Top 10 priorities for future infertility research: an international consensus development study.

STUDY QUESTION: Can the priorities for future research in infertility be identified? SUMMARY ANSWER: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care for people with fertility problems were identified. WHAT IS KNOWN ALREADY: Many fundamental questions regarding the prevention, management, and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems. STUDY DESIGN, SIZE, DURATION: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines, and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, people with fertility problems, and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance. MAIN RESULTS AND THE ROLE OF CHANCE: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties were entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities, and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI, and IVF), and ethics, access, and organization of care, were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment, and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings, and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research, and population science. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgement, and arbitrary consensus definitions. WIDER IMPLICATIONS OF THE FINDINGS: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems, and others, will help research funding organizations and researchers to develop their future research agenda. STUDY FUNDING/ COMPETING INTEREST(S): The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand, and Maurice and Phyllis Paykel Trust. Geoffrey Adamson reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies, and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. Hans Evers reports being the Editor Emeritus of Human Reproduction. Andrew Horne reports research sponsorship from the Chief Scientist's Office, Ferring, Medical Research Council, National Institute for Health Research, and Wellbeing of Women and consultancy fees from Abbvie, Ferring, Nordic Pharma, and Roche Diagnostics. M. Louise Hull reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. Neil Johnson reports research sponsorship from Abb-Vie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics, and Vifor Pharma. José Knijnenburg reports research sponsorship from Ferring and Theramex. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Ernest Ng reports research sponsorship from Merck. Craig Niederberger reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. Jane Stewart reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring, and being a clinical subeditor of Human Fertility. Annika Strandell reports consultancy fees from Guerbet. Jack Wilkinson reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. Andy Vail reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from HFEA for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. Lan Vuong reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: Not applicable.

Top 10 priorities for future infertility research: an international consensus development study† ‡.

STUDY QUESTION: Can the priorities for future research in infertility be identified? SUMMARY ANSWER: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care for people with fertility problems were identified. WHAT IS KNOWN ALREADY: Many fundamental questions regarding the prevention, management and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems. STUDY DESIGN, SIZE, DURATION: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, people with fertility problems and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance. MAIN RESULTS AND THE ROLE OF CHANCE: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties was entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI and IVF) and ethics, access and organization of care were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research and population science. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgment and arbitrary consensus definitions. WIDER IMPLICATIONS OF THE FINDINGS: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems and others, will help research funding organizations and researchers to develop their future research agenda. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand and Maurice and Phyllis Paykel Trust. G.D.A. reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. A.W.H. reports research sponsorship from the Chief Scientist's Office, Ferring, Medical Research Council, National Institute for Health Research and Wellbeing of Women and consultancy fees from AbbVie, Ferring, Nordic Pharma and Roche Diagnostics. M.L.H. reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. N.P.J. reports research sponsorship from AbbVie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics and Vifor Pharma. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from AbbVie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. E.H.Y.N. reports research sponsorship from Merck. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring and retains a financial interest in NexHand. J.S. reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring and being a clinical subeditor of Human Fertility. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: N/A.

[Medical treatment of endometriosis: an obligation rather than a mere option!]. / Traitement médical de l'endométriose: pas une simple option, mais une obligation !

The aim of this article is to argue the usefulness of the systematic administration of medical treatment in women managed for endometriosis, either alone or associated with the surgery. The authors dispute seven frequent objections against the medical treatment: the lack of curative effect, the lack of primary prevention and the risk of delaying the diagnostic, the contraceptive effect in women wishing to conceive, the adverse effects, the risk of occurrence of new lesions following the arrest of the treatment, the lack of proof favourable to the efficient prevention of recurrences and the cost of the treatment. The authors conclude that to date the therapeutic amenorrhea represents an indispensable tool in the management of the endometriosis, in women both benefiting or not from surgical procedures.

Newborn's giant sacrococcigeal teratoma.

A sacrococcigeal tumor was detect at ultrasound maternal exam in 25TH week of pregnancy. The girl was born full term by natural way by the parents' choise. The newborn present a tumor with 12 cm diameter, situated in sacrococcigeal region, with a large base of implantation and with posteroinferior growth. This tumor produced a dislocation of the rectum and a perineal area. In the first day of baby's life, we perform the operation. We removed a large tumor (600 gr) with the coccys bone and we obtained a good repair of anatomy of the region, without postoperatory functional troubles. Postoperatory evolution was good. The newborn lived hospital healed in the 14th day. The histopatologic exam confirmed that the tumor was benign. Later evolution was good.

[Surgical treatment of tubo-ovarian abscess occurring in deep endometriosis]. / Prise en charge chirurgicale des abcès tubo-ovariens compliquant une endométriose profonde.

Tubo-ovarian abscesses are likely to occur in women suffering from deep endometriosis. The aim of surgical management of tubo-ovarian abscesses is the laparoscopic drainage, while deep endometriosis resection should be delayed. Laparoscopic procedure carried out in emergency does not attempt at the excision of deep endometriotic lesions, and must avoid the choice of the laparoconversion, in order to avoid further changes in the pelvic anatomy rendering more difficult a curative surgery. We report six cases of patients presenting tubo-ovarian abscesses arising on deep endometriosis, and we discuss the choice of the 2-step surgical management. In four cases, deep endometriosis resection has been performed by laparoscopic route few months after the drainage of abscess and provided macroscopically complete excision of the disease.

[Guidelines for the management of painful endometriosis]. / Tratamentul endometriozei dureroase. Recomandari pentru practica clinica.

OBJECTIVE: To establish guidelines for the medical and surgical management of painful endometriosis. MATERIAL AND METHODS: An exhaustive review on Medline and Cochrane Database between 1980 and 2006 was performed. RESULTS: GnRH agonists, progestins, continuous monophasic oral contraceptives and danazol have a suppressive effect on dysmenorrhoea, nonmenstrual pain and dyspareunia (grade A). Surgical treatment is effective in painful endometriosis (grade B). Complete surgical excision of deep endometriotic lesions with conservation of uterus and ovaries has a limited term efficacy on pain relief (grade C). A multidisciplinary approach is recommended (grade C). The use of the psychotherapy improves the management of chronic pain (grade A). There is a lack of information concerning the therapeutic strategy able to prevent recurrences. Whether endometriosis recurrences occur, medical treatment should be the first line approach (expert opinion). A hysterectomy with salpingo-oophorectomy and complete excision of the lesions is efficient in women with pain recurrence who no longer desire pregnancy (grade C). CONCLUSIONS: Medical and surgical treatments have a limited term efficacy on painful endometriosis (grade A). The benefit/risk ratio, depending on side-effects, should be assessed on a case to case basis.

[Management of menometrorrhagia in women with and without pregnancy intention: hierarchy of therapies]. / Hiérarchisation des stratégies thérapeutiques pour ménométrorragies avec ou sans désir de grossesse.

The first line of treatment recommended for women with idiopathic menorrhagia is pharmaceutical agents, i.e. levonorgestrel intra-uterine device, tranexamic acid, estroprogestatif pills, oral progestin and non-sterodial anti-inflammatory drugs. The second line of treatment is surgical, using endometrial curettage for women who desire pregnancy in the future. On the other hand, in women who no longer intend to get pregnant either endometrial ablation or hysterectomy can be used. The menorrhagia associated with endometrial polyps is treated through the hysteroscopic polypectomy, which result can be improved by the use of the levonorgestrel intra-uterine device or the endometrial ablation. The menorrhagia related to submucosal myomas is managed by hysteroscopic myomectomy, either as a first line of treatment or following the failure of the pharmaceutical management. The first line of treatment of interstitial myomas is represented by the medical management, followed by laparoscopic or abdominal myomectomy for women who still want to be pregnant, and by myomectomy or uterine arteries embolization for women who no longer desire pregnancy. Hysterectomy is the most efficient treatment of menorrhagia due to interstitial myomas, and may be proposed either as a third line of treatment for the myomectomy and embolization failures or as a second line of treatment for women who do not wish to conserve their uterus. Finally, the treatment for women with clinically or radiologically suspected adenomyosis is medical, followed by hysterectomy for women who desire no pregnancy.

[Laparoscopic surgery of profund endometriosis with rectal affect]. / Chirurgia laparoscopica a endometriozei profunde cu atingere rectala.

OBJECTIVE: To present the principles of laparoscopic treatment for rectal endometriosis and to discuss possible postoperative outcomes. MATERIAL AND METHODS: Our series included women managed for rectal endometriosis during consecutive 20 months in the Department of Gynecology and Obstetrics, Rouen University Hospital, Rouen--France. Patient's characteristics, symptoms, imaging examination results, surgical treatment and postoperative outcomes were all evaluated retrospectively. RESULTS: Sixteen patients presenting with rectal endometriosis were managed surgically, (mean age was 35.9 +/- 6.5 years). All women presented at least one severe painful symptom which was typical of a digestive involvement in 12 cases. MRI results suggested a rectal involvement in 14 cases, and endorectal ultrasound examination clearly showed rectal wall infiltration in all patients. The gynaecological stage of surgical treatment was carried out laparoscopically in 13 cases, and the digestive surgical stage in 7 cases. Two limited and 14 segmental rectal resections were performed. Transitory stoma was carried out in 9 women. The length of the surgical procedure depended on the number of endometriosis localizations with a median value of 6 h 30 min. Postoperative complications occurred in 6 women: 2 anastomosis stenosis, 1 anastomosis fistula, 1 abscess of the parietal wall and 1 bladder atonia. Complains of pain were completely or significantly improved in all cases. CONCLUSION: Surgical treatment for rectal endometriosis may be carried out laparoscopically. It should be reserved for women presenting with severe painful condition and may contribute to significant improvement. However, the balance of benefit and risks must also be assessed on a case to case basis prior to any decision for or against surgical treatment.