Perinatal Outcome of Singletons Born after Using a Simplified Low-Cost IVF Culture System and All Singletons Born in Flanders (Belgium) between 2012 and 2020.

BACKGROUND: We developed a simplified IVF culture system (SCS) which has proven to be effective and safe in a selected IVF cohort. METHODS: Preterm birth (PTB) and low birth weight (LBW) of 175 singletons born after using the SCS, 104 after fresh embryo transfer (ET), and 71 after frozen embryo transfer, were compared with all singletons born in Flanders between 2012 and 2020 conceived after natural conception, ovarian stimulation (OS), and assisted reproduction (IVF/ICSI). FINDINGS: The proportion of preterm (<37 weeks) births was significantly higher in the case of IVF or ICSI, followed by hormonal treatment, compared to spontaneous pregnancies. There was no significant difference in PTB between SCS and any of the other groups. Concerning the average birth weight we found no significant difference between singletons born after natural conception and SCS. However, a significant difference in average birth weight was found between SCS singletons and singletons born after IVF, ICSI and hormonal treatment, with a significantly higher birth weight in the SCS group. This difference was also observed in the proportion of babies weighing less than 2500 g, with significantly more LBW babies in the IVF and ICSI group compared to the SCS newborns. INTERPRETATION: Taking into account the small series, PTB and LBW rates in SCS singletons were found to be comparable with singletons born after natural conception. Compared to babies born after ovarian stimulation and IVF/ICSI, SCS singletons had a lower PTB and LBW rates, although the differences were not significant for PTB. Our results confirm previous reports on reassuring perinatal outcomes after using the SCS technology.

Promising Perinatal Outcome after Using a Simplified Low-Cost IVF Culture System Specifically Designed for Resource-Poor Countries.

BACKGROUND: Assisted reproductive techniques services are often not accessible to the majority of infertile couples in Low and Middle Income Countries (LMIC) due to high costs. Lowering IVF laboratory costs is a crucial step to make IVF affordable for a larger part of the world population. We developed a simplified culture system (SCS) which has proven to be effective, and the next step is to prove its safety. METHODS: Preterm birth (PTB) and low birthweight (LBW) of 176 singletons born after using the SCS, 105 after fresh embryo transfer (fresh ET), and 71 after frozen embryo transfer (frozen ET) were compared with all IVF/ICSI singletons born in Belgium between 2013 and 2018. When comparing our 105 SCS babies born after fresh ET with all Belgian babies born after conventional IVF only, we also adjusted for 7 risk factors known to influence perinatal outcome, namelythe mother's age, day of transfer, pituitary inhibition protocol, rank of cycles, number of oocytes retrieved, number of embryos transferred, and gender of the baby. FINDINGS: Before adjustment, we found a significantly higher PTB (10.2% vs. 3.8%, OR 2.852, 95% CI [1.042-7.803], p-value 0.0413) and LBW (9.8% vs. 2.9%, OR 3.692, 95% CI [1.163-11.721], p-value 0.0267) in the conventional IVF group versus SCS after fresh ET. After adjusting for seven risk parameters, these differences remained significant (PTB: OR 2.627, 95% CI [1.013-6.816], p-value 0.0471) and LBW: OR 3.267, 95% CI [1.118-9.549], p-value 0.0305). PTB and LBW between both groups was not significantly different for singletons born after frozen ET. INTERPRETATION: Taking into account the small series, PTB and LBW rates in SCS singletons in FRET cycles are very reassuring and significantly lower compared to babies born after conventional IVF in Belgium. Being aware of its effectiveness, our results offer a good perspective for SCS to become an important tool to implement low-cost IVF in LMIC.

Multiyear outcomes using sibling oocytes demonstrates safety and efficacy of a simplified culture system consistent with use in a low-cost IVF setting.

RESEARCH QUESTION: Can a novel closed simplified IVF culture system be used to achieve outcomes comparable to those obtained with intracytoplasmic sperm injection (ICSI) followed by conventional culturing? DESIGN: This analysis is part of a non-inferiority prospective study comparing ICSI and a simplified culture system (SCS) for gamete fertilization in a selected group of patients. According to protocol, sibling oocytes in intact cumulus-oocyte complexes were randomly distributed between ICSI and conventional insemination in the SCS. For women, selection criteria included being under 43 years of age and at least six eggs at retrieval. An inseminating motile sperm count ≥1 million was required. The primary outcome measure was ongoing pregnancy rate (>12 weeks) per cycle; secondary outcome measures included fertilization rate, miscarriage rate and implantation rate (ongoing pregnancy rate per embryo). RESULTS: From January 2016 until December 2019, 653 SCS/ICSI cycles were performed yielding a total of 7915 oocytes. The fertilization rate was 61.1% and 50.4% for SCS and ICSI (P < 0.0001), respectively. The ongoing pregnancy rate was 32.0% for SCS and 36.7% for ICSI (P = 0.27). Implantation rate was 30.6% for SCS and 34.4% for ICSI (P = 0.35). The miscarriage rate was 7.5% and 6.5% for SCS and ICSI, respectively (P = 0.75). CONCLUSION: No difference was found in ongoing pregnancy rate, implantation rate and the miscarriage rate between SCS and ICSI in this selected patient cohort.

Perinatal outcome of babies born after using a simplified IVF culture system versus ICSI with sibling oocytes: a prospective cohort study.

RESEARCH QUESTION: Is there a difference in perinatal outcome in the same patient cohort for babies conceived following randomization of sibling oocytes allocated to a simplified IVF culture system (SCS) or intracytoplasmic sperm injection (ICSI) followed by conventional culturing? DESIGN: The study compared the perinatal outcomes of 367 babies born from 1 January 2013 until 31 December 2020 after using split SCS and ICSI insemination of sibling oocytes in a selected group of normo-responsive women, excluding cases of severe male infertility. Primary outcome measures were preterm birth (PTB; <37 weeks' gestation), low birthweight (LBW; <2.5 kg) and small for gestational age (SGA) as a primary outcome parameter while secondary outcome measures included mean birthweight, mean gestational age, extreme prematurity (<32 weeks), very low birthweight (<1.5 kg), perinatal mortality, multiple pregnancy and Caesarean section rate. RESULTS: A total of 105 and 103 singleton babies were born after fresh embryo transfer (FRET) and 71 and 50 singletons after frozen embryo transfer (FET) in the SCS and ICSI groups, respectively. For babies born after FRET, the LBW rate was 2.9% (3/105) for SCS and 7.8% (8/103) for ICSI (P = 0.10). LBW occurred in 4.2% (3/71) and 0% (0/50) of babies born after the transfer of cryopreserved-thawed SCS and ICSI embryos, respectively (P = 0.14). The rate of PTB was 3.8% and 6.8% for SCS and ICSI in FRET cycles (P = 0.33), and 8.5% and 6.0% for SCS and ICSI in FET cycles (P = 0.62). One congenital malformation was found in the SCS FET group. CONCLUSION: There was no difference in perinatal outcome for singleton and twin babies born after SCS and ICSI.

International Consensus Statement for Recommended Terminology Describing Hysteroscopic Procedures.

OBJECTIVE: To develop a consensus statement of recommended terminology to use for describing different aspects of hysteroscopic procedures that can be uniformly used in clinical practice and research. DESIGN: Open forum discussion followed by online video meetings. SETTING: International community of hysteroscopy experts PATIENTS: Not applicable. INTERVENTIONS: Series of online video meetings to complete a previously established agenda until a final agreement for standardized nomenclature was obtained. MEASUREMENT AND MAIN RESULTS: The adoption and implementation of a common terminology to standardize reporting of hysteroscopic procedures was proposed to cover five domains: pain management, healthcare setting, model of care, type of hysteroscopic procedure and the hysteroscopic approach to the uterine cavity. A final agreement was obtained after 3 online video meetings. CONCLUSION: Hysteroscopy is the gold standard technique for the evaluation and management of uterine disorders. A clear definition and understanding of the terminology used to describe hysteroscopic procedures is lacking. The production of this international consensus statement for terminology to describe hysteroscopic procedures, covering pain management, setting, model of care, type of procedure and hysteroscopic approach, has the potential to enable more effective communication for both clinical and research purposes with the ultimate aim of improving patient care and clinical outcomes.

Long-Term Reproductive Outcomes after Hysteroscopic Treatment of Dysmorphic Uteri in Women with Reproductive Failure: An European Multicenter Study.

OBJECTIVE: To evaluate the long-term reproductive outcomes in patients with dysmorphic uterus treated by hysteroscopic metroplasty with miniaturized instruments. DESIGN: Retrospective multicenter cohort study. SETTING: Tertiary care university hospitals. PATIENTS: The study was conducted on 214 women with a dysmorphic uterus (T-shaped, infantilis, or other type of dysmorphic uterus according to the European Society of Human Reproduction and Embryology and the European Society for Gynaecological Endoscopy classification system) with history of primary unexplained infertility (group 1) or repeated (>2) early miscarriages (group 2). Dysmorphic uteri were diagnosed by office hysteroscopy and 3-dimensional transvaginal ultrasound (3D-TVS). INTERVENTIONS: All patients underwent in office hysteroscopic metroplasty using a continuous-flow hysteroscope with a 5 Fr operating channel introduced into the uterine cavity using the vaginoscopic approach. Longitudinal incisions were performed on the fibromuscular constriction rings in the isthmic area and in some cases on the other uterine walls with a 5 Fr bipolar electrode or scissors. At the end of the procedure, an antiadhesive gel was applied into the uterine cavity to minimize adhesion formation. Postsurgical assessment of the uterine cavity was carried out through office hysteroscopy and 3D-TVS. All patients were followed for at least 24 months. MEASUREMENTS AND MAIN RESULTS: The metroplasty was completed in all cases, resulting in a significant increase of uterine cavity volume (100%) and optimization of uterine morphology in 211 of 214 women (98.6%). After 60 months, the overall clinical pregnancy rate was 72.9% (n = 156/214), and the live birth rate was 80.1% (n = 125/156). Specifically, 74 of 156 women (47.4%) conceived spontaneously (with a median time to pregnancy of 5.5 months), of whom 32.4% had previously failed 1 or more attempts at in vitro fertilization/intracytoplasmic sperm injection. CONCLUSION: Our long-term follow-up data demonstrate that the hysteroscopic correction of dysmorphic uteri may result in a high live birth rate in women suffering from unexplained infertility or repeated miscarriages.

Resectoscopic Metroplasty with Uterine Septum Excision: A Histologic Analysis of the Uterine Septum.

STUDY OBJECTIVE: To evaluate the histology of the uterine septum after its complete hysteroscopic excision. DESIGN: Case series. SETTING: Second Gynecological and Obstetric Unit and Pathological Anatomy Department of the University of Bari, Italy. PATIENTS: Thirty-five patients aged between 25 and 41 years who were diagnosed with uterine septum by 3-dimensional ultrasound per the European Society for Human Reproduction and Embryology/European Society of Gastrointestinal Endoscopy 2013/Salim 2003 criteria. In addition, office hysteroscopy was performed to define the anatomy of the uterine cavity and to exclude the presence of other endometrial pathologic conditions. INTERVENTIONS: Operative hysteroscopic septum resection was performed. The septum was initially incised with an "L-shape" bipolar electrode with a 5-mm bipolar mini-resectoscope (KARL STORZ SE & Co. KG, Tuttlingen, Germany). Then, using the bipolar loop, 2 triangles of the septum were excised in parallel, obtaining uninterrupted entire septum-long strips from the fundus to the apex of the septum. These strips were immediately removed from the uterus and reassembled in vitro to reconstruct a macroscopic, 3-dimensional structure of the septum for complete morphologic and histologic evaluations. MEASUREMENTS AND MAIN RESULTS: Patients presented with an average body mass index of 24.8 kg/m2and were all nulliparous. Histologic evaluation of the uterine septa showed a different conformation of the muscle bundles along the septum. Muscle cells in the apex and edges of the septum were arranged in nodules circumscribed by a thin area of collagen fibers. Medium-sized vessels were distributed in the collagen fibers around the muscle cells. Only few capillary vessels were present in the muscle nodules. This pattern was very similar to the cell arrangement in leiomyomas. In the core of the septa, near the base, the muscle bundles showed a linear course with concurrent collagen fibers and vessels. All the aforementioned characteristics were consistently present in every patient. On high-power histologic fields (200×), the muscle portion accounted for 48.3% ± 1.8% (mean, 6%) area in the apex and borders to 48.5% ± 1.3% (mean, 6%) area in the core. Collagen fibers accounted for 27.1% ± 1.1% (mean, 4%) area in the apex and borders to 26.7% ± 1.3% (mean 5%) area in the core. CONCLUSION: By removing the septum as a whole structure, this study allowed us to redefine the concept of the septum as a complex structure according to the islands of muscle fibers irregularly arranged in vertex, in a context of collagen tissue and similar to the structure of myomas. It appears to deeply involve the anterior and posterior uterine walls, resembling a "reverse letter H."

Training and qualification in gynecological minimal access surgery: A systematic review.

Minimally invasive surgery demands specific endoscopic psychomotor skills that are usually acquired outside the operating theatre. We present the results of a systematic analysis to identify how simulation is used during training and qualification in minimal access surgery to improve gynecologist's surgical skills. We found that despite the availability of simulation tools along with methods for training and testing specific endoscopic psychomotor and technical skills, there is no clear evidence of the superiority of one tool or method over the others in skill acquisition. However, prospective studies show that well-guided training courses combined with different trainers and methods improve significantly surgeon's laparoscopic skills and suturing ability, which are unforgettable over time. However, this proficiency could deteriorate over time when it is solely learned and executed on simulation trainers. Structured curricula including theory, simulation, and live-surgery seem to be the best option for trainees. More research in this field is needed.

Symptoms and classification of uterine adenomyosis, including the place of hysteroscopy in diagnosis.

Where histology used the presence of glands and/or stroma in the myometrium as pathognomonic for adenomyosis, imaging uses the appearance of the myometrium, the presence of striations, related to the presence of endometrial tissue within the myometrium, the presence of intramyometrial cystic structures and the size and asymmetry of the uterus to identify adenomyosis. Preliminary reports show a good correlation between the features detected by imaging and the histological findings. Symptoms associated with adenomyosis are abnormal uterine bleeding, pelvic pain (dysmenorrhea, chronic pelvic pain, dyspareunia), and impaired reproduction. However a high incidence of existing comorbidity like fibroids and endometriosis makes it difficult to attribute a specific pathognomonic symptom to adenomyosis. Heterogeneity in the reported pregnancy rates after assisted reproduction is due to the use of different ovarian stimulation protocols and absence of a correct description of the adenomyotic pathology. Current efforts to classify the disease contributed a lot in elucidated the potential characteristics that a classification system should be relied on. The need for a comprehensive, user friendly, and clear categorization of adenomyosis including the pattern, location, histological variants, and the myometrial zone seems to be an urgent need. With the uterus as a possible unifying link between adenomyosis and endometriosis, exploration of the uterus should not only be restricted to the hysteroscopic exploration of the uterine cavity but in a fusion with ultrasound.

Survey among ESGE members on leiomyosarcoma morcellation incidence.

BACKGROUND: Increased awareness of leiomyosarcoma (LMS) risk during myomectomy or hysterectomy is essential. Objective and correct reasoning should prevail on any decision regarding the extent and type of surgery to employ. The anticipated risk of a sarcoma after myoma or uterus morcellation is low, and the frequency of leiomyosarcoma especially in women below the age of 40 is very rare. The prevalence data has a wide range and is therefore not reliable. The European Society of Gynaecological Endoscopy (ESGE) initiated a survey among its members looking into the frequency of morcellated leiomyosarcoma after endoscopic surgery.The ESGE Central office sent 3422 members a structured electronic questionnaire with multiple answer choices for each question. After 3 months, the answers were classified with a unique number in the EXCEL spread sheet. Statistical analysis was done using the SPSS v.18. RESULTS: Out of 3422 members, 294 (8.6%) gynaecologists replied to the questionnaire; however, only 240 perform myomectomies by laparoscopy and hysteroscopy and hysterectomies by laparoscopy. The reported experience in performing laparoscopic myomectomy, hysteroscopic myomectomy, laparoscopic hysterectomy (LH), and laparoscopic subtotal hysterectomy (LSH) on an average was 10.8 (1-32) years. The vast majority of 67.1% had over 5 years of practice in laparoscopic surgery. The total number of 221 leiomyosarcoma was reported among 429,777 minimally invasive surgeries (laparoscopic and hysteroscopic myomectomies and LH and LSH), performed by all doctors in their lifetime. The overall reported sarcoma risk of all types of endoscopic myoma surgeries has been estimated to be 1.5% of operations which is very rare. Categorizing by type, 57 (0.06%) LMS were operated by laparoscopic myomectomy and 54 (0.07%) by hysteroscopic myomectomy, while 38 (0.13%) leiomyosarcoma operated by laparoscopic subtotal hysterectomy and 72 (0.31%) by laparoscopic hysterectomy. The probability of a sarcoma after morcellation to be falsely diagnosed by histopathology as a benign tumour and later identified as a sarcoma in a later examination has been reported and calculated to be 0.2%. The low risk of a sarcoma is also reflected by the small number of surgeries, where only 32 doctors reported that they operated once, 29 twice, and 18 operated on 3-10 sarcomas by laparoscopy during their lifetime. CONCLUSION: The survey demonstrated that myomectomy by hysteroscopy or laparoscopy has similar risks of sarcoma with an estimated incidence of 0.07%, much lower than that by laparoscopic hysterectomy and subtotal hysterectomy. Hence, for young patients with myoma infertility problem and low risk for LMS, myomectomy by MIS can be the first option of treatment. The fact that only 12.5% (216/1728) of uterine sarcoma cases are operated laparoscopically demonstrates the surgeons' awareness and alertness about LMS and the potential of spreading sarcomatous cells after myoma/uterus power morcellation.

Face and content validity of the virtual reality simulator 'ScanTrainer®'.

BACKGROUND: Ultrasonography is a first-line imaging in the investigation of women's irregular bleeding and other gynaecological pathologies, e.g. ovarian cysts and early pregnancy problems. However, teaching ultrasound, especially transvaginal scanning, remains a challenge for health professionals. New technology such as simulation may potentially facilitate and expedite the process of learning ultrasound. Simulation may prove to be realistic, very close to real patient scanning experience for the sonographer and objectively able to assist the development of basic skills such as image manipulation, hand-eye coordination and examination technique. OBJECTIVE: The aim of this study was to determine the face and content validity of a virtual reality simulator (ScanTrainer®, MedaPhor plc, Cardiff, Wales, UK) as reflective of real transvaginal ultrasound (TVUS) scanning. METHOD: A questionnaire with 14 simulator-related statements was distributed to a number of participants with differing levels of sonography experience in order to determine the level of agreement between the use of the simulator in training and real practice. RESULTS: There were 36 participants: novices (n = 25) and experts (n = 11) who rated the simulator. Median scores of face validity statements between experts and non-experts using a 10-point visual analogue scale (VAS) ratings ranged between 7.5 and 9.0 (p > 0.05) indicated a high level of agreement. Experts' median scores of content validity statements ranged from 8.4 to 9.0. CONCLUSIONS: The findings confirm that the simulator has the feel and look of real-time scanning with high face validity. Similarly, its tutorial structures and learning steps confirm the content validity.

Dominant hand, non-dominant hand, or both? The effect of pre-training in hand-eye coordination upon the learning curve of laparoscopic intra-corporeal knot tying.

BACKGROUND: Training of basic laparoscopic psychomotor skills improves both acquisition and retention of more advanced laparoscopic tasks, such as laparoscopic intra-corporeal knot tying (LICK). This randomized controlled trial (RCT) was performed to evaluate the effect of different pre-training programs in hand-eye coordination (HEC) upon the learning curve of LICK. RESULTS: The study was performed in a private center in Asunción, Paraguay, by 60 residents/specialists in gynaecology with no experience in laparoscopic surgery. Participants were allocated in three groups. In phase 1, a baseline test was performed (T1, three repetitions). In phase 2, participants underwent different training programs for HEC (60 repetitions): G1 with both the dominant hand (DH) and the non-dominant hand (NDH), G2 with the DH only, G3 none. In phase 3, a post HEC/pre LICK training test was performed (T2, three repetitions). In phase 4, participants underwent a standardized training program for LICK (60 repetitions). In phase 5, a final test was performed (T3, three repetitions). The score was based on the time taken for task completion system. The scores were plotted and non-linear regression models were used to fit the learning curves to one- and two-phase exponential decay models for each participant (individual curves) and for each group (group curves). For both HEC and LICK, the group learning curves fitted better to the two-phase exponential decay model. For HEC with the DH, G1 and G2 started from a similar point, but G1 reached a lower plateau at a higher speed. In G1, the DH curve started from a lower point than the NDH curve, but both curves reached a similar plateau at comparable speeds. For LICK, all groups started from a similar point, but immediately after HEC training and before LICK training, G1 scored better than the others. All groups reached a similar plateau but with a different decay, G1 reaching this plateau faster than the others groups. CONCLUSIONS: This study demonstrates that pre-training in HEC with both the DH and the NDH shortens the LICK learning curve.

The management of polyps in female reproductive organs.

Polyps of the lower reproductive tract are found in 7.8-50% of women. It has been hypothesized that cytogenetic modifications on chromosomes 6, 7 and 12 as well as epigenetic factors involving enzyme and metabolic activities may cause polyps to develop. Cervical polyps found in 2-5% of cases are of low clinical significance and can cause, although rarely, post coital bleedings. Cervical polyps grow during pregnancy and mucorrhoea. Trans vaginal ultrasound (TVU) provides an excellent diagnostic technique to diagnose the size and the anatomic location of endometrial polyps (EPs). In asymptomatic young woman with small EPs <10 mm in size, conservative management can be safely followed by monitoring the polyp growth. EPs located at the fundal and tubocornual regions mechanically affect fertility and disturb normal cellular function due to chronic inflammation. In cases where Eps are a cause of subfertility mechanical hysteroscopic resection is advisable. When the sole reason for infertility is an EP, the patient often becomes spontaneously pregnant shortly after removal. EP Detection in either peri- or post-menopausal age, in symptomatic or asymptomatic patients calls for meticulous hysteroscopic examination and polypectomy is mandatory. Endometrial curettage is also recommended to rule out sub clinical endometrial hyperplasia or cancer. Hysteroscopic surgery for large EPs using bipolar resectoscopes, hysteroscopic morcellators or shavers are considered equally efficient and safe under general anaesthesia. Recurrence rate of EPs after resection is unknown. The recent advances in TVU and hysteroscopy, however, should provide an accurate diagnosis and effective treatment of polyp in the female reproductive tract with minimal recurrence or surgery complications. The significantly increased incidence of colorectal polyps in cohorts that also had EPs might indicate that patients with EPs should be also referred for colonoscopy. EPs have the lowest incidence of malignant transformation as compared to colon, urinary bladder, oropharyngeal, nasal and laryngeal carcinomas.