Association of In Vitro Fertilization With Childhood Cancer in the United States.

Importance: In vitro fertilization (IVF) is associated with birth defects and imprinting disorders. Because these conditions are associated with an increased risk of childhood cancer, many of which originate in utero, descriptions of cancers among children conceived via IVF are imperative. Objective: To compare the incidence of childhood cancers among children conceived in vitro with those conceived naturally. Design, Setting, and Participants: A retrospective, population-based cohort study linking cycles reported to the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System from January 1, 2004, to December 31, 2012, that resulted in live births from September 1, 2004, to December 31, 2013, to the birth and cancer registries of 14 states, comprising 66% of United States births and 75% of IVF-conceived births, with follow-up from September 1, 2004, to December 31, 2014. The study included 275 686 children conceived via IVF and a cohort of 2 266 847 children, in which 10 births were randomly selected for each IVF birth. Statistical analysis was performed from April 1, 2017, to October 1, 2018. Exposure: In vitro fertilization. Main Outcomes and Measures: Cancer diagnosed in the first decade of life. Results: A total of 321 cancers were detected among the children conceived via IVF (49.1% girls and 50.9% boys; mean [SD] age, 4.6 [2.5] years for singleton births and 5.9 [2.4] years for multiple births), and a total of 2042 cancers were detected among the children not conceived via IVF (49.2% girls and 50.8% boys; mean [SD] age, 6.1 [2.6] years for singleton births and 4.7 [2.6] years for multiple births). The overall cancer rate (per 1 000 000 person-years) was 251.9 for the IVF group and 192.7 for the non-IVF group (hazard ratio, 1.17; 95% CI, 1.00-1.36). The rate of hepatic tumors was higher among the IVF group than the non-IVF group (hepatic tumor rate: 18.1 vs 5.7; hazard ratio, 2.46; 95% CI, 1.29-4.70); the rates of other cancers did not differ between the 2 groups. There were no associations with specific IVF treatment modalities or indication for IVF. Conclusions and Relevance: This study found a small association of IVF with overall cancers of early childhood, but it did observe an increased rate of embryonal cancers, particularly hepatic tumors, that could not be attributed to IVF rather than to underlying infertility. Continued follow-up for cancer occurrence among children conceived via IVF is warranted.

Management of congenital uterine abnormalities.

Congenital uterine abnormalities are a heterogeneous group of uterine configurations that may adversely affect reproductive potential. Although subtle variations can occur, the more common abnormalities fall into two broad categories of unilateral development or failure of midline fusion. These abnormalities have been well described for over a century although the mechanisms of their unfavourable impact on fertility and clinical management have not been systematically studied until recently. The quality of the literature on this topic has traditionally fallen below the level on which solid evidence-based decisions can be made. Nonetheless, considerable progress has been made in recent times. The understanding of the aetiology of these abnormalities and how they impact reproduction has matured and evolved and this evolution and the growing body of recent studies better define clinical scenarios in which intervention will clearly and positively impact outcome. This article will review four common congenital abnormalities, their impact on reproduction, options for management and the role of assisted reproduction treatment in maximizing reproductive potential. Recommendations are made with consideration of the quality of the literature in an outcome-driven environment.

Assessment of ovarian reserve by using the follicle-stimulating hormone isoform distribution pattern to predict the outcome of in vitro fertilization.

Changes in FSH isoforms occur at temporally specific times during the menstrual cycle and reproductive lifespan. Changes in ratio in FSH isoforms may provide a sensitive test of ovarian reserve before IVF.

Three-dimensional ultrasound-guided embryo transfer: a preliminary study.

OBJECTIVE: Embryo transfer techniques have emerged as 1 of the most important variables during in vitro fertilization. Two-dimensional ultrasound guidance is an integral part of this procedure and a method to monitor catheter passage through the cervix into the endometrial cavity. Catheter placement may better be achieved with 3-dimensional monitoring to assess the relationship of the catheter tip to the uterine cavity. The purpose of this study was to compare the precision of catheter placement and position by 2- and 3-dimensional ultrasound. STUDY DESIGN: Twenty-four patients were studied. The cervix, uterus, and endometrial cavity were prescreened in 2 dimensions at the midline in the longitudinal plane of the uterus. Embryo transfers were then performed under 2-dimensional guidance. After satisfactory catheter placement and transfer of the embryos, the catheter was held in place for 60 to 120 seconds. During this interval, an automated, single sweep of the uterus and endometrial cavity was performed for net volume acquisition. All images were stored and retrospectively reviewed. Embryo transfer catheter placement with 2-dimensional ultrasound guidance was then compared with the images obtained in 3 simultaneous planes. RESULTS: Visualization of the embryo catheter tip with 2-dimensional ultrasound was achieved in all patients. These images suggested that the catheter was 2 cm from the uterine fundus and in the midline. Satisfactory 3-dimensional images for review and comparison were obtained in 21 of 24 patients. Three-dimensional ultrasound images confirmed placement and agreed with findings of 2-dimensional ultrasound images in 17 of 21 patients. In 4 patients, the catheter tip on 3-dimensional ultrasound was observed to be displaced either anteriorly or laterally from the ideal region as suggested by 2-dimensional ultrasound. In 1 case, the catheter tip on 3-dimensional ultrasound was observed to be far laterally in the region of the uterine cornua. CONCLUSION: Two-dimensional ultrasound-guided embryo transfer continues to be the standard for image-guided transfers. Data of the present study suggest that the precision of catheter tip placement and consequently embryo transfer may be improved with 3-dimensional imaging. Four of 21 patients studied had catheter tip placement in a different and less-than-ideal area when studied with 3-dimensional ultrasound. Three-dimensional imaging may provide an improvement in embryo transfer technique and have a positive impact on overall pregnancy rates.

Anovulation in the prevention of cytotoxic-induced follicular attrition and ovarian failure.

BACKGROUND: Gonadal failure secondary to alkylating agents may be related to ovulatory status. The objective of this investigation was to evaluate whether anovulation protected ovarian follicles during treatment with cyclophosphamide. METHODS: Four groups (n = 20 mature female Sprague-Dawley rats per group) were studied: control (group I), 5 mg/kg/day cyclophosphamide only (group II), 5 mg/kg/day cyclophosphamide and the combination of 50 micro g ethinyl estradiol/2 mg norgestrel (group III) and 5 mg/kg/day cyclophosphamide and 2.5 micro g leuprolide acetate daily (group IV). Animals were sacrificed after 4 weeks of treatment. Follicles were classified as medium (300-450 micro m) and large (>450 micro m) per section of ovary. RESULTS: Group II developed a significantly greater number of medium and large follicles [15.1 +/- 6.1 and 4.9 +/- 1.9 (mean +/- SD), respectively] compared with group I [7.1 +/- 2.1 and 1.0 +/- 0.7 (mean +/- SD), respectively] (P

Medical education as a science: the quality of evidence for computer-assisted instruction.

OBJECTIVE: A marked increase in the number of computer programs for computer-assisted instruction in the medical sciences has occurred over the past 10 years. The quality of both the programs and the literature that describe these programs has varied considerably. The purposes of this study were to evaluate the published literature that described computer-assisted instruction in medical education and to assess the quality of evidence for its implementation, with particular emphasis on obstetrics and gynecology. STUDY DESIGN: Reports published between 1988 and 2000 on computer-assisted instruction in medical education were identified through a search of MEDLINE and Educational Resource Identification Center and a review of the bibliographies of the articles that were identified. Studies were selected if they included a description of computer-assisted instruction in medical education, regardless of the type of computer program. Data were extracted with a content analysis of 210 reports. The reports were categorized according to study design (comparative, prospective, descriptive, review, or editorial), type of computer-assisted instruction, medical specialty, and measures of effectiveness. RESULTS: Computer-assisted instruction programs included online technologies, CD-ROMs, video laser disks, multimedia work stations, virtual reality, and simulation testing. Studies were identified in all medical specialties, with a preponderance in internal medicine, general surgery, radiology, obstetrics and gynecology, pediatrics, and pathology. Ninety-six percent of the articles described a favorable impact of computer-assisted instruction in medical education, regardless of the quality of the evidence. Of the 210 reports that were identified, 60% were noncomparative, descriptive reports of new techniques in computer-assisted instruction, and 15% and 14% were reviews and editorials, respectively, of existing technology. Eleven percent of studies were comparative and included some form of assessment of the effectiveness of the computer program. These assessments included pre- and posttesting and questionnaires to score program quality, perceptions of the medical students and/or residents regarding the program, and impact on learning. In one half of these comparative studies, computer-assisted instruction was compared with traditional modes of teaching, such as text and lectures. Six studies compared performance before and after the computer-assisted instruction. Improvements were shown in 5 of the studies. In the remainder of the studies, computer-assisted instruction appeared to result in similar test performance. Despite study design or outcome, most articles described enthusiastic endorsement of the programs by the participants, including medical students, residents, and practicing physicians. Only 1 study included cost analysis. Thirteen of the articles were in obstetrics and gynecology. CONCLUSION: Computer-assisted instruction has assumed to have an increasing role in medical education. In spite of enthusiastic endorsement and continued improvements in software, few studies of good design clearly demonstrate improvement in medical education over traditional modalities. There are no comparative studies in obstetrics and gynecology that demonstrate a clear-cut advantage. Future studies of computer-assisted instruction that include comparisons and cost assessments to gauge their effectiveness over traditional methods may better define their precise role.

A 7.5-MHz finger-grip ultrasound probe for real-time intraoperative guidance during complex reproductive surgical procedures.

OBJECTIVE: A 7.5-MHz finger-grip probe was used to monitor intra-abdominal reproductive surgery in two groups of patients. STUDY DESIGN: The first group of patients underwent transabdominal myomectomy for multiple uterine leiomyomas (n = 3) and the second group underwent uterine reconstruction and excision of obstructive uterine horn (n = 3). Intraoperative real-time imaging was accomplished by direct application of the finger-grip probe to the uterine serosa by using saline solution as a transmission media. Ultrasound imaging and surgical dissection were carried out both sequentially and simultaneously. RESULTS: In the first group of patients, the finger-grip probe provided precise location of the leiomyomas and intraoperative guidance for dissection during the myomectomy. In the second group of patients, the finger probe provided images of intrauterine anatomy in one patient who had a normal-sized and normal-shaped uterus with an obstructed intracavitary horn and hematometrium. In two other patients, the obstructed uterine horn extended deep into the pelvis lateral to the vagina. Real-time imaging provided intraoperative monitoring of depth of dissection into the paravaginal space. CONCLUSION: The finger-grip probe demonstrated intrauterine anatomy and enabled a more directed surgical approach, both in placement of uterine incisions for surgical reconstruction and excision of obstructed horns for mullerian abnormalities and in identification and dissection for leiomyomas.

How virtual reality may enhance training in obstetrics and gynecology.

OBJECTIVE: Contemporary training in obstetrics and gynecology is aimed at the acquisition of a complex set of skills oriented to both the technical and personal aspects of patient care. The ability to create clinical simulations through virtual reality (VR) may facilitate the accomplishment of these goals. The purpose of this paper is 2-fold: (1) to review the circumstances and equipment in industry, science, and education in which VR has been successfully applied, and (2) to explore the possible role of VR for training in obstetrics and gynecology and to suggest innovative and unique approaches to enhancing this training. MATERIAL AND METHODS: Qualitative assessment of the literature describing successful applications of VR in industry, law enforcement, military, and medicine from 1995 to 2000. Articles were identified through a computer-based search using Medline, Current Contents, and cross referencing bibliographies of articles identified through the search. RESULTS: One hundred and fifty-four articles were reviewed. This review of contemporary literature suggests that VR has been successfully used to simulate person-to-person interactions for training in psychiatry and the social sciences in a variety of circumstances by using real-time simulations of personal interactions, and to launch 3-dimensional trainers for surgical simulation. These successful applications and simulations suggest that this technology may be helpful and should be evaluated as an educational modality in obstetrics and gynecology in two areas: (1) counseling in circumstances ranging from routine preoperative informed consent to intervention in more acute circumstances such as domestic violence or rape, and (2) training in basic and advanced surgical skills for both medical students and residents. CONCLUSION: Virtual reality is an untested, but potentially useful, modality for training in obstetrics and gynecology. On the basis of successful applications in other nonmedical and medical areas, VR may have a role in teaching essential elements of counseling and surgical skill acquisition.