Live birth rate after female fertility preservation for cancer or haematopoietic stem cell transplantation: a systematic review and meta-analysis of the three main techniques; embryo, oocyte and ovarian tissue cryopreservation.

STUDY QUESTION: What are the chances of achieving a live birth after embryo, oocyte and ovarian tissue cryopreservation (OTC) in female cancer survivors? SUMMARY ANSWER: The live birth rates (LBRs) following embryo and oocyte cryopreservation are 41% and 32%, respectively, while for IVF and spontaneous LBR after tissue cryopreservation and transplantation, these rates are 21% and 33%, respectively. WHAT IS KNOWN ALREADY: Currently, fertility preservation (FP) has become a major public health issue as diagnostic and therapeutic progress has made it possible to achieve an 80% survival rate in children, adolescents and young adults with cancer. In the latest ESHRE guidelines, only oocyte and embryo cryopreservation are considered as established options for FP. OTC is still considered to be an innovative method, while it is an acceptable FP technique in the American Society for Reproductive Medicine guidelines. However, given the lack of studies on long-term outcomes after FP, it is still unclear which technique offers the best chance to achieve a live birth. STUDY DESIGN, SIZE, DURATION: We performed a systematic review and meta-analysis of published controlled studies. Searches were conducted from January 2004 to May 2021 in Medline, Embase and the Cochrane Library using the following search terms: cancer, stem cell transplantation, FP, embryo cryopreservation, oocyte vitrification, OTC and reproductive outcome. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 126 full-text articles were preselected from 1436 references based on the title and abstract and assessed via the Newcastle-Ottawa Quality Assessment Scale. The studies were selected, and their data were extracted by two independent reviewers according to the Cochrane methods. A fixed-effect meta-analysis was performed for outcomes with high heterogeneity. MAIN RESULTS AND THE ROLE OF CHANCE: Data from 34 studies were used for this meta-analysis. Regarding cryopreserved embryos, the LBR after IVF was 41% (95% CI: 34-48, I2: 0%, fixed effect). Concerning vitrified oocytes, the LBR was 32% (95% CI: 26-39, I2: 0%, fixed effect). Finally, the LBR after IVF and the spontaneous LBR after ovarian tissue transplantation were 21% (95% CI: 15-26, I2: 0%, fixed-effect) and 33% (95% CI: 25-42, I2: 46.1%, random-effect), respectively. For all outcomes, in the sensitivity analyses, the maximum variation in the estimated percentage was 1%. LIMITATIONS, REASONS FOR CAUTION: The heterogeneity of the literature prevents us from comparing these three techniques. This meta-analysis provides limited data which may help clinicians when counselling patients. WIDER IMPLICATIONS OF THE FINDINGS: This study highlights the need for long-term follow-up registries to assess return rates, as well as spontaneous pregnancy rates and birth rates after FP. STUDY FUNDING/COMPETING INTEREST(S): This work was sponsored by an unrestricted grant from GEDEON RICHTER France. The authors have no competing interests to declare. REGISTRATION NUMBER: CRD42021264042.

[Oncofertility and breast cancer at Montpellier University Hospital: Retrospective analysis of patients management since 2011]. / Oncofertilité et cancer du sein au CHRU de Montpellier : analyse rétrospective du devenir des patientes depuis 2011.

OBJECTIVE: Five to 7% of breast cancers affect women under 40 years old. The survival of these patients has been improved thanks to therapeutic advances, often to the detriment of their fertility. The objective of this study is to evaluate the activity of oncofertility and the future of young women with breast cancer managed at the Montpellier University Hospital. METHODS: This is a retrospective study including women aged from 18 to 43 years-old diagnosed with breast cancer and referred in oncofertility consultation at the Montpellier University Hospital between July 2011 and December 2018. RESULTS: 190 patients were eligible, three refused to participate to the study, hence 187 patients were included. We estimate that only 33% of young breast cancer patients potentially eligible for fertility preservation (FP) benefited from an oncofertility consultation in our region. Of these 187 patients, 58 (31%) underwent ovarian stimulation for oocyte or embryo vitrification. They were significantly younger: 32.9 vs 34.6 years old (P=0.01) and had fewer invaded lymph nodes. A total of 66 cycles were achieved and 11.4 oocytes or 3 embryos were vitrified per patient. The reuse rate was 3.6% with 91% of post cancer pregnancies being spontaneous. CONCLUSION: The oncofertility care network seems effective at the regional level. Enhancing health professionals' awareness and creating a regional register could improve our long-term follow-up.

[Optimizing training in limited obstetric ultrasound for midwives through a combination of e-learning and simulation]. / E-learning et simulation en échographie focalisée pour la formation continue des sages-femmes en salle de naissance.

OBJECTIVE: To evaluate a training program in limited obstetric ultrasound, combining e-learning and simulation. METHODS: This a descriptive cohort study in Single-center study conducted in a French university hospital. Thirty-three practicing midwives who had not received basic training in ultrasonography had unlimited access to an e-learning platform offering interactive theoretical instruction modules. Then, they attended a one-day simulator-based obstetric ultrasound workshop. A theoretical competency test was taken before the e-learning component (T1), then before (T2) and after (T3) the simulation workshop. Their competency in specific practical tasks was assessed before and after the workshop. A learner satisfaction questionnaire was completed after the program. RESULTS: The mean score obtained in the theoretical competency test was 46.6% (range 8.3-83.3%) at T1, 87.2% (66.6-100%) at time T2, and 91.6% (66.6-100%) at T3. Significant improvements were observed between times T1 and T2 (P<0.001) or T3 (P<0.001), as well as in the performance of certain practical tasks, such as placental location (P=0.02) and visualization of the cervix (P=0.03). The mean number of logins to the e-learning platform during the program was 11.2 per participant (6-24). Most participants were satisfied with the training and reported an improvement in their daily practice. CONCLUSION: Training in limited obstetric ultrasound, combining e-learning to acquire theoretical knowledge and a hands-on simulation workshop, appears to meet the needs of practicing midwives. Most participants were satisfied with the proposed teaching and the rapid acquisition of ultrasound skills applicable to their clinical practice.

[Natural cycle for frozen-thawed embryo transfer: Spontaneous ovulation or triggering by HCG]. / Transferts d'embryons congelés en cycle naturel : ovulation spontanée ou déclenchement par hCG ?

OBJECTIVE: To compare frozen-thawed embryo transfer (FET) outcomes in natural cycles according to ovulation induction: spontaneous versus recombinant human chorionic gonadotrophin (r-hCG) triggering. METHODS: This retrospective study included all patients monitored for natural cycle FET during one year. When serial monitoring were performed until spontaneous LH rise, patients were included in group A (n=38) whereas those receiving r-hCG for ovulation triggering formed group B (n=43). All embryos had been cryopreserved by a vitrification method following a previous IVF cycle. No luteal phase support had been given. We compared outcomes between the 2 groups. RESULTS: After checking groups comparability, we didn't find significant difference for the implantation rate, clinical pregnancy rate and live birth (31% vs 45%, 32% vs 51% et 21% vs 32%, respectively for group A and B). The number of monitoring was significantly lower in group B (1,9±0,8 versus 2,5±1, P=0,006). DISCUSSION: Although no consensus has been yet established, natural cycle seems indicated for normo-ovulating patients but the question of ovulation induction is still debated. In our study, triggering ovulation by r-hCG, respecting strict criteria, seems provide good results while reducing both protocol's constraints and cost.

[What measures of perineal protection at birth are consensual in France? Results of a Delphi survey]. / Quelles mesures de protection périnéale à l'accouchement sont consensuelles en France ? Résultats d'une enquête Delphi.

OBJECTIVE: To evaluate expert's opinion in order to obtain a consensus on the different measures of perineal protection at the time of vaginal delivery. METHODS: A survey using the Delphi method was carried out with a panel of French obstetricians, urogynecologists and midwives. The questionnaire included 22 questions grouped into four groups: expulsive efforts, indications of episiotomy, episiotomy repair and other forms of perineal protection. The experts had to answer on a 9-point scale, both on the validity and the clarity of each proposal. After analysis of the replies of the first round, a second round was sent to the same experts for certain proposals. Each turn was the subject of two raises. To be validated, each proposal had to obtain a median equal to or greater than 7/9 and an agreement between the experts greater than 65% in the first round, and more than 75% in the second round. RESULTS: The study was conducted between March and October 2016. Of the 300 experts initially selected, 93 (31%) responded to the first round, including 63 obstetricians (67.7%), 12 urogynecologists (12.9%) and 18 midwives (19.4%). In the second round, 72 experts replied, representing 77.4% of the experts who also answered the first round. At the end of the two rounds, 11 proposals were validated, and 11 rejected. The following recommendations have been validated. Uterine expression should be proscribed. The two modes of pushing (blocked in Valsalva and by blowing) can be indifferently proposed, in case of fetal progression and in the absence of fetal distress. The midline episiotomy should be proscribed. The medio-lateral (or lateral) episiotomy should be left to the discretion of the accoucheur. The maintenance of the fetal head with one hand must be systematic to the expulsion to protect the perineum. Repair of the episiotomy should be made (except in some cases) with a rapid absorbable suture. The prescription of NSAIDs and/or painkillers of level 2 should be preferred to reduce the pain of post-natal perineal scars. CONCLUSION: Several measures of perineal protection at the time of vaginal delivery are consensual in France. Other measures should be studied further. LEVEL OF EVIDENCE: 4.

Cranberry capsules to prevent nosocomial urinary tract bacteriuria after pelvic surgery: a randomised controlled trial.

OBJECTIVE: To evaluate whether cranberries are able to prevent postoperative urinary bacteriuria in patients undergoing pelvic surgery and receiving transurethral catheterisation. DESIGN: Randomised, double-blind, placebo-controlled trial. SETTINGS: French tertiary Care centre, University Hospital. POPULATION: A total of 272 women undergoing pelvic surgery aged 18 or older. METHODS: Participants undergoing pelvic surgery were randomised to 36 mg cranberry (proanthocyanidins, PAC) or placebo once daily for 10 days. Statistical analysis was performed by a chi-square test. MAIN OUTCOME MEASURES: The primary and secondary outcomes were postoperative bacteriuria, defined by a positive urine culture, within the first 15 and 40 days, respectively. RESULTS: Two hundred and fifty-five participants received the intended treatment: 132 (51.8%) received PAC and 123 (48.2%) received placebo. There were no significant differences in baseline demographics, intra-operative characteristics or duration and type of catheterisation between the two groups. PAC prophylaxis did not reduce the risk of bacteriuria treatment within 15 days of surgery [27% bacteriuria with PAC compared with 25% bacteriuria with placebo: relative risk 1.05, 95% CI 0.78-1.4, P = 0.763). The same result was observed on day 40. Bacteriuria occurred more often in older women with increased length of catheterisation. CONCLUSION: Immediate postoperative prophylaxis with PAC does not reduce the risk of postoperative bacteriuria in patients receiving short-term transurethral catheterisation after pelvic surgery. TWEETABLE ABSTRACT: PAC prophylaxis does not reduce the risk of postoperative bacteriuria in patients undergoing pelvic surgery.

Evaluation of in vivo properties of Velosorb™ fast versus Vicryl™ rapide in a functional rabbit model of intradermic suture and episiotomy.

OBJECTIVE: Fast-absorbing polyglactin 910 is commonly used to suture skin and vaginal incisions. In vitro studies have shown similar tensile strength properties between Velosorb™ Fast and Vicryl™ Rapide (Al-Qattan MM. J Hand Surg Br Eur. 2005;30(1):90-91). This randomized study compared Velosorb™ Fast (Covidien) with Vicryl™ Rapide (Ethicon) in a rabbit model of intradermic suture and episiotomy. MATERIALS AND METHODS: This randomized prospective study was performed on 20 New Zealand rabbits, in which we realized a mediolateral perineo-vaginal incision and two vertical skin incisions of about 8 cm on the abdominal wall. The sutures were randomized between Velosorb™ Fast (Covidien) and Vicryl™ Rapide (Ethicon), and each rabbit was treated with the same suture on both vaginal incision and left abdominal incision, while the right abdominal incision was closed with an alternate suture. A macroscopic examination was performed on days 5 and 11. On day 11, animals were sacrificed for histological (Badylak quantitative score) and electron microscopic examinations. Differences were considered significant at p < .05. RESULTS: All of the rabbits survived and were included in the final results. Fifty-one sutures were visible by histologic analysis (27 in the Velosorb™ Fast group and 24 in the Vicryl™ Rapide group). The power of the study was ≥80%. There was no significant difference between the two groups based on the total histologic Badylak score analysis or the Badylak sub-score analysis. CONCLUSIONS: Velosorb™ Fast seems to be as efficient as Vicryl™ Rapide for use in perineal and skin closure.

[Prevention and treatment of intra-uterine synechiae: Review of the literature]. / Prévention et traitement des synéchies endo-utérines : revue de la littérature.

Intra-uterine adhesions are a major cause of secondary infertility. The prevalence of adhesions is probably underestimated due to the heterogeneity of the symptoms. An exhaustive literature search using search engines MEDLINE, Pubmed, Cochrane library and Web of Science was performed to make a focus on the origins, consequences and methods of prevention of intra-uterine adhesions. Intra-uterine adhesions are likely to occur after any endo-uterine surgery via dysregulated activation of coagulation chain linked to the inflammatory process. Early and late obstetric complications are also recognized as caused by adhesions. The diagnosis is currently performed by hysteroscopy but it remains an invasive procedure even if it can be done with an ambulatory management. Several research approaches inspired by intra-abdominal surgery for the prevention of pelvic adhesions have been developed. However, no current method of prevention has proven its effectiveness in terms of improving spontaneous fertility. The improvement in surgical practices, the design of new intra-uterine medical devices and new research especially in the field of endometrial stem cells can maybe reduce the rate of adhesions end their complications after intra-uterine surgery.

Evaluation of a laparoscopic training program with or without robotic assistance.

The aim of the present study was to evaluate the value of a box trainer simulator in laparoscopy training. A further aim was to determine if robotic-assisted approaches further improved the young residents' skills in laparoscopic surgery. The study was a prospective randomized study. Twelve residents in obstetrics & gynecology completed four laparoscopy-related procedures of varying complexity using a box trainer simulator. Participants were randomized into two groups; robotic-assisted laparoscopy (LRA) and traditional laparoscopy (TL). All subjects were assessed with a time and technical score, which are quantitative and qualitative approaches (respectively). All residents completed the training and a satisfaction questionnaire, which confirmed that the training was well regarded. Regardless of the workshop type, there was a clear time and technical improvement for the difficult tasks. The improvement of time score was most apparent for simple tasks in LRA and for more complex tasks in TL. After training, we did not find a significant difference for the technical score between Novices and Experts in TL and LRA. These findings suggest that training in laparoscopy surgery is useful, reproducible and well accepted by both novice and more advanced trainees. Furthermore, gynecological endoscopy center consider including robotic-assisted approaches in their surgical training program.

[Congenital cervical agenesis: pregnancy after transmyometrial embryo transfer]. / Agénésie cervicale congénitale: grossesse obtenue après transfert intra-myométrial d'embryon.

Cervical agenesis is a rare congenital pathology linked to an anomaly of development of the Mullerian system. We described a case report about a 22-year old woman, consulting for infertility, who had a complete cervical agenesis. The first evaluation suggested a 46 XX karyotype and a normal ovarian reserve. The surgical examination confirmed the absence of cervix with impossibility of catheterization. She became pregnant thanks to an in vitro fertilization (IVF) with transmyometrial embryo transfer. Caesarean was decided at 36 weeks of gestation (WG) due to spontaneous uterine contractions. An injection of medroxyprogesterone was made after the placenta delivery in order to warning the partum hemorrhage. The ultrasound examination, realized 15 days after caesarean, underlined a good uterine involution. The surgery by cervico-vaginal anastomosis can be offered to patients because it offers chances of spontaneous pregnancies. But this surgery exposes women to a risk of failure, and of severe complications such as pain or infection, and might end in a hysterectomy. By choosing the transmyometrial transfer by vaginal way, the patient was exposed to the risk of spontaneous miscarriage. It was raising the problem of the uterine evacuation. This delivery after 34 WG is encouraging for the infertility by cervical agenesis.

Prospective ultrasonographic follow-up of synthetic mesh in cohort of patients after vaginal repair of cystocele.

OBJECTIVE: We sought to validate a sequence of ultrasonographic mesh measurements to determine the relevant time points in the postoperative monitoring of mesh size. METHODS: Mesh was measured preoperatively ex vivo, prior to insertion, in 25 patients scheduled to undergo vaginal repair of cystocele involving insertion of a Ugytex™ transobturating polypropylene mesh. A 2D/3D perineal ultrasound scan was performed at the end of the surgical procedure (D0), then on third day after surgery (D3) and 6 weeks (W6) after the operation. Medio-sagittal view was used to measure mesh total length and the sagittal arc (length between the most distant points of the mesh). RESULTS: Time-course changes in sagittal arc were marked by a 8% increase on D3 (with respect to D0) and a 20% decrease at W6 (with respect to D3). Mesh total length at W6 on average corresponded to 74% (±20) of mesh total length measured on D3. CONCLUSION: This study showed the changes in the mesh ultrasonographic measurements following vaginal placement by vaginal route. The D3 ultrasound scan should appear to be suitable as a reference for subsequent ultrasonographic monitoring.