Endometriosis is a common finding among women with infertility, and women who are diagnosed with endometriosis are almost twice as likely to experience infertility. Mechanisms by which endometriosis causes infertility remain poorly understood. In this review, we evaluate the current literature on the impact of endometriosis on oocyte and embryo quality. The presence of endometriosis evidently reduces ovarian reserve, oocyte quality, and embryo quality; however, this does not appear to translate to a clear clinical impact. Analysis of data from large assisted reproduction technology registries has shown that women with endometriosis have a lower oocyte yield but no reduction in reproductive outcomes. There is a need for future studies in the form of well-designed randomized controlled trials to further evaluate the role of surgical and medical treatment options in women with endometriosis undergoing assisted conception.

In vitro fertilization (IVF) is an established option for the management of infertility in patients with endometriosis, though there remains ongoing debate around the extent to which endometriosis may compromise IVF treatment success, in which fertilization and preimplantation embryo development occur outside the pelvis. Whether endometriosis impacts oocyte and embryo quality and/or endometrial receptivity remains central to this debate. Here, we review the current literature relating to the impact of endometriosis on IVF outcomes and management strategies to consider when performing IVF treatment.

Adenomyosis can reduce the chance of clinical pregnancy in women undergoing assisted conception. Treatment with prolonged gonadotrophin-releasing hormone analogue (GnRHa) downregulation prior to IVF/ICSI has been postulated to improve pregnancy outcomes. We aimed to evaluate the effectiveness and safety of prolonged GnRHa treatment (minimum one month) versus no pre-treatment in women with adenomyosis undergoing IVF/ICSI using a systematic review and meta-analysis. We searched electronic databases: Embase (OVID), MEDLINE® (OVID), APA PsycInfo (OVID), Maternity & Infant Care Database (MIDIRS (OVID), HMIC Health Management Information Consortium (OVID) and ClinicalTrials.gov from inception until 27th of March 2023. We included studies that reported on women with adenomyosis receiving GnRHa to down-regulate the hypothalamic-pituitary-ovarian axis for one to six months before IVF/ICSI. We pooled data using the Haensel-Mantel method and reported using Odds Ratio (OR) with 95 % confidence intervals (CI). We assessed the quality of included studies using the Newcastle-Ottowa Scale and confidence in evidence using the GRADE criteria. Bias analysis was conducted via the Cochrane recommended tool (RevMan Web, Academic License). We screened 365 citations and eight retrospective studies were included in the meta-analysis (n = 2422 women). The median age was 34 years [IQR 31.95-35.05], median BMI 21.30 kg/m² [IQR 21.05-23.55] and median duration of GnRHa downregulation was 2.5 months [Range 1-4; IQR 1.37-3]. Women with adenomyosis receiving prolonged GnRHa treatment had a higher implantation rate 1/OR 1.69 [95 % CI 1.09, 2.56], I² = 81 %, (P = 0.02) and clinical pregnancy rate 1/OR 1.42 [95 % CI 1.03, 2.0], I² 70 %, P = 0.03. There was no overall difference in live birth rate 1/OR 1.12 [95 % CI 0.70, 1.79], I² = 78 %, p = 0.63), miscarriage rate 1/OR 0.92 [95 % CI 0.63, 1.28, P = 0.61, I² 0 % or mean number of oocytes retrieved (10 oocytes [IQR 8.95; 11.15] vs. 9.28 [IQR 8; 10.20], p = 0.22) between groups. The benefit of prolonged GnRHa treatment in women with adenomyosis undergoing assisted conception treatment is uncertain based on existing retrospective studies. Implantation and clinical pregnancy rates were higher following prolonged downregulation in this population, though there was no statistically significant difference in live birth and miscarriage rates. Given the limited, low-quality existing data, there is a need for a well-designed, prospective randomised controlled trial to precisely evaluate the effectiveness of prolonged GnRHa treatment in this population.

STUDY QUESTION: What are the clinical and ethical challenges of performing ovarian stimulation and oocyte cryopreservation in adolescents and the barriers to providing treatment? SUMMARY ANSWER: Our study shows that, in one of the largest case series to date in this population, post-pubertal adolescents as young as age 13 years can undergo ovarian stimulation and oocyte cryopreservation with a response comparable to adults. WHAT IS KNOWN ALREADY: Fertility preservation in adolescents has not been well studied, with little data available in the existing literature. Referrals for fertility preservation in adolescents are increasing due to developments in childhood cancer treatments, which have led to a growing population of children at risk of developing premature ovarian insufficiency. Those with certain benign conditions or gender incongruence also face this challenge. All established fertility preservation guidelines state that where there is a risk to fertility, oocyte cryopreservation should be offered to post-pubertal females. However, counselling and consenting young people about fertility decisions is an ethically complex area, and assessing capacity to consent in this age group is not straightforward. STUDY DESIGN, SIZE, DURATION: This was a retrospective observational cohort study of 182 referrals for fertility preservation counselling to a specialist unit, and we present outcomes for the 33 adolescents who underwent 36 cycles of ovarian stimulation and oocyte cryopreservation between January 2018 and January 2024. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included patients aged 13–18 years who underwent ovarian stimulation and oocyte cryopreservation for fertility preservation due to high or intermediate risk of gonadotoxicity from medical or surgical treatment at a public-funded specialist unit. The primary outcome was oocyte yield; secondary outcomes included oocyte maturity rate, complications, and dropout rate. Data were retrieved from a prospectively managed database. MAIN RESULTS AND THE ROLE OF CHANCE: There was a total of 182 referrals received, and of these, 33 patients underwent 36 cycles of ovarian stimulation and oocyte cryopreservation. Indications for fertility preservation included malignancy n = 19/36 (54%), ovarian cyst surgery n = 7/36 (19%), immunological disorders n = 4/36 (11%), benign haematological disease n = 2/36 (6%), gender reassignment treatment n = 3/36 (8%), and genetic conditions n = 1/36 (3%). The youngest child who underwent ovarian stimulation was aged 13 years and 10 months at the time of egg collection; the minimum time from menarche to ovarian stimulation was 4 months, the median AMH (anti-Müllerian hormone) was 16.7 pmol/l (range 2.8–36.9 pmol/l), and the antral follicle count (AFC) was 11 (3–36). The median number of cryopreserved oocytes was 14 (range 4–39), and the oocyte maturity rate was 85% (35–100%). Ultrasound monitoring was performed transabdominally in 5/33 (15%) and transvaginally in 28/33 (85%). Egg collection was performed transvaginally in all cases in this cohort. All cycles proceeded to completion. All adolescents were counselled in association with a family member to obtain informed consent, and all were assessed as able to comprehend discussions. LIMITATIONS, REASONS FOR CAUTION: In view of concerns regarding increased aneuploidy rates in this age group compared to women in their twenties, there is a need for long-term outcome studies expanding on our findings with data on livebirths to support clinicians needing to counsel patients and perform oocyte cryopreservation in adolescents. WIDER IMPLICATIONS OF THE FINDINGS: Clinician experience, correct setting, and availability of funding will enable a permissive environment for oocyte cryopreservation in adolescents. In our experience, transvaginal egg collection is an accepted procedure when counselled appropriately. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this work. No competing interests are declared. TRIAL REGISTRATION NUMBER: N/A.

Fertility preservation has gained momentum in recent years. As cancer survival rates improve, late effects of loss of gonadal function have increased the need to consider fertility preservation. NICE recommends offering cryopreservation of gametes or embryos to patients undergoing gonadotoxic therapy, highlighting that this should be extrapolated to those with non-malignant conditions that pose a risk to fertility. We investigated whether variation in fertility preservation provision exists across the United Kingdom, with a view to identifying equitable models of provision. In England, cryopreservation of gametes and embryos is funded for all patients undergoing treatment for cancer, but eligibility criteria and duration of storage funding vary widely. In Scotland, a national policy is applied, with health boards equitably providing funding for cryopreservation of gametes, embryos, and ovarian and testicular tissue for those undergoing treatment for benign and malignant conditions which impair fertility, including gender incongruence. In Wales and Northern Ireland, cryopreservation of gametes and embryos is funded for those undergoing treatment likely to make them infertile, but ovarian tissue cryopreservation is not funded. Funding criteria for fertility preservation in England, Wales, and Northern Ireland deviates from NICE guidance. Standardization of fertility preservation policies is needed to provide equity of access for patients.

Endometriosis is a common finding among women with infertility and women who are diag-nosed with endometriosis are almost twice as likely to experience infertility. Mechanisms by which endometriosis causes infertility remain poorly understood. In this review we evaluate the current literature on the impact of endometriosis on oocyte and embryo quality. The presence of endometriosis evidently reduces ovarian reserve, oocyte quality and embryo quality, however this does not appear to translate to a clear clinical impact. Analysis of data from large assisted reproduction technology registries has shown that women with endometriosis have a lower oo-cyte yield but no reduction in reproductive outcomes. There is a need for future studies in the form of well-designed randomised controlled trials to further evaluate the role of surgical and medi-cal treatment options in women with endometriosis undergoing assisted conception.