New expert advice on cancer in pregnancy.

Cancer in pregnancy is rare, and most physicians lack knowledge in handling pregnant cancer patients. This review summarises the present knowledge on this condition. In the Netherlands, an Advisory Board on Cancer in Pregnancy was established in 2012. The board supports Dutch physicians' decisions in the management of pregnant patients with cancer. In 2021 the International Advisory Board on Cancer in Pregnancy was established, and in continuation, the Danish Advisory Board on Cancer in Pregnancy (DABCIP) has now been founded. DABCIP consists of 22 members from 13 different medical disciplines.

Cryopreservation of ovarian tissue as fertility preservation in young women with multiple sclerosis before stem cell transplantation.

BACKGROUND: Women of fertile age who receive autologous hematopoietic stem cell transplantation (AHSCT) due to multiple sclerosis (MS) are at risk of loss of ovarian function and infertility because of the conditioning regimen with alkylating agents. OBJECTIVE: To present our data on fertility preservation by ovarian tissue cryopreservation (OTC) in young women with MS before AHSCT. METHODS: Retrospective, observational cohort study RESULTS: Eight women had OTC. After AHSCT four had premature ovarian insufficiency (POI), and two of these had autotransplantation of their cryopreserved ovarian tissue. Both women regained ovarian function, and a spontaneous pregnancy was achieved resulting in the delivery of a healthy baby. CONCLUSION: OTC preserves fertility in young women with MS at risk of POI.

Fresh and cryopreserved ovarian tissue transplantation for preserving reproductive and endocrine function: a systematic review and individual patient data meta-analysis.

BACKGROUND: Ovarian tissue cryopreservation involves freezing and storing of surgically retrieved ovarian tissue in liquid or vapour nitrogen below -190°C. The tissue can be thawed and transplanted back with the aim of restoring fertility or ovarian endocrine function. The techniques for human ovarian tissue freezing and transplantation have evolved over the last 20 years, particularly in the context of fertility preservation in pre-pubertal cancer patients. Fresh ovarian tissue transplantation, using an autograft or donor tissue, is a more recent development; it has the potential to preserve fertility and hormonal function in women who have their ovaries removed for benign gynaecological conditions. The techniques of ovarian tissue cryopreservation and transplantation have progressed rapidly since inception; however, the evidence on the success of this intervention is largely based on case reports and case series. OBJECTIVE AND RATIONALE: The aim of this study was to systematically review the current evidence by incorporating study-level and individual patient-level meta-analyses of women who received ovarian transplants, including frozen-thawed transplant, fresh or donor graft. SEARCH METHODS: The review protocol was registered with PROSPERO (CRD42018115233). A comprehensive literature search was performed using MEDLINE, EMBASE, CINAHL and Cochrane Central Register of Controlled Trials from database inception to October 2020. Authors were also contacted for individual patient data if relevant outcomes were not reported in the published manuscripts. Meta-analysis was performed using inverse-variance weighting to calculate summary estimates using a fixed-effects model. OUTCOMES: The review included 87 studies (735 women). Twenty studies reported on ≥5 cases of ovarian transplants and were included in the meta-analysis (568 women). Fertility outcomes included pregnancy, live birth and miscarriage rates, and endocrine outcomes included oestrogen, FSH and LH levels. The pooled rates were 37% (95% CI: 32-43%) for pregnancy, 28% (95% CI: 24-34%) for live birth and 37% (95% CI: 30-46%) for miscarriage following frozen ovarian tissue transplantation. Pooled mean for pre-transplant oestrogen was 101.6 pmol/l (95% CI: 47.9-155.3), which increased post-transplant to 522.4 pmol/l (95% CI: 315.4-729; mean difference: 228.24; 95% CI: 180.5-276). Pooled mean of pre-transplant FSH was 66.4 IU/l (95% CI: 52.8-84), which decreased post-transplant to 14.1 IU/l (95% CI: 10.9-17.3; mean difference 61.8; 95% CI: 57-66.6). The median time to return of FSH to a value <25 IU/l was 19 weeks (interquartile range: 15-26 weeks; range: 0.4-208 weeks). The median duration of graft function was 2.5 years (interquartile range: 1.4-3.4 years; range: 0.7-5 years). The analysis demonstrated that ovarian tissue cryopreservation and transplantation could restore reproductive and hormonal functions in women. Further studies with larger samples of well-characterized populations are required to define the optimal retrieval, cryopreservation and transplantation processes. WIDER IMPLICATIONS: Ovarian tissue cryopreservation and transplantation may not only be effective in restoring fertility but also the return of reproductive endocrine function. Although this technology was developed as a fertility preservation option, it may have the scope to be considered for endocrine function preservation.

[Fertility preservation].

Fertility preservation should be considered in girls and young women faced with a potentially gonadotoxic treatment such as chemotherapy. IVF can be performed with the aim to collect and freeze the oocytes, or ovarian tissue can be cryopreserved and transplanted back to the patient at a later stage. Whichever method is chosen depends upon the age of the patient, the gonadotoxicity of her treatment and the time frame. It is important to refer young cancer patients to fertility preservation counselling before treatment starts, as argued in this review.

[Fertility counselling of younger women after cancer treatment].

Girls and younger women of fertile age are at risk of infertility and premature ovarian insufficiency, if they have received chemotherapy or radiotherapy. While many are offered fertility preservation before treatment, many are left with a need for follow-up after treatment, which is pointed out in this review. At the fertility clinic at Rigshospitalet, Denmark, a follow-up clinic has been introduced for previous cancer patients with focus on reproductive health, including assessment of ovarian function, planning of future pregnancies and initiation of hormone replacement therapy if needed.

Quantitative Differences in TGF-ß Family Members Measured in Small Antral Follicle Fluids From Women With or Without PCO.

CONTEXT: Members of the TGF-ß family have been implicated in aberrant follicle development in women with polycystic ovaries (PCO). OBJECTIVE: Are there quantitative differences in the concentrations of TGF-ß family members in fluid from human small antral follicles (hSAFs) in women with or without PCO? DESIGN AND SETTING: Follicle fluids (FFs) were collected from 4- to 11-mm hSAFs obtained from women undergoing ovarian tissue cryopreservation for fertility preservation. PATIENTS: FFs from 16 women with PCO (FF = 93) and 33 women without PCO (FF = 92). MAIN OUTCOME MEASURES: Intrafollicular concentrations of growth differentiation factor-9 (GDF9); anti-Müllerian hormone (AMH); inhibin-A and inhibin-B; total inhibin; activin-A, activin-B, and activin-AB; follistatin; follistatin-like-3; estradiol; and testosterone. RESULTS: Activin-B concentrations were reported in hSAFs, and concentrations were 10 times higher than activin-A and activin-AB concentrations. Activin-B showed significant associations with other growth factors. Concentrations of inhibin-A and inhibin-B were significantly lower in FFs from women with PCO, especially in hSAFs <8 mm in diameter. AMH concentrations did not differ between the groups in hSAFs <8 mm; however, AMH remained high in hSAFs >8 mm in women with PCO but decreased in women without PCO. Estradiol was significantly lower in FFs from women with PCO and showed significant associations with AMH. Concentrations of GDF9 showed significantly higher concentrations in PCO FFs of follicles >6 mm. CONCLUSIONS: Altered concentrations of TGF-ß family members in hSAFs from women with PCO highlight altered growth factor signaling as a potential mechanism for follicle growth arrest.

Retinal artery and vein diameters during pregnancy in diabetic women.

PURPOSE: To study systemic and retinal circulatory variables and vasoactive hormones during pregnancy in women with and without diabetes. METHODS: Prospective study of 45 women with type 1 diabetes and 6 healthy pregnant women, from the first trimester of pregnancy to half a year after delivery, by using a fundus photographic method of determining retinal vessel diameters. RESULTS: In diabetic women, the mean arterial blood pressure increased from 90.7 +/- 10.9 mm Hg (mean +/- SD) in the first trimester to 102.4 +/- 16.4 mm Hg in the third trimester, accompanied by retinal arteriolar constriction, from a mean diameter of 95.5 +/- 11.3 to 92.2 +/- 12.9 microm (P = 0.007), arteriolar constriction being prominent in nonsmokers, from 96.6 +/- 11.1 to 92.3 +/- 13.0 microm (P < 0.001; n = 38), but absent in smokers, from 89.2 +/- 11.5 to 92.0 +/- 13.6 microm (P = 0.28). Healthy nonsmoking women demonstrated an increase in blood pressure during pregnancy comparable to that in diabetic women, but the change in mean retinal arteriolar diameter, from 88.5 +/- 10.9 microm in the first to 91.6 +/- 10.2 microm in the third trimester, did not reach statistical significance (P = 0.38). Diabetic retinopathy levels increased during pregnancy, but the change in arteriolar diameter from the first to the third trimester did not correlate with retinopathy, arterial blood pressure, HbA(1c), or atrial natriuretic peptide. Plasma angiotensin II correlated positively with the change in arteriolar diameter in women who did not smoke (P < 0.05). After delivery, retinal vessel diameters returned to the first trimester range in all subgroups. CONCLUSIONS: From the first to the third trimester of pregnancy, blood pressure increased and retinal arteriolar diameter decreased in diabetic women, but the arteriolar constriction associated with pregnancy and systemic arterial blood pressure increase was remarkably absent in diabetic women who smoked tobacco before and during pregnancy. It is unknown whether smoking inhibits this vasoconstrictive response by deactivating mechanisms of physiological adaptation or by activating these mechanisms before the first trimester of pregnancy.