Gynaecologists' view on diagnostic delay and care performance in endometriosis in the Netherlands.

RESEARCH QUESTION: To evaluate implementation of the key recommendations of the European Society of Human Reproduction and Embryology (ESHRE) guidelines on endometriosis, and to assess factors influencing diagnostic delay of endometriosis from Dutch gynaecologists' point of view. DESIGN: Questionnaire study among gynaecologists from all hospitals in the Netherlands. The questionnaire consisted of 56 questions relating to implementation of the ESHRE guidelines, organization of endometriosis care and diagnostic delay. RESULTS: Gynaecologists from 67 out of 85 hospitals completed the questionnaire. A total of 99-100% of respondents agree with, and 91-100% adhere to, the diagnosis-related recommendations in the guidelines. Diagnostic delay is estimated at 42 months. Main factors contributing to diagnostic delay according to gynaecologists are lack of knowledge and awareness of endometriosis in both patients and medical professionals, as well as limitations in diagnostics and late referral. Suggested interventions to reduce diagnostic delay are aimed at improving knowledge and awareness in both patients and medical professionals, as well as improving collaborations between medical professionals. CONCLUSIONS: Overall familiarity with, and use of, the 2014 ESHRE guidelines among Dutch gynaecologists is high. Dutch gynaecologists agree with the recommendations relating to diagnosis and adhere to them closely. Diagnostic delay, however, is still considerable; therefore, efforts to reduce diagnostic delay of endometriosis should be aimed at improving knowledge and awareness in both patients and medical professionals, as well as improving collaboration.

Klinefelter syndrome and fertility: sperm preservation should not be offered to children with Klinefelter syndrome.

STUDY QUESTION: Should fertility preservation be offered to children with Klinefelter syndrome (KS)? SUMMARY ANSWER: Current evidence shows that fertility preservation should not be offered to adolescents with KS younger than 16 years because of lower retrieval rates for germ cells by testicular sperm extraction (TESE) compared with retrieval rates for adolescents and adults between 16 and 30 years. WHAT IS KNOWN ALREADY: KS, the most common chromosomal disorder in men leading to non-obstructive azoospermia, is caused by the presence of at least one additional X chromosome. The onset of puberty in adolescents with KS leads to progressive degeneration of the testicular environment. The impact of the subsequent tissue degeneration on fertility potential of patients with KS is unknown, but in previous literature it has been suggested that fertility preservation should be started in adolescents as early as possible. However spermatozoa can be found by TESE in about 50% of adults with KS despite severe testicular degeneration. This review discusses the current evidence for fertility preservation in children and adolescents and possible prognostic markers for fertility treatment in KS. STUDY DESIGN, SIZE, DURATION: An extensive literature search was conducted, searching Pubmed, Embase, Cinahl and Web of Science from origin until April 2016 for 'Klinefelter syndrome' and 'fertility' and various synonyms. Titles and abstracts have been scanned manually by the authors for eligibility. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total 76 studies were found to be eligible for inclusion in this review. Information from the papers was extracted separately by two authors. MAIN RESULTS AND THE ROLE OF CHANCE: Various studies have shown that pre-pubertal children with KS already have a reduced number of germ cells despite a normal hormonal profile during childhood. The presence of spermatozoa in the ejaculate of adolescents with KS is extremely rare. Using TESE, the retrieval rates of spermatozoa for adolescents younger than 16 years old are much lower (0-20%) compared with those for adolescents and young adults between 16 and 30 years old (40-70%). Although spermatogonia can be found by TESE in about half of the peri-pubertal adolescents, there are currently no clinically functional techniques for their future use. Children and adolescents need to be informed that early fertility preservation before the age of 16 cannot guarantee fertility later in life and may even reduce the chances for offspring by removing functional immature germ cells which may possibly develop into spermatozoa after puberty. Furthermore, except for the age of patients with KS, there are no identified factors that can reliably be used as a predictive marker for fertility preservation. LIMITATIONS, REASONS FOR CAUTION: Most of the evidence presented in this review is based on studies including a small number of adolescents with KS. Therefore, the studies may have been underpowered to detect clinically significant differences for their various outcomes, especially for potential predictive factors for fertility preservation, such as hormone levels. Furthermore, the population of patients with KS diagnosed during childhood might be different from the adult population with KS where the diagnosis is based on infertility. Results based on comparisons between the two groups must be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: Despite the limitations, this review summarizes the current evidence for managing fertility preservation in patients with KS to provide optimal health care. STUDY FUNDING/COMPETING INTERESTS: There was no funding for this study. S.F., Y.H., K.D., W.L.M.N., D.S., H.L.C.-v.d.G. and L.R. declare to have no conflicts of interests. D.D.M.B. reports grants from Merck Serono, grants from Ferring and grants from MSD, outside the submitted work. K.F. reports personal fees from MSD (commercial sponsor), personal fees from Ferring (commercial sponsor), grants from Merck-Serono (commercial sponsor), grants from Ferring (commercial sponsor) and grants from MSD (commercial sponsor), outside the submitted work.