Impact of endometrial preparation on early pregnancy loss and live birth rate after frozen embryo transfer: a large multicenter cohort study (14 421 frozen cycles).

STUDY QUESTION: Does the endometrial preparation protocol (artificial cycle (AC) vs natural cycle (NC) vs stimulated cycle (SC)) impact the risk of early pregnancy loss and live birth rate after frozen/thawed embryo transfer (FET)? SUMMARY ANSWER: In FET, ACs were significantly associated with a higher pregnancy loss rate and a lower live birth rate compared with SC or NC. WHAT IS KNOWN ALREADY: To date, there is no consensus on the optimal endometrial preparation in terms of outcomes. Although some studies have reported a higher pregnancy loss rate using AC compared with NC or SC, no significant difference was found concerning the pregnancy rate or live birth rate. Furthermore, no study has compared the three protocols in a large population. STUDY DESIGN SIZE DURATION: A multicenter retrospective cohort study was conducted in nine reproductive health units in France using the same software to record medical files between 1 January 2012 and 31 December 2016. FET using endometrial preparation by AC, modified NC or SC were included. The primary outcome was the pregnancy loss rate at 10 weeks of gestation. The sample size required was calculated to detect an increase of 5% in the pregnancy loss rate (21-26%), with an alpha risk of 0.5 and a power of 0.8. We calculated that 1126 pregnancies were needed in each group, i.e. 3378 in total. PARTICIPANTS/MATERIALS SETTING METHODS: Data were collected by automatic extraction using the same protocol. All consecutive autologous FET cycles were included: 14 421 cycles (AC: n = 8139; NC: n = 3126; SC: n = 3156) corresponding to 3844 pregnancies (hCG > 100 IU/l) (AC: n = 2214; NC: n = 812; SC: n = 818). Each center completed an online questionnaire describing its routine practice for FET, particularly the reason for choosing one protocol over another. MAIN RESULTS AND THE ROLE OF CHANCE: AC represented 56.5% of FET cycles. Mean age of women was 33.5 (SD ± 4.3) years. The mean number of embryos transferred was 1.5 (±0.5). Groups were comparable, except for history of ovulation disorders (P = 0.01) and prior delivery (P = 0.03), which were significantly higher with AC. Overall, the early pregnancy loss rate was 31.5% (AC: 36.5%; NC: 25.6%; SC: 23.6%). Univariable analysis showed a significant association between early pregnancy loss rate and age >38 years, history of early pregnancy loss, ovulation disorders and duration of cryopreservation >6 months. After adjustment (multivariable regression), the early pregnancy loss rate remained significantly higher in AC vs NC (odds ratio (OR) 1.63 (95% CI) [1.35-1.97]; P < 0.0001) and in AC vs SC (OR 1.87 [1.55-2.26]; P < 0.0001). The biochemical pregnancy rate (hCG > 10 and lower than 100 IU/l) was comparable between the three protocols: 10.7% per transfer. LIMITATIONS REASONS FOR CAUTION: This study is limited by its retrospective design that generates missing data. Routine practice within centers was heterogeneous. However, luteal phase support and timing of embryo transfer were similar in AC. Univariable analysis showed no difference between centers. Moreover, a large number of parameters were included in the analysis. WIDER IMPLICATIONS OF THE FINDINGS: Our study shows a significant increase in early pregnancy loss when using AC for endometrial preparation before FET. These results suggest either a larger use of NC or SC, or an improvement of AC by individualizing hormone replacement therapy for patients in order to avoid an excess of pregnancy losses. STUDY FUNDING/COMPETING INTERESTS: The authors declare no conflicts of interest in relation to this work. G.P.-B. declares consulting fees from Ferring, Gedeon-Richter, Merck KGaA, Theramex, Teva; Speaker's fees or equivalent from Merck KGaA, Ferring, Gedeon-Richter, Theramex, Teva. N.C. declares consulting fees from Ferring, Merck KGaA, Theramex, Teva; Speaker's fees or equivalent from Merck KGaA, Ferring. C.R. declares a research grant from Ferring, Gedeon-Richter; consulting fees from Gedeon-Richter, Merck KGaA; Speaker's fees or equivalent from Merck KGaA, Ferring, Gedeon-Richter; E.M.d'A. declares Speaker's fees or equivalent from Merck KGaA, MSD, Ferring, Gedeon-Richter, Theramex, Teva. I.C-D. declares Speaker's fees or equivalent from Merck KGaA, MSD, Ferring, Gedeon-Richter, IBSA. N.M. declares a research grant from Merck KGaA, MSD, IBSA; consulting fees from MSD, Ferring, Gedeon-Richter, Merck KGaA; Speaker's fees or equivalent from Merck KGaA, MSD, Ferring, Gedeon-Richter, Teva, Goodlife, General Electrics. TRIAL REGISTRATION NUMBER: N/A.

Ethanol sclerotherapy: a treatment option for ovarian endometriomas before ovarian stimulation.

Several surgical treatment modalities have been described in cases of isolated or multiple ovarian endometriotic cysts. The aim of this preliminary study was to investigate and test the efficacy of ethanol sclerotherapy (EST) for recurrent endometriotic cysts, before ovarian stimulation in infertile patients with an adequate ovarian status. In the setting of a prospective comparative study, EST was proposed to 31 infertile patients with recurrence of ovarian endometriomas before inclusion in assisted reproduction cycles. Reproductive outcome was compared with that of patients who had previous laparoscopic cystectomy for recurrent endometriomas. The mean size of endometriomas treated with sclerotherapy was 38.6 +/- 11.2 mm in diameter. Ovarian cysts recurred in 12.9% of cases; at a mean time of 10 months after EST. Ovarian reserve and ovarian response to stimulation were better in the EST group than in the control group. Consequently, clinical and cumulative pregnancy rates of the study group were higher than those of the control group (48.3% versus 19.2%, P = 0.04; and 55.2% versus 26.9%, P = 0.03, respectively). Ethanol sclerotherapy may be a good alternative to surgical management of recurrent endometriotic cysts before assisted reproductive treatment. It could be advised for selected infertile patients.

Anatomical causes of difficult embryo transfer during in vitro fertilization.

OBJECTIVES: Identify, define and validate through statistical analysis the anatomical causes of difficult embryo transfers (ET). MATERIALS AND METHODS: This observational study, carried out in 306 IVF candidates, compared the frequency of anatomical anomalies of the uterus and cervix in women who underwent an easy ET with that in women who underwent a difficult ET. Anatomical anomalies were detected during an assessment of the cervix and uterus including transvaginal ultrasound, hysteroscopy and a mock transfer. Ease of ET was determined during the actual transfer procedure. RESULTS: An easy ET was achieved in 151 patients, whereas difficulties occurred in 155 patients, among whom 55 patients underwent a "very difficult" ET. The most common anatomical characteristics associated with difficult ET were abnormal crypts in the cervical canal (86%) and tortuosity of the cervical canal (68%). Less frequent causes included: internal os contractions (28%) and pronounced anteversion of the uterus (26%). Very difficult ETs were associated with the presence of several causes. CONCLUSIONS: ET is the clinical step that has the most effect on IVF outcome. Difficult transfers are associated with a fall in pregnancy rates. The anatomical causes of difficult transfer identified in this study led to major changes in transfer procedure in our department and to the development of more adapted catheters.

Transvaginal ultrasound-guided embryo transfer in IVF.

OBJECTIVES: To determine whether transvaginal ultrasound-guided embryo transfer is a technique that can be used routinely, whether it improves IVF outcomes and whether it makes difficult transfers easier and more successful. MATERIAL AND METHOD: Non-randomized retrospective study conducted between 2012 and 2016 in the fertility center of the Diaconesses-Croix St-Simon hospital group. The outcomes of 3910 transfers, performed by 5 senior operators, under transabdominal ultrasound guidance are compared with those of 800 transfers, performed by 1 senior operator under transvaginal ultrasound guidance. The criteria studied are the feasibility of the technique and the percentage of pregnancies per transfer in the two populations described, as well as in the difficult and very difficult transfer populations. RESULTS: All the transfers were feasible under transvaginal ultrasound guidance without the use of forceps or additional instruments. The percentage of pregnancies per transfer is significantly increased, when the transfer is performed under transvaginal ultrasound guidance compared with that performed under transabdominal ultrasound guidance, in the general population (38%, n=800 vs 30%, n=3910; P 0.0004) and in the reference population characterized by age <38 years and >6 oocytes collected per puncture (45%, n=490 vs 36%, n=1968; P 0.002). The percentage of pregnancies per transfer (P/T) is not significantly different in the populations of easy transfers (n 695, 38% P/T), difficult transfers (n 58, 46% P/T; P=ns) and very difficult transfers (n 47, 34% P/T; P=ns). CONCLUSIONS: Embryo transfer is a key stage in IVF, in which the quality of performance determines the outcome. In this study, transvaginal ultrasound guidance of the transfer, which is the reference procedure in gynaecological imaging, significantly increases the percentage of pregnancies per transfer, both in the general population and in the reference population, compared with transfers performed under transabdominal ultrasound guidance. Transvaginal ultrasound facilitates the performance of difficult transfers and in particular achieves outcomes in these situations that are not significantly different from those of easy transfers. Visual monitoring of transcervical passage, which is rendered more precise and less traumatic and precision of embryo deposition are the factors that probably account for the improvement in outcomes.

[Isolated congenital aplasia of the anterior cruciate ligament treated by reconstruction in a 5-year-old boy]. / Agénésie isolée du ligament croisé antérieur traitée par ligamentoplastie à l'âge de 5 ans.

Agenesia of the anterior cruciate ligament is a rare entity which is exceptionally symptomatic. We report a case observed in a 5-year-old boy who presented an unstable knee which was treated by Clocheville ligamentopàlasty. At five years followup, the functional outcome was satisfactory. The patient was symptom free and practiced sports activities. He did not develop any complications excepting flexion which was limited to 130 degrees . Magnetic resonance imaging demonstrated good integration of the autograft. Anterior instability in the child limits physical activity and can cause meniscal injury and early osteoarthritis. The Clocheville technique is adapted for pediatric patients with knee instability caused by a congenital defect or injury.

[Twins after ART]. / Grossesses gémellaires après AMP.

From 1986 to 2002, 16,618 twin babies have been reported to FIVNAT. Mean length of gestation was 36.74 weeks. The mean weight was 2413 g and mean height 46 cm. The proportion of prematurity under 28 weeks of amenorrhea was 1.17% and under 33 weeks: 7.78%. These data are similar to those reported in the French AUDIPOG Report.

[Single-plane external fixation of fresh fractures of the femur: critical analysis of 53 cases]. / La fixation externe monoplan dans les fractures récentes du fémur: etude critique d'une série de 53 cas.

PURPOSE OF THE STUDY: External fixation has not been widely used for femoral fractures and few series are reported in the literature. External fixation is generally reserved for severe open fractures, for vessel injury or multiple trauma with life threatening. We present a retrospective analysis of a serie treated in a single center in order to detail the indications of this fixation technique. MATERIAL AND METHODS: From 1984 to Jun 2002, 49 patients with femoral fractures were treated by external fixation. The series included 36 men and 13 women, mean age 31 years. All were victims of high-energy trauma: traffic accident (n = 40), fall from high level (n = 4), firearm wound (n = 5). Multiple fractures were present in all patients except seven and 24 patients had multiple injuries. Forty fractures were open fractures: two type 1, ten type 2, four type 3a, 23 type 3b and five type 3c in the Gustilo classification. Twenty-seven were shaft fractures and 26 involved the distal metaphyseoepiphyseal portion of the femur. Loss of cortical stock was noted in five cases and total loss of a segment in four. Surgery was deferred in 19 patients, mean six days. A single-plane external fixation was used (Orthofix) with a femorofemoral frontolatateral assembly. Transepiphyseal screw fixation was also used to stabilize the distal fracture in eleven cases. RESULTS: One patient with a bifocal fracture of the femur died from head trauma. Three patients required above knee amputation after failure of a vessel bypass or due to septic necrosis of the reconstruction flap. Five patients required a second reduction within days of external fixation. On the AP view, femoral alignment was successfully reestablished at +/- 5 degrees in 45 cases, ranged from 5 degrees to 10 degrees in seven and was greater than 10 degrees in one. On the lateral view, alignment was between 5 degrees and 10 degrees in 42 cases and greater than 10 degrees in one. Femur length was equal to the healthy side in 23 cases, and was shortened 1-2 cm in 26. Four metaphyseal fractures resulted in a 3 cm shortening. Bone healing time was available for 42 patients (1 death, 3 amputations, 3 lost to follow-up). Elective conversion to internal fixation was performed in ten patients (five lateral cortical plates and five centromedullary nailings). These patients all achieved first-intention bone healing with a mean time of 7.4 months. Exclusive external fixation was planned for 34 fractures. First-intention healing was achieved in 25 (17 shaft and 8 distal) without bone graft with an average time of 7.3 months. Ten patients had one or more osteitis foci on pin tracts. Two patients in this group developed recurrent fracture after removal of the external fixator. Nine fractures did not heal and required revision with centromedullary nailing (n = 5) or plate fixation with autograft (n = 4). Nailings for nonunion were successful but plate fixation was compromised by infection in one patient and recurrent fracture after plate removal in another. Fourteen patients underwent joint mobilization under general anesthesia and 14 had open arthrolysis. Mean follow-up was 2.8 years. Mean active flexion was 90 degrees (30-130 degrees). Ten patients exhibited flexion between 30 degrees and 60 degrees and 19 between 70 degrees and 100 degrees. Knee flexion was greater than 110 degrees in 15 patients. Residual 10 degrees flexion was noted in six knees. Mean leg length discrepancy was 0.4 +/- 0.6 after distal fracture and 0.8 +/- 1.3 after diaphyseal fracture. DISCUSSION: The indications and results of external fixation in this series are in line with reports in the literature. For diaphyseal fractures, healing is long and difficult, partly because of the insufficient mechanical properties of external fixation. The rate of infection and stiff knee is high, particularly for distal fractures of the femur. CONCLUSION: External fixation remains the only solution to stabilize certain open diaphyseal fractures or for patients with life-threatening multiple injuries. This techniques allows control of the other traumatic lesions while waiting for internal fixation. For fractures of the distal femur, external fixation can only be advocated for metaphyseodiaphyseal fractures with an intact or reconstructed epiphyseal portion.

[Women of 40 and older in i.v.f. and i.c.s.i.: the FIVNAT data]. / La femme de 40 ans et plus en FIV et en ICSI: données FIVNAT.

The proportion of women over 40 in i.v.f. and in i.c.s.i. has been dramatically increasing to reach 12% in 2002. Tubal and unexplained infertility increases with age. Short protocols or protocols with GnRH antagonists are more and more often used for older women. Best results are nevertheless still obtained with long protocols! Up to 35 years, pregnancy rates are similar with two or three transferred embryos. Over 35, better results are observed with three embryos. However, the rate of twins only falls below 20% when the woman is over 38, in i.v.f. as well as in i.c.s.i. The decreasing pregnancy rate should be better known by patients and clinicians so that women are treated sooner for i.v.f.

[Assisted Reproductive Technologies in HIV patients: a comprehensive review of indications, techniques and results]. / Assistance médicale à la procréation et VIH: revue des indications, techniques et résultats.

Assisted Reproductive Technologies (ART) are authorized in France in couples infected by the human immunodeficiency virus (HIV) since the French legislation of May 10th, 2001. The goals are to reduce the risk of viral transmission between partners and to treat an underlying infertility. The classical techniques are used: IUI, IVF or ICSI, but all of them must be done in specifically authorized laboratories. ART outcome is favourable when only the man is infected, but seems to be less favourable when the woman is infected. Management of pregnancy planning should first propose to women infected by HIV, self inseminations when possible, and if needed, a quick ART treatment as some studies showed ovarian function alterations in HIV women. When the man is infected, IUI would be first proposed. Thousands of HIV positive male partners have used ART in Europe and no contamination has been reported so far. Approximately half of couples with one or both partners infected can hope to have a child through the ART process.

[Induction of ovulation]. / L'induction de l'ovulation.

OBJECTIVES: To elaborate guidelines for the use of different treatment and different protocols for ovarian stimulation. SEARCHED STRATEGY: We searched for all publications which described randomised controlled trial evaluating different ovarian stimulation protocols and different indications on PubMed, Medline and Cochrane Database. The keywords were: ovulation induction, citrate of clomiphene, gonadotropin, metformin, anti estrogens, anti aromatase, pulsatile GnRH administration, cancer, ovarian hyperstimulation, thrombosis, multiple pregnancies, and complications. Randomised controlled trials were first considered. Then was considered recent meta analysis and cohort study. We mentioned when literature was weak.

Long-term outcome of distal ulna resection-stabilisation procedures in post-traumatic radio-ulnar joint disorders.

INTRODUCTION: Distal radius fractures represent 20% of fractures in adults. Although good results are usually obtained with treatment, functional sequelae are not uncommon, with injury of the distal radio-ulnar joint (DRUJ) being the most frequent. Various treatments have been described to address these disorders. Distal ulna resection-stabilisation (DURS) is our technique of choice when preservation of the DRUJ is impossible. PATIENTS AND METHOD: Twenty patients operated between 1985 and 1996 were reviewed with minimum 6-year follow-up. Nine of them were men and 11 were women, with an average age 45 years. The initial trauma was a distal radius fracture in all cases. The main complaint was ulnar pain with no limitation of mobility in five patients, painful limitation of prono-supination in 14, and palmar subluxation of the ulna in one case. Radiographic evaluation and CT scan showed DRUJ incongruence in 14 patients with ulna head instability, and ulno-carpal abutment with degenerative changes at the DRUJ in six cases. In three patients, malunion of the distal radius was associated with degenerative DRUJ lesions. RESULTS: The satisfaction rate was 95% at an average follow-up of 11 years (range 6.7 to 18.6 years). Pain scores decreased progressively from 2.2 to 0.5 post-operatively. Range of motion improved in supination from 37 degrees to 80 degrees , and in pronation from 66 degrees to 84 degrees . Improvements were 15 degrees in ulnar inclination, 9 degrees in radial inclination, 16 degrees in flexion, and 23 degrees in extension. Distal ulna palpation was not painful, and no instability was observed on movement. Wrist strength was equivalent to 80.8% of the healthy contra-lateral side. Radiographic results showed no anomaly of the resected ulna, no sign of abutment on the radius and no ulnar translation of the carpus at follow-up. Only one patient, who presented algoneurodystrophic syndrome after the initial trauma, had a recurrence after DURS. DISCUSSION-CONCLUSION: DRUJ injuries are frequent in the context of wrist trauma. If not well-treated, they could lead to significant functional sequelae of the wrist. Radiographic evaluation should clarify the status of the DRUJ to choose between conservative or radical surgical treatment. If the DRUJ surfaces are preserved, conservative treatment, which consists of correcting the distal radius malunion and stabilising or shortening the ulna, is the treatment of choice. When the DRUJ surfaces are injured, DURS is our treatment of choice. This approach presents a low complication rate and more than 90% of satisfactory results, often with a pain-free wrist, functional range of motion and good strength. However, a rigorous technique, with limited ulna head resection, dorsal capsuloplasty, reconstruction of the extensor retinaculum and dorsal placement of the extensor carpi ulnaris tendon, is a prerequisite for success. LEVEL OF EVIDENCE: Level IV retrospective therapeutic study.

[Institutional review board of the French college of obstetricians and gynecologists (CEROG).]. / Le Comité d'éthique de la recherche en obstétrique et gynécologie (CEROG).

OBJECTIVE: To report the rules and the activity of the institutional review board of the French college of obstetricians and gynecologists (Comité d'éthique de la recherche en obstétrique et gynécologie [CEROG]) created in 2008. The submission requirements are also described. METHODS: Retrospective study. RESULTS: The Ethical Review Committee [institutional review board of the French college of obstetricians and gynecologists (CNGOF)] CEROG have examined 65 project studies in 2008. The median number of submitted studies was 5.5 per month (IQR: 3.75-6.25). The origins of the submission were as follows: tertiary care university hospitals (n=63, 97 %), Inserm (n=1), INRA (n=1). Researches were found to be in conformity with the French laws and regulations, to conform to generally accepted scientific principles and medical research ethical standards in 44 cases (68 %). In 13 cases (20 %), the study has been forwarded to the Persons Protection Committee (PPC) since it concerned biomedical research or "usual care research" (soin courant). In six cases (9 %), the investigators have not responded to IRB suggestions. In two cases (3 %), the information form has been judged unsatisfactory. CONCLUSION: The CEROG is the first national IRB in obstetrics and gynecology. This new committee clarifies IRB submission procedure in France concerning non-interventional studies in the field of obstetrics and gynecology.

Acute elbow dislocation with arterial rupture. Analysis of nine cases.

UNLABELLED: Elbow dislocations are the most frequently encountered dislocations after shoulder dislocations. In their vast majority these injuries involve only the joint and carry a good prognosis. Close anatomic proximity to the joint of neurovascular structures put them at risk of concomitant injury but this occurrence remains, actually very rare. The objective of this study is to retrospectively analyze the results of nine cases of elbow dislocations with brachial artery complications and to propose coherent therapeutic guidelines derived from this experience. MATERIALS AND METHODS: From 1999 to 2004, 357 elbow dislocations were treated by the traumatology team at the Purpan University Hospital and 340 at the Rangueil University Hospital in Toulouse, France. These two teaching institutions combined their series, contributing to seven dislocations associated with a brachial artery partial rupture, resulting in ischemia. Between 2001 and 2006 at the Le Mans Regional Hospital Center, 138 dislocations of the elbow were treated, and included two cases involving rupture of the brachial artery. In all these institutions' emergency departments, elbow dislocations were mainly treated on an outpatient basis: closed reduction under ultra short-acting products general anesthesia, with stability evaluation followed by cast immobilization. In the rare instances of ischemia, the artery was repaired in concert with the vascular surgery team. All the nine cases had a similar treatment protocol and were submitted to an identical outcome evaluation method. The patients were all males with a mean age of 37.3 years (range, 18-58 years). The combined injury occurred at sports in two cases, because of a fall in three cases and as a result of a traffic accident in four cases. Ischemia was complete in three cases (no radial or ulnar pulse and devascularized hand). In the six other cases, the clinical presentation was subacute. An arteriogram was obtained in five cases after reduction of the dislocation, confirming the brachial axis disruption. Median and/or ulnar nerve injury was suspected in six patients. Only five elbows remained stable after reduction allowing plaster cast immobilization. In the other cases, dislocation recurrence or consequential residual varus/valgus laxity required external fixation or a cross-pinning fixation. An autologous vein, brachial artery bypass was performed in eight cases and an end-to-end anastomosis was carried out in one case. Revascularization was reestablished between 4 and 19 h after injury (mean 10.5 h). RESULTS: All the patients were seen at a minimum of 2 years' follow-up (mean of 4.3 years). On the basis of Mayo Clinic score, the results were considered excellent in three cases, good in four cases, and poor in two cases. No patients complained of elbow instability. The X-rays showed a reduced elbow in all cases and heterotopic ossifications in three cases. No degenerative lesion was observed at the longest follow-up. DISCUSSION: The incidence of a combined vascular injury with dislocation remains difficult to establish because the literature reports sporadic short series of clinical cases. The prevalence of this association is estimated to be between 0.3 and 1.7% in hospitals. The vascular lesion risk is probably related to the displacement extent and this later as a consequence of the injury intensity. This context calls for a diagnostic warning signal of possibly associated vascular involvement. Assessment of arterial vascularization should be systematic and mandatory with any osteoarticular injury. The slightest vascular status clinical doubt after reducing any dislocation presses for vascular patency work-up: echo-Doppler, angio-scan, arteriography. The multi-parametric nature of these combined injuries explain why their sometimes disappointing outcome remains dependent on the ability to deal with contradictory healing concerns: skin condition, capsular, and ligaments damages, type of revascularization procedure used, joint stability after closed reduction. This last parameter, being a substantial determinant for the period of immobilization, appears crucial to the final functional outcome, particularly in terms of range of motion loss or residual flexion contracture. LEVEL OF EVIDENCE: Level IV. Therapeutic retrospective study.