1-4), banking a mean of eight untested embryos (range 3-24) or six euploid embryos (range 2-10). Posttransplant retrieval cycles were required in 19% (n = 6/31) of recipients, for a total of 16 cycles (range 2-4 cycles per recipient). All posttransplant retrievals were performed vaginally without complications. Preimplantation genetic testing was used by 74% (n = 23/31) of subjects. Seventy-two autologous single embryo transfers (ETs) occurred in 23 patients who completed at least one ET. Two ETs followed a fresh IVF treatment cycle, and the remainder (n = 70) were frozen ETs. Endometrial preparation was more commonly performed with programmed protocols (n = 61) (exogenous administration of estrogen and progesterone) compared with natural cycle protocols (n = 9). The overall live birth rate (LBR) for this cohort was 35% (n = 25/72) per ET. Among those patients (n = 21) who had an ET leading to a live birth, a mean of 2.2 ETs were performed. The overall LBR after the first ET was 57% (n = 13/23) and rose to 74% (n = 17/23) after a second ET. There was no difference in rate of preeclampsia, live birth, neonatal birth, or placental weights among programmed vs. natural cycle frozen ETs. There were no differences in the LBR between living or deceased donor uteri (37% vs. 32%). CONCLUSIONS: Posttransplant ovarian stimulation was required in 26% (n = 6/23) of recipients undergoing at least one ET, despite high rates of preimplantation genetic testing and pretransplant embryo cryopreservation. Posttransplant retrievals were performed transvaginally, without complications. Future reporting of IVF treatment experiences will be essential to optimizing reproductive outcomes after a uterus transplant. CLINICAL TRIAL REGISTRATION NUMBERS: NCT02656550 (Baylor University Medical Center); NCT03307356 (University of Pennsylvania); and NCT02573415 (Cleveland Clinic).

Anatomic nomenclature and 3-dimensional regional model of the human ovary: call for a new paradigm.

The ovaries are the female gonads that are crucial for reproduction, steroid production, and overall health. Historically, the ovary was broadly divided into regions defined as the cortex, medulla, and hilum. This current nomenclature lacks specificity and fails to consider the significant anatomic variations in the ovary. Recent technological advances in imaging modalities and high-resolution omic analyses have brought about the need for revision of the existing definitions, which will facilitate the integration of generated data and enable the characterization of organ subanatomy and function at the cellular level. The creation of these high-resolution multimodal maps of the ovary will enhance collaboration and communication among disciplines and between clinicians and researchers. Beginning in March 2021, the Pediatric and Adolescent Gynecology Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development invited subject-matter experts to participate in a series of workshops and meetings to standardize ovarian nomenclature and define the organ's features. The goal was to develop a spatially defined and semantically consistent terminology of the ovary to support collaborative, team science-based endeavors aimed at generating reference atlases of the human ovary. The group recommended a standardized, 3-dimensional description of the ovary and an ontological approach to the subanatomy of the ovary and definition of follicles. This new greater precision in nomenclature and mapping will better reflect the ovary's heterogeneous composition and function, support the standardization of tissue collection, facilitate functional analyses, and enable clinical and research collaborations. The conceptualization process and outcomes of the effort, which spanned the better part of 2021 and early 2022, are introduced in this article. The institute and the workshop participants encourage researchers and clinicians to adopt the new systems in their everyday work to advance the overarching goal of improving human reproductive health.

A multi-institutional study of renal outcomes and renal-related pregnancy outcomes in uterus transplant recipients.

Uterus transplantation (UTx) is an effective treatment option for uterine factor infertility. However, the need for immunosuppression and congenital renal anomalies that coexist with uterine agenesis in about 30% of women with Mayer-Rokitansky-Kuster-Hauser syndrome create a risk for renal dysfunction. We therefore examined renal function trajectory and related pregnancy complications in an international cohort of 18 UTx recipients from September 2016-February 2020 who had at least one live birth. All UTx recipients had a diminution in their renal function that was apparent starting at 30 days posttransplant and in half the reduction in eGFR was at least 20%; the decrease in eGFR persisted into the early post-partum period. Half met criteria for Stage 1 acute kidney injury (AKI) as defined by the AKI Network criteria during their pregnancy. Overall, 28% of UTx recipients developed pre-eclampsia. eGFR was lower at embryo transfer and throughout pregnancy among those who developed pre-eclampsia, reaching statistical significance at week 16 of pregnancy. This effect was independent of tacrolimus levels. Mean eGFR remained significantly lower in the first 1-3 months after delivery. In the subgroup who reached 12 months of postpartum follow up and had a graft hysterectomy (n = 4), there was no longer a statistical difference in eGFR (pretransplant 106.7 ml/m ± 17.7 vs. 12 mos postpartum 92.6 ml/m ± 21.7, p = .13) but the number was small. Further study is required to delineate long term renal risks for UTx recipients, improve patient selection, and make decisions regarding a second pregnancy.

Reproductive Technology Considerations in Uterus Transplant.

Uterus transplantation (UTx) provides a new pathway to parenthood for patients with absolute uterine factor infertility. The application of reproductive technologies, such as in vitro fertilization, embryo cryopreservation, and frozen embryo transfers, for this unique population, is particularly nuanced and continually evolving. There are important pretransplant and posttransplant reproductive considerations for physicians and patients anticipating UTx. As with any rapidly evolving medical innovation, efforts to consolidate experiences and knowledge by centers offering UTx is paramount.

GnRH agonist with low-dose hCG (dual trigger) is associated with higher risk of severe ovarian hyperstimulation syndrome compared to GnRH agonist alone.

PURPOSE: The purpose of this study was to compare rates of ovarian hyperstimulation syndrome (OHSS) after using gonadotropin-releasing hormone agonists (GnRHa) alone and GnRHa in combination with low-dose human chorionic gonadotropin (hCG, dual trigger) for final oocyte maturation in women undergoing controlled ovarian hyperstimulation (COH). METHODS: A retrospective cohort study was conducted at an academic center. Study population included 108 women who received GnRHa trigger and 66 women who received dual trigger (GnRHa + low-dose [1000 IU] hCG trigger). The main outcome measure was OHSS. Secondary outcomes included total oocyte yield and oocyte maturity. RESULTS: The incidence of early OHSS was significantly higher after dual trigger than GnRHa trigger (8.6 vs 0 %). Moreover, four of the six patients that developed OHSS developed severe OHSS. Logistic modeling revealed that the combination of age, BMI, baseline AFC, and E2 >4000 pg/mL was predictive of OHSS with an area under the receiver operating characteristic curve of 0.84 and was superior to each factor alone. Adjusted analyses revealed that dual trigger was associated with a higher number of total oocytes (adjusted OR 1.27; 95 % confidence interval, 1.18, 1.38) and percentage of mature oocytes (AOR 1.10; 95 % confidence interval, 1.03, 1.17) obtained compared to GnRHa trigger alone. CONCLUSIONS: Dual trigger for final oocyte maturation using GnRHa and low-dose hCG is associated with a significantly increased risk of severe OHSS compared to GnRH alone. However, dual trigger may be associated with a modest increase in oocyte yield, both in terms of number and maturity.

Use of gonadotropin-releasing hormone agonist trigger during in vitro fertilization is associated with similar endocrine profiles and oocyte measures in women with and without polycystic ovary syndrome.

OBJECTIVE: To compare endocrine profiles and IVF outcomes after using GnRH agonists (GnRHa) to trigger final oocyte maturation in women with polycystic ovary syndrome (PCOS) with other hyper-responders. DESIGN: Retrospective cohort study. SETTING: Academic center. PATIENT(S): Forty women with PCOS and 74 hyper-responders without PCOS. INTERVENTION(S): GnRHa trigger. MAIN OUTCOME MEASURE(S): Number of oocytes. RESULT(S): Serum E2, LH, and P levels on the day of GnRHa trigger and the day after trigger did not differ significantly between groups. There were no significant differences in total number of oocytes or percent mature oocytes obtained between groups after controlling for age, antral follicle count, and total days of stimulation. The overall rate of no retrieval of oocytes after trigger was low (2.6%). Fertilization, implantation, clinical pregnancy, and live-birth rates were similar in the two groups. No patients developed ovarian hyperstimulation syndrome (OHSS). CONCLUSION(S): The similar post-GnRHa trigger hormone profiles and mature oocyte yield support the routine use of GnRHa trigger to prevent OHSS in women with PCOS.

Sex-related growth differences are present but not enhanced in in vitro fertilization pregnancies.

OBJECTIVE: To determine whether IVF modifies the effect of fetal sex on growth. DESIGN: Retrospective cohort study. SETTING: Tertiary care center and related facilities. PATIENT(S): Singleton live births without fetal/maternal comorbidities from fertile women who conceived without the use of assisted reproductive technologies and infertile women who conceived with IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was birth weight (BW). Secondary outcomes were fetal crown-rump length (CRL) in the first trimester, biparietal diameter (BPD), and estimated fetal weight (EFW) in the second trimester. RESULT(S): There were no differences in baseline characteristics between women carrying male fetuses and those carrying female fetuses in either mode of conception. In unadjusted analyses, the male-female differentials in fetal BPD and BW were more pronounced in the IVF cohort than in the unassisted cohort. In multivariable regression analysis, male BPD exceeded female BPD by 0.12 cm, male EFW exceeded female EFW by 12 g, and male BW exceeded female BW by 172 g. IVF did not have a significant effect on BPD but was associated with a 52 g increase in EFW in the midgestation. IVF was associated with an 81-g reduction in BW. IVF did not modify the magnitude of size differences between the sexes in the midgestation or at birth. CONCLUSION(S): Comparable sex-dependent differential growth occurs in unassisted and IVF pregnancies.

Smaller fetal size in singletons after infertility therapies: the influence of technology and the underlying infertility.

OBJECTIVE: To determine whether fetal size differences exist between matched fertile and infertile women and among women with infertility achieving pregnancy through various treatment modalities. DESIGN: Retrospective cohort study with propensity score analysis. SETTING: Tertiary care center and affiliated community hospitals. PATIENT(S): 1,246 fertile and 461 infertile healthy women with singleton livebirths over a 10-year period. INTERVENTION(S): Infertile women conceiving without medical assistance, with ovulation induction, or with in vitro fertilization. MAIN OUTCOME MEASURE(S): Birthweight; secondary outcomes included crown-rump length, second-trimester estimated fetal weight, and incidence of low birth weight and preterm delivery. RESULT(S): Compared with matched fertile women, infertile women had smaller neonates at birth (3,375 ± 21 vs. 3,231 ± 21 g) and more low-birth-weight infants (relative risk = 1.68, 95% confidence interval, 1.06, 2.67). Neonates conceived via ovulation induction were the smallest among the infertility subgroups compared with the neonates of fertile women (3,092 ± 46 vs. 3,397 ± 44 g). First-trimester fetal size was smaller in infertile versus fertile women (crown-rump length 7.9 ± 0.1 vs. 8.5 ± 0.1 mm). Within the infertility subgroups, no differences in fetal or neonatal size were found. CONCLUSION(S): The inherent pathologic processes associated with infertility may have a larger impact on fetal growth than infertility therapies.

The approach to ovarian dermoids in adolescents and young women.

BACKGROUND: Mature cystic teratomas (MCTs) are the most common ovarian neoplastic lesions found in adolescents. MCTs are usually asymptomatic and are often discovered incidentally on exam or imaging. The recurrence rate of MCTs following cystectomy is 3-4% and incidence of malignant transformation is estimated to be 0.17-2%. Given the accuracy with which MCTs can be diagnosed preoperatively studies suggest that these lesions can be treated surgically using laparoscopic techniques. The management of MCTs in the adolescent population poses unique challenges given the potential impact on sexual development and fertility. CASE: A 17-year-old female was found to have bilateral adnexal masses consistent in appearance with MCTs on computed tomography after a motor vehicle accident. She underwent exploratory laparotomy with pathology confirming the presence of bilateral ovarian MCTs. Three years later she returned to the office with occasional abdominopelvic pain. Ultrasound revealed bilateral complex cysts suggestive of recurrent MCTs. She was expectantly managed with serial ultrasounds and after 24 months, slow but visible growth of the MCTs was confirmed. The patient is now 22 years old and asymptomatic. What is the most appropriate management? SUMMARY AND CONCLUSION: The risks of expectant management in women like the one presented are small. This suggests that although the traditional treatment for MCTs is laparoscopic ovarian cystectomy, in children and adolescents with MCTs we should consider close follow-up without intervention to preserve ovarian function and future fertility.