Experiences of nonpregnant couples after receiving reproductive genetic carrier screening results in Belgium.

Reproductive genetic carrier screening (RGCS) allows for the identification of couples who have an increased likelihood of conceiving a child with a particular autosomal recessive or X-linked condition. The aim of this study was to assess the level of satisfaction, anxiety, knowledge retention, psychosocial and counseling-related aspects among couples who chose to have RGCS. Participants were initially informed about their screening results by telephone. After obtaining a written report of test results, participants were asked to complete an individual self-administered questionnaire. All participants (n = 67) felt they had enough information to make an informed choice. None of the participants regretted their choice to have RGCS. Test results were most often shared with parents (61%) or siblings (37%). Our findings demonstrate that the information/counseling and reporting strategy that was used in the context of this study led to high participant satisfaction, an increase in knowledge over time and favorable psychosocial and counseling-related outcomes.

Fertility preservation counselling for women with endometriosis: a European online survey.

BACKGROUND: Endometriosis is a common cause for infertility. Decreased ovarian reserve due to pathology or surgical management can reduce the chances of natural pregnancy and limit the effectiveness of controlled ovarian stimulation during fertility treatment. Cryopreservation of oocytes or ovarian cortex prior to surgery or before loss of follicular capital is a strategy to preserve fecundity. METHODS: An online survey was sent to reproductive specialists and gynecological surgeons representing major centers of reproductive medicine in Europe to investigate current fertility preservation practices for endometriosis patients. RESULTS: Of 58 responses, 45 (77.6%) in 11/13 countries reported the existence of endometriosis management guidelines, of which 37/45 (82.2%) included treatment recommendations for infertile patients. Most centers (51.7%) reserved fertility counselling for severe endometriosis (large endometriomas with or without deep endometriosis) while 15.5% of centers did not offer fertility preservation for endometriosis. CONCLUSIONS: To address non-uniformity in available guidelines and the diversity in fertility preservation practices, we propose an algorithm for managing patients with severe endometriosis most likely to be impacted by reduced ovarian reserve. Improved awareness about the possibilities of fertility preservation and clear communication between gynaecological surgeons and reproductive medicine specialists is mandatory to address the unmet clinical need of preventing infertility in women with endometriosis.

Exploring informed choice in preconception reproductive genetic carrier screening by using a modified Multidimensional Measure of Informed Choice.

OBJECTIVES: To explore informed choice in reproductive genetic carrier screening (RGCS). METHODS: Women visiting a gynaecologist practice in Flanders (Belgium) were asked to consider participation in a study where RGCS was offered for free to them and their male partner. A modified Multidimensional Measure of Informed Choice was used to determine whether couples who opted for RGCS made an informed choice. In addition, we assessed risk perception, feelings towards RGCS, anxiety and decisional conflict. RESULTS: Most participants (82 %, n = 63/77) made an informed choice with regard to RGCS according to our modified MMIC. Thirteen participants made an uninformed choice due to insufficient knowledge and one participant because of insufficient knowledge and value-inconsistency. Anxiety scores were elevated for three participants. Two participants presented with decisional conflict. CONCLUSION: Our results show high rates of informed choice among non-pregnant couples who were offered RGCS in a research study and received up to 30 min of pre-test counseling. PRACTICE IMPLICATIONS: Limited resources outside a research context may impact informed choice. Pre-test counselling initiatives for RGCS should ideally be organized in such a way that information can be provided at multiple time points to avoid information overload and to allow for a reflection period.

Reasons affecting the uptake of reproductive genetic carrier screening among nonpregnant reproductive-aged women in Flanders (Belgium).

Reproductive genetic carrier screening (RGCS) allows to identify couples who have an increased likelihood of conceiving a child affected with an autosomal recessive or X-linked monogenic condition. Multiple studies have reported on a wide and fragmented set of reasons to accept or decline RGCS. Only a few studies have been performed to assess the uptake of RGCS. Nonpregnant women visiting their gynecologist were invited to complete a questionnaire assessing perceived susceptibility, the acceptability of offering RGCS, attitudes, the intention to participate in RGCS, reasons to accept or decline RGCS, and sociodemographic characteristics. Women who showed the intention to have RGCS were asked to consider a free RGCS offer. Most women (n = 127) were between 25 and 34 years old (60%), in a relationship (91%), and wanted to have children (65%). Study participants had positive attitudes towards RGCS and the intention to consider RGCS in the future. Reasons to accept RGCS were being able to share genetic information with children or relatives (n = 104/127, 82%), to prevent the birth of a child affected with a hereditary condition (n = 103/127, 81%), and/or to know the chance of conceiving a child with a hereditary condition (n = 102/127, 80%). Reasons for declining RGCS were the possible concerns that could arise when receiving test results (n = 27/127, 21%), having no family history of hereditary disorders (n = 19/127, 15%), and not wanting to take action based on test results (n = 13/127, 10%). Among test intenders that met the inclusion criteria, 53% decided to participate in RGCS together with their male reproductive partner. More in-depth research on the decision-making process behind the choice to accept or decline an RGCS offer would be highly valuable to make sure couples are making informed reproductive choices.

Effect of mild α-chymotrypsin treatment of highly viscous semen samples on fertilization rates.

BACKGROUND: Highly viscous semen reduces sperm motility significantly and can contribute to infertility. When processing semen samples, few techniques exist to induce liquefaction in case of seminal hyperviscosity such as different washing steps and mechanical treatment. The use of α-chymotrypsin seems controversial due to possible negative effects on fertilisation rates after in vitro fertilization (IVF). The main objective of this study was to examine the influence of mild α-chymotrypsin treatment of semen samples on the fertilisation rate after artificial reproductive treatment (ART). METHODS: The fertilization rate of 52 ART cycles was examined following IVF using a low dose of α-chymotrypsin to induce liquefaction of highly viscous semen and was compared to a control group of 88 ART cycles. RESULTS: There was no significant difference in the fertilization rates of α-chymotrypsin treated semen samples compared to the control group; pregnancy rates were unaffected. CONCLUSIONS: The use of mild α-chymotrypsin treatment of semen samples in case of hyperviscosity does not appear to impact negatively on the fertilization rates after ART and could be regarded as an additional method to induce liquefaction of highly viscous semen samples in IVF.

Effect on surgical decisions: Ulipristal acetate as key player in Belgian phase IV registration trial.

OBJECTIVE: To observe alterations in surgical planning that were due to the use of ulipristal acetate (UPA) 5 mg daily for symptomatic uterine fibroids. METHODS: A prospective cohort trial involving women with symptomatic fibroids was undertaken in 23 clinical practice sites within Belgium between October 1, 2014, and March 31, 2016, to compare initial surgical planning to performed surgical procedures following the use of UPA 5 mg daily for 3 months. Secondary outcomes were surgical complications, reduction in fibroids, bleeding control, and adverse effects. RESULTS: Two hundred and twenty-two women were recruited for the trial. The requirement for surgery decreased with the use of UPA, with 54% of women undergoing surgery after treatment. The reduction in surgery performed was lower for women willing to conceive (40%) compared to women who were not (49%). The volume of the fibroids decreased significantly, with the largest measured fibroid decreasing by 50%. Bleeding and pain were significantly decreased with the use of UPA. No major complications were recorded, and no liver function abnormalities were reported during the treatment and in follow-up. CONCLUSION: By administering UPA, the required rate of surgery was significantly decreased. Also, the resulting reduction in size of the fibroids could have the potential benefit of reducing surgery-related complications, and long-term use may be warranted to avoid surgery completely.

Long-Term Assessment of a Prospective Cohort of Patients Undergoing Laparoscopic Sacrocolpopexy.

OBJECTIVE: To report long-term outcomes after laparoscopic sacrocolpopexy. METHODS: We conducted a prospective descriptive cohort study on 331 consecutive patients who underwent laparoscopic sacrocolpopexy for symptomatic prolapse (Pelvic Organ Prolapse Quantification [POP-Q] system stage 2 or greater) at one center, with minimum 1.5 years of follow-up by April 30, 2014. Primary outcome measures were Patient Global Impression of Change score and failure at the apex (C≥-1 cm; POP-Q stage 2 or greater). Secondary outcomes were anatomical failure in other compartments, duration of follow-up, occurrence and time point of complications, reinterventions, and functional outcomes by response to a standardized 24-question interview on prolapse and bladder, bowel, and sexual function. Assessment was by an experienced clinician not involved in patient management. RESULTS: The follow-up rate was 84.6% (280/331); 185 of 331 (55.9%) patients were both physically examined and interviewed, and 95 of 331 (25.7%) were interviewed only. The median age at interview was 72 years (interquartile range 13 years), with a follow-up period of 85.5 months (interquartile range 46 months). Approximately 83% (231/280) reported improvement; 5.7% (16/280) were unchanged, 5.7% (16/280) felt slightly worse, and 6.8% (17/280) reported clear deterioration. Anatomical failure at point-C was 8.6% (16/185); anterior (22.2%, 41/185) and posterior (28.6%, 53/185) prolapse were more common than apical prolapse. Of those with level-I anatomical cure, 10.1% (17/185) felt worse; half of them (9/17) because of prolapse in another compartment. The others had urinary problems (41.2%, 7/17), obstructive defecation (11.8%, 2/17), or dyspareunia (11.8%, 2/17). Conversely, the majority of patients with recurrence at the vault (62.5%, 10/16) self-reported to be improved. The reoperation rate was 17.8% (48/270), including 19 (7.0%) for graft-related complications and nine (3.3%) for prolapse. CONCLUSION: More than four out of five patients (82.5%) felt improved 86 months after laparoscopic sacrocolpopexy. Of those not improved, two thirds had recurrent prolapse; however, typically mid-vaginal. The other third reported urinary or bowel problems or dyspareunia. Reintervention for prolapse was 3.3%. The most common reasons for reoperation were graft-related complications (7.0%) and urinary incontinence (6.7%).

Venous Air Embolism during Hysteroscopic Myomectomy: An Analysis of 7 Cases.

Venous air embolism (VAE) is a rare but potentially fatal complication of hysteroscopic myomectomy. The symptoms of VAE range from mild and clinically insignificant to complete cardiovascular collapse during surgery. Anesthesiologists and surgeons should be aware of the clinical characteristics and predisposing factors of this possible adverse event. This report analyzes 7 cases of VAE, which occurred at the University Hospitals Leuven, in patients undergoing hysteroscopic myomectomy from April 2009 to April 2011. Patient and myoma characteristics were compared to a control group of 27 patients who underwent uneventful hysteroscopic myomectomy during the same period of time. Analysis of baseline data including myoma size failed to identify predisposing factors. Clinical events in this series were classified according to their severity as minor (causing respiratory symptoms in 2 cases), moderate (accompanied by hemodynamic instability in 5 cases), or severe (requiring resuscitation in no cases). Case characteristics and therapeutic strategies in all cases were compared to reports from recent literature.

Laparoscopic versus robotic-assisted sacrocolpopexy for pelvic organ prolapse: a systematic review.

The use of robot-assisted surgery (RAS) has gained popularity in the field of gynaecology, including pelvic floor surgery. To assess the benefits of RAS, we conducted a systematic review of randomized controlled trials comparing laparoscopic and robotic-assisted sacrocolpopexy. The Cochrane Library (1970-January 2015), MEDLINE (1966 to January 2015), and EMBASE (1974 to January 2015) were searched, as well as ClinicalTrials.gov and the International Clinical Trials Registry Platform. We identified two randomized trials (n = 78) comparing laparoscopic with robotic sacrocolpopexy. The Paraiso 2011 study showed that laparoscopic was faster than robotic sacrocolpopexy (199 ± 46 vs. 265 ± 50 min; p < .001), yet in the ACCESS trial, no difference was present (225 ± 62.3 vs. 246.5 ± 51.3 min; p = .110). Costs for using the robot were significantly higher in both studies, however, in the ACCESS trial, only when purchase and maintenance of the robot was included (LSC US$11,573 ± 3191 vs. RASC US$19,616 ± 3135; p < .001). In the Paraiso study, RASC was more expensive even without considering those costs (LSC US$ 14,342 ± 2941 vs. RASC 16,278 ± 3326; p = 0.008). Pain was reportedly higher after RASC, although at different time points after the operation. There were no differences in anatomical outcomes, pelvic floor function, and quality of life. The experience with RASC was tenfold lower than that with LSC in both studies. The heterogeneity between the two studies precluded a meta-analysis. Based on small randomized studies, with surgeons less experienced in RAS than in laparoscopic surgery, robotic surgery significantly increases the cost of a laparoscopic sacrocolpopexy. RASC would be more sustainable if its costs would be lower. Though RASC may have other benefits, such as reduction of the learning curve and increased ergonomics or dexterity, these remain to be demonstrated.

A mixture of 86% of CO2, 10% of N2O, and 4% of oxygen permits laparoscopy under local anesthesia: a pilot study.

The aim of this study is to verify that 10 % of N2O in CO2 sufficiently reduces pain to permit laparoscopy under local anesthesia. In nine patients undergoing laparoscopy under local anesthesia for tubal sterilization, a mixture of 86 % of CO2, 10 % of N2O, and 4 % of oxygen (the Gas Mixture) was used for the pneumoperitoneum. For CO2, N2O, and for the Gas Mixture, the pain when blowing over the tongue tip and the pH changes of saline and Hartmann's solution were estimated. In all nine patients, discomfort was minimal and the intervention was well tolerated, similar to 100 % N2O. Tongue tip pain (n = 15), on VAS scale, was lower with 86 % CO2 + 10 % N2O + 4 % O2 (2.4 ± 1.4, P = 0.005) and much lower with 100 % N2O (0.3 ± 0.6, P < 0.0007) than with pure CO2 (3.6 ± 1.7). The pH of saline (n = 5) decreased from 7.00 ± 0.07 to 4.18 ± 0.04 (P = 0.001), 6.98 ± 0.08 (NS), and 4.28 ± 0.04 (P = 0.01) with 100 % CO2, 100 % N2O and the Gas Mixture, respectively. The pH of Hartmann's solution (n = 5) decreased similarly from 7.00 ± 0.07 to 5.18 ± 0.04 (P = 0.01), 7.02 ± 0.19 (NS), and 5.3 ± 0.4 (P = 0.01), respectively. These data demonstrate that a mixture with 10 % of N2O and 4 % of O2 in CO2 permits laparoscopy under local anesthesia. This result cannot be explained by direct irritation estimated by tongue tip pain or by pH changes.

Vaginal expression of efflux transporters and the potential impact on the disposition of microbicides in vitro and in rabbits.

In order to reach sufficiently high tissue concentrations and thus be effective, vaginally applied anti-HIV microbicides that are active at the level of the immune cells must permeate across the cervicovaginal mucosal layer. Cellular efflux transporters, such as Pgp, BCRP, and MRP-2, have been demonstrated to greatly affect drug disposition at different sites in the body including the intestine and the blood-brain barrier; their possible role on drug uptake from the female genital tract, however, has not been elucidated yet. In the present study, the protein expression of Pgp, BCRP, and MRP-2 in endocervical and vaginal tissue of premenopausal women was confirmed by Western blot analysis. To enable the assessment of transporter effects in vitro, the identification of an appropriate cervicovaginal cell line was pursued. The cervical SiHa cell line was observed to express mRNA of the 3 studied transporters, but only MRP-2 was found to be active. Consequently, the established Caco-2 cell line was utilized as an alternative in which the interaction of 10 microbicide candidates with the efflux transporters was studied. Darunavir, saquinavir, and maraviroc were identified as Pgp and MRP-2 substrates. The impact of Pgp on in vivo drug disposition was further examined for the model Pgp substrate talinolol in rabbits. Its vaginal uptake was significantly reduced by Pgp-mediated efflux when formulated in a neutral but not in an acidic gel. Our findings indicate the expression of a functional Pgp transporter in the vaginal mucosa that may severely reduce the vaginal uptake of Pgp substrates, including certain microbicide candidates, especially in women with an increased vaginal pH.

Analysis of the learning process for laparoscopic sacrocolpopexy: identification of challenging steps.

INTRODUCTION AND HYPOTHESIS: We earlier demonstrated that the operation time of laparoscopic sacrocolpopexy (LSCP) by an experienced surgeon drops significantly after 30 cases to reach a steady state after 90. We now aimed to define the learning curve and to identify the most challenging steps for a trainee learning LSCP. METHODS: Prospective consecutive series of 60 patients undergoing LSCP performed by a trainee experienced in operative laparoscopy but not LSCP. Prior to the first case, the trainee primed his endoscopic suturing skills on an endotrainer for 15 h. His operation time and performance score were analysed using moving average analysis (MOA). The former and the occurrence of complications or short-term failures were compared with those of a concurrent control group consisting of patients operated on by a surgeon experienced in LSCP (teacher). The procedure was empirically divided into five consecutive steps (dissection of the promontory, the paracolic gutter and vagina, suturing of the mesh to the vault, stapling to the promontory, and peritonealisation). RESULTS: The MOA of the operation time demonstrated a learning curve for all steps, except for the dissection of and fixation to the promontory. The most time-consuming step is the dissection of the vault, for which it took the trainee 31 procedures to achieve an operation time comparable to that of the teacher. Also, the quality of the dissection improved over time. Suturing of the implant to the vault and peritonealisation took only 10 and 6 procedures respectively. There was no difference in the occurrence of major complications and in one case the trainee asked for assistance. CONCLUSION: Quality of LSCP improves with experience. Operation time falls as well, and the most time-consuming step is the dissection of the paracolic and perivaginal spaces. Prior training in laparoscopic suturing coincided with a short learning process for the phases requiring suturing.

Peritoneal full-conditioning reduces postoperative adhesions and pain: a randomised controlled trial in deep endometriosis surgery.

BACKGROUND: To translate the concept of full-conditioning (FC) from animal experiments to the human, and to evaluate the efficacy for adhesion prevention. FC consisted of decreasing acute inflammation by 86% CO2+ 10% N2O + 4% O2 for the pneumoperitoneum, cooling of the peritoneal cavity, humidification, heparinized rinsing solution and 5 mg of dexamethasone as demonstrated in animal models. METHODS: A randomized controlled trial (RCT: NCT01344486) comparing standard laparoscopy with full conditioning together with a barrier in a 2/3 ratio in 44 women undergoing deep endometriosis surgery at KULeuven. The primary aim was reduction of adhesions. Secondary aims were CO2 resorption, postoperative pain and recovery. Randomization was performed after signing informed consent. Adhesion scoring during second look laparoscopy and pain scoring were done blindly. RESULTS: In the FC group (n = 16) adhesions were completely prevented in 12/16 women whereas in the control group (n = 11) all women had severe adhesions (P < 0.0005). Also the area, density and severity of adhesions were less. (P <0.001). In the control group, severity, density and area of adhesions were strongly interrelated (P = 0.0001 for all areas) suggesting a common enhancing factor. In the FC group CO2 resorption (P < 0.001), postoperative pain (P < 0.001), and CRP concentrations (P < 0.01) were lower while clinical recovery was faster (P < 0.0001) and time to first flatus (P < 0.002) shorter. IN CONCLUSION: This translational research confirms in the human the efficacy of FC in reducing CO2 resorption and adhesions with in addition less postoperative pain, lower postoperative CRP concentrations and an accelerated recovery.

Addition of nitrous oxide to the carbon dioxide pneumoperitoneum strongly decreases adhesion formation and the dose-dependent adhesiogenic effect of blood in a laparoscopic mouse model.

OBJECTIVE: To evaluate the effect of addition of nitrous oxide (N2O) to the carbon dioxide (CO2) pneumoperitoneum (PP) and the effect of blood, plasma, or red blood cells (RBCs) on postoperative adhesions in a laparoscopic mouse model. DESIGN: Prospective randomized controlled trial. SETTING: University laboratory research center. ANIMAL(S): BALB/c female mice. INTERVENTION(S): The effect of adding to the 60-minute CO2 PP 5%, 10%, 25%, 50%, or 100% N2O on adhesion formation was evaluated. Subsequently the effect of adding 1 mL blood, or RBCs, or plasma and the effect of adding different concentrations of blood were studied. Finally, the effect of adding 10% N2O, 4% O2, or both to the CO2 was evaluated in a control group and after addition of blood. MAIN OUTCOME MEASURE(S): Postoperative adhesions after 7 days. RESULT(S): N2O strongly reduces adhesion formation with a full effect at a concentration of 5% or 10%. Adhesions increase linearly with 0.125 mL to 1 mL blood. In both the control group and after adding blood, 10% N2O is the most effective factor in prevention of adhesions. CONCLUSION(S): N2O, from concentrations of 5% upward, strongly prevents adhesion formation. Blood, mainly the plasma, increases adhesion formation. These data extend the concept of the role of acute inflammation and support the importance of good surgical practice with little bleeding and peritoneal cavity conditioning in adhesion prevention.

Intraperitoneal temperature and desiccation during endoscopic surgery. Intraoperative humidification and cooling of the peritoneal cavity can reduce adhesions.

This study was conducted to document quantitatively the intraperitoneal temperature and desiccation during laparoscopic surgery. The temperature, relative humidity, and flow rate were measured in vitro and during laparoscopic surgery, at the entrance and at the exit of the abdomen. This permitted us to calculate desiccation for various flow rates using either dry CO(2) or CO(2) humidified with 100% relative humidity at any preset temperature between 25 and 37°C. The study showed that desiccation, both in vitro and in vivo, varies as expected with the flow rates and relative humidity while intraperitoneal temperature varies mainly with desiccation. Temperature regulation of bowels is specific and drops to the intraperitoneal temperature without affecting core body temperature. With a modified humidifier, desiccation could be eliminated while maintaining the intraperitoneal temperature between 31 to 32°C.

The impact of the learning curve on adhesion formation in a laparoscopic mouse model.

OBJECTIVE: To evaluate the impact of surgeon training on adhesion formation in a laparoscopic mouse model. Laparoscopic surgery and bowel manipulation was demonstrated to enhance postoperative adhesion formation. DESIGN: Prospective randomized, controlled trial. SETTING: University laboratory research center. ANIMAL(S): 200 BALB/c and 200 Swiss female mice. INTERVENTION(S): Adhesions were induced by opposing bipolar lesions and 60 minutes of pneumoperitoneum. Each surgeon operated on 80 mice (40 Swiss and 40 BALB/c), the only variable thus being his/her increasing experience. Some surgeons were already experienced gynecologists, others were starting their training. MAIN OUTCOME MEASURE(S): End points were the duration of surgery while performing the lesions. The adhesion formation was scored quantitatively (proportion and total) and qualitatively (extent, type, and tenacity) after 7 days. RESULT(S): With training, duration of surgery and adhesion formation decreased exponentially for all surgeons, whether experienced or not. Experienced surgeons had initially a shorter duration of surgery, less adhesion formation, and less de novo adhesions than inexperienced surgeons. CONCLUSION(S): These data suggest that laparoscopic skills improve with training, leading to a decrease in the duration of surgery and formation of adhesions. Therefore completion of a standardized learning curve should be mandatory when initiating adhesion formation studies both in laboratory or clinical setting.

Postoperative inflammation in the abdominal cavity increases adhesion formation in a laparoscopic mouse model.

OBJECTIVE: To investigate acute inflammation in the peritoneal cavity in adhesion formation. DESIGN: Prospective randomized, controlled trial. SETTING: University laboratory research center. ANIMAL(S): 9- to 10-week-old BALB/c female mice. INTERVENTION(S): In a laparoscopic mouse model, acute inflammation in the peritoneal cavity evaluated in CO(2) pneumoperitoneum enhanced adhesions, by CO(2) pneumoperitoneum plus manipulation, and in the latter group plus dexamethasone. MAIN OUTCOME MEASURE(S): Qualitative and quantitative adhesion scores and an acute inflammation score (neoangiogenesis, diapedesis, and leukocyte accumulation). RESULT(S): Adhesions at the lesion site were enhanced by the CO(2) pneumoperitoneum, further enhanced by manipulation, and decreased by the administration of dexamethasone. The acute inflammation scores (total, neoangiogenesis, diapedesis, and leukocyte accumulation) strongly correlated with the total adhesion score. Inflammation scores were similar at both the surgical lesion and the parietal peritoneum. CONCLUSION(S): Acute inflammation of the entire peritoneum cavity is an important mechanism involved in adhesion formation and enhances adhesion formation at the lesion site.