Reproductive and Endocrine Outcomes in a Cohort of Danish Women following Auto-Transplantation of Frozen/Thawed Ovarian Tissue from a Single Center.

Ovarian tissue cryopreservation (OTC) is a method of fertility preservation in girls and young women prior to gonadotoxic treatment. It is a safe and promising method to restore fertility. The initial recovery of endocrine function is high, but the longevity of the grafted tissue varies. In this single-center, combined retro- and prospective cohort study, we report the reproductive outcome and hormonal recovery following ovarian tissue transplantation (OTT) and evaluate possible predictors of the chance of pregnancy. The study includes 40 women from eastern Denmark undergoing 53 OTTs between 2003 and 2021. Permission to obtain retrospective data was given by the Danish Patient Safety Authorities and prospective data-collection by informed consent. Initial recovery of endocrine function was seen in 18/19 women with POI, and ongoing function of the grafted tissue in 7/14 two years from OTT. Live birth rate (LBR) was 41%, with 20 children to 39 women trying to conceive. Women who conceived had higher AFC at the time of OTC than women who did not (p ± 0.04). Repeated transplantations were not successful in terms of delivery. Half of all pregnancies were achieved by ART, but PRs were lower after ART than by spontaneous conception. LBRs after OTT are encouraging. Chance of pregnancy after OTT is correlated to ovarian reserve at OTC. Repeated transplantations were not successful in terms of unfulfilled pregnancy wish.

The Fertility Assessment and Counseling Clinic - does the concept work? A prospective 2-year follow-up study of 519 women.

INTRODUCTION: The Fertility Assessment and Counseling (FAC) Clinic was initiated to provide women with information about their current fertility status to prevent infertility and smaller families than desired. The aim was to study the predictive value of a risk assessment score based on known fertility risk factors in terms of time to pregnancy. MATERIAL AND METHODS: Prospective cohort study of the first 570 women attending the FAC Clinic from 2011 to 2013 at Rigshospitalet, Denmark. A consultation included: risk assessment score sheet with items on infertility risk factors, anti-Müllerian hormone and ultrasound. The risk score was categorized as low, medium or high. After 2 years an email-based questionnaire was distributed regarding subsequent pregnancies. RESULTS: The follow-up questionnaire was answered by 519 women (91.1%). The mean age was 35 years and 38% were single at inclusion. The majority (67.8%, 352/519) tried to conceive within 2 years after attending the FAC Clinic. At follow up, 73.6% (259/352) had achieved a pregnancy, 21% (74/352) were still trying and 5.4% (19/352) had given up. Two-thirds (65%) with only low risk scores conceived spontaneously within 12 months, although this figure was only 32% for women with at least one high risk score (n = 82). Accordingly, presence of at least one high risk score reduced the odds of achieving a pregnancy within 12 months by 75% (OR 0.25, 95% CI 0.12-0.52). CONCLUSION: The new FAC Clinic concept seems usable and offers a tool for fertility experts to guide women on how to fulfill their reproductive life-plan.

Immunologic Abnormalities, Treatments, and Recurrent Pregnancy Loss: What Is Real and What Is Not?

Recurrent pregnancy loss, depending on the definition, affects 1% to 3% of women aiming to have a child. Little is known about the direct causes of recurrent pregnancy loss, and the condition is considered to have a multifactorial and complex pathogenesis. The aim of this review was to summarize the evaluation and the management of the condition with specific emphasis on immunologic biomarkers identified as risk factors as well as current immunologic treatment options. The review also highlights and discusses areas in need of further research.

Individual fertility assessment and pro-fertility counselling; should this be offered to women and men of reproductive age?

During the 1970s new contraceptive options developed and legal abortions became accessible. Family planning clinics targeting young women and men provided advice and assistance on contraception. Today, delayed childbearing, low total fertility rates and increasing use of social oocyte freezing create a need for pro-fertility initiatives. Three years ago we established a new separate unit: The Fertility Assessment and Counselling (FAC) clinic. The FAC clinic offers free individual counselling based on a clinical assessment including measurement of serum anti-Müllerian hormone and ovarian and pelvic sonography in women, sperm analysis in men, and a review of reproductive risk factors in both sexes. The FAC clinic includes a research programme with the goal to improve prediction and protection of fertility. Our first proposition is that clinics for individual assessment and counselling need to be established, as there is a strong unmet demand among women and men to obtain: (i) knowledge of fertility status, (ii) knowledge of reproductive lifespan (women) and (iii) pro-fertility advice. Addressing these issues is often more challenging than treating infertile patients. Therefore, we propose that fertility assessment and counselling should be developed by specialists in reproductive medicine. There are two main areas of concern: As our current knowledge on reproductive risk factors is primarily based on data from infertile patients, the first concern is how precisely we are able to forecast future reproductive problems. Predictive parameters from infertile couples, such as duration of infertility, are not applicable, diagnostic factors like tubal patency are unavailable and other parameters may be unsuitable when applied to the general population. Therefore, strict validation of reproductive forecasting in women and men from the general population is crucial. The second main concern is that we may turn clients into patients. Screening including reproductive forecasting may induce unnecessary anxiety through false positive predictions and may even result in overtreatment in contrast to the intended preventive concept. False negative findings may create false reassurance and result in postponement of conceptions.

Perinatal outcomes in 375 children born after oocyte donation: a Danish national cohort study.

OBJECTIVE: To describe perinatal outcomes in children born after oocyte donation (OD) compared with in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and spontaneous conception (SC). DESIGN: National cohort study. SETTING: Fertility clinics. PATIENT(S): Three hundred seventy-five children born after OD during the period 1995-2010. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Mean birth weight, mean gestational age, risks of low birth weight (LBW), preterm birth (PTB), congenital malformations, cesarean delivery, preeclampsia, and admittance to neonatal intensive care unit. RESULT(S): We found an increased risk of PTB in OD pregnancies. The adjusted odds ratio (AOR) of PTB in OD singletons was 1.8 (95% CI, 1.2-2.69), 2.5 (95% CI, 1.7-3.6), and 3.4 (95% CI, 2.3-4.9) compared with IVF, ICSI, and SC, respectively. The risk of LBW was also increased. The AOR of LBW was 1.4 (95% CI, 0.9-2.2), 1.8 (95% CI, 1.2-2.8), and 2.6 (95% CI, 1.7-4.0) compared with IVF, ICSI, and SC. The risk of preeclampsia was increased in OD pregnancies with an AOR of 2.9 (95% CI, 1.8-4.6), 2.8 (95% CI, 1.7-4.5), and 3.1 (95% CI, 1.9-4.9) compared with IVF, ICSI, and SC. After additional adjustment for preeclampsia, perinatal outcome improved. Among the twins, the difference between the groups was less pronounced. CONCLUSION(S): Pregnancies after OD have a poorer perinatal outcome than those after standard IVF and ICSI mainly because of the high prevalence of preeclampsia.

Maternal homozygocity for a 14 base pair insertion in exon 8 of the HLA-G gene and carriage of HLA class II alleles restricting HY immunity predispose to unexplained secondary recurrent miscarriage and low birth weight in children born to these patients.

Homozygous carriage of a 14 base pair (bp) insertion in exon 8 of the HLA-G gene may be associated with low levels of soluble HLA-G and recurrent miscarriage (RM). We investigated the G14bp insertion(ins)/deletion(del) polymorphism in 339 women with unexplained RM and 125 control women. In all patients and patients with secondary RM after a firstborn boy, 19.2% and 23.9%, respectively, were G14bp ins/ins compared with 11.2% of controls (p<0.05 and p<0.01). Among secondary RM patients with a firstborn boy, G14bp del/del and no carriage of an HLA class II (HYrHLA) allele restricting immunity against male-specific minor HY antigens was found less often than in controls (p<0.05) whereas G14bp ins/ins and carriage of HYrHLA predisposed (p<0.08) to this clinical entity. The mean birth weight of firstborn boys born to G14bp ins positive secondary RM patients was significantly lower than expected (p<0.001) but only in carriers of HYrHLA alleles (p<0.01). In conclusion, homozygosity for G14bp ins predisposes to RM. The combination of G14 ins homozygosity and carriage of HYrHLA predisposes to secondary RM in women with a firstborn boy and negatively affects birth weight in these boys.

Acupuncture on the day of embryo transfer: a randomized controlled trial of 635 patients.

This prospective, randomized, controlled and double-blinded trial studied whether acupuncture in relation to embryo transfer could increase the ongoing pregnancy rates and live birth rates in women undergoing assisted reproductive therapy. A total of 635 patients undergoing IVF or intracytoplasmic sperm injection (ICSI) were included. In 314 patients, embryo transfer was accompanied by acupuncture according to the principles of traditional Chinese medicine. In the control group, 321 patients received placebo acupuncture using a validated placebo needle. In the acupuncture group and the placebo group, the ongoing pregnancy rates were 27% (95% CI 22-32) and 32% (95% CI 27-37), respectively. Live birth rates were 25% (95% CI 20-30) in the acupuncture group and 30% (95% CI 25-30) in the placebo group. The differences were not statistically significant. These results suggest that acupuncture administered in relation to embryo transfer has no effect on the outcome of IVF and ICSI.

Postpartum pelvic pain--the "pelvic joint syndrome": a follow-up study with special reference to diagnostic methods.

BACKGROUND: The etiology of pelvic joint syndrome (PJS) is not fully clarified. As a consequence, there is a lack of diagnostic methods to confirm the diagnosis, which today is mainly based on medical history. OBJECTIVE: The aim of this study was to examine women with PJS using various diagnostic methods. The hypothesis is that there are characteristics in this group of women that separate them from women who only suffer from pelvic pain during pregnancy and shortly after delivery, or healthy women. METHODS: Fifty-eight women participated in this follow-up study--twenty-one with PJS, 17 women who suffered from pelvic pain during pregnancy and shortly after delivery, and 20 controls with no history of pregnancy-induced pelvic pain. Clinical examination, gynecologic examination, psychological tests, spine X-ray, magnetic resonance imaging (MRI), blood samples, and urine dipsticks were performed. RESULTS: Clinical examination showed significant differences with regard to provocative tests and tenderness in the muscles and ligaments in the low back and the pelvis. Furthermore, psychological testing showed bad coping strategies when women with PJS were compared with those of the two control groups. However, no diagnostic method could explicitly differentiate between women with PJS and those of the two control groups. Thus, there was no significant difference in MRI, X-ray, blood or urine sample analysis. CONCLUSIONS: Women with PJS have positive provocative tests and ligament and muscular tenderness. Bad coping strategies might be an explanation why these women develop PJS.

Radiotherapy at a young age reduces uterine volume of childhood cancer survivors.

BACKGROUND: In contrast to chemotherapy, previous irradiation of the uterus carries an increased risk of an adverse pregnancy outcome. Conflicting results exist as regards the ability of the uterus to increase in volume following radiotherapy-induced damage. We measured uterine volume in a cohort of childhood cancer survivors, and assessed uterine response to a high-dose estrogen replacement regimen. METHODS: Uterine volume was assessed by transvaginal sonography in 100 childhood cancer survivors. Three patients with ovarian failure and severely reduced uterine volume following abdominal or pelvic irradiation were treated with percutaneous estradiol 150 microg/24 h for three cycles, and transvaginal uterine sonography was repeated monthly. RESULTS: Uterine volume was significantly reduced in nulliparous patients who had received direct uterine irradiation (n = 13; median 13 mL, range 1-52 mL) compared with nulliparous patients who had received chemotherapy only (n = 37; 47 mL, 22-88), radiotherapy above the diaphragm (n = 17; 40 mL, 24-61), or radiotherapy below the diaphragm not directly involving the uterus (n = 13; 34 mL, 8-77) (p < 0.02 in all comparisons). Among nulliparous patients a significant correlation was found between age at direct uterine irradiation and uterine volume (r = 0.78, p = 0.002). No significant improvement in uterine volume, endometrial thickness or uterine artery blood flow was observed in three hypogonadal patients in response to high-dose estrogen replacement therapy. CONCLUSIONS: Our results indicate that cytotoxic treatment in childhood does not affect adult uterine size. In contrast, uterine irradiation at a young age reduces adult uterine volume. The radiotherapy-induced damage is probably irreversible.

Reduced ovarian function in long-term survivors of radiation- and chemotherapy-treated childhood cancer.

Seventy percent of children with cancer survive. Radiation and chemotherapy may, however, impair ovarian function. The aim of this population-based study was to achieve a comprehensive knowledge of the degree of ovarian damage. Ovarian function was evaluated in 100 childhood cancer survivors and 21 controls of similar age. Menstrual cycle pattern was recorded, and strictly timed ovarian sonography and hormonal assessment were performed. The median age of the survivors was 5.4 yr (range, 0.1-15.3) at the time of diagnosis and 25.7 yr (18.5-44.4) at study entry. Seventeen survivors with premature ovarian failure had follicle-depleted or nondetectable ovaries, elevated FSH and LH, and immeasurable inhibin B. Thirteen survivors used oral contraception. Survivors with spontaneous menstrual cycles (n = 70) had smaller ovarian volume per ovary than controls (median, 4.8 vs. 6.8 cm(3); P < 0.001) and a lower number of antral follicles per ovary (median, 7.5 vs. 11; P < 0.001). Further, they had lower inhibin B levels than controls (median, 94 vs. 111 pg/ml; P = 0.03) and higher estradiol levels (median, 0.12 vs. 0.08 pM; P = 0.04). Multiple linear regression analysis was performed to predict the total antral follicle number per ovary, and it showed a reduced number with ovarian irradiation (beta = -0.40, P < 0.001), alkylating chemotherapy (beta = -0.25, P = 0.01), older age at diagnosis (beta = -0.25, P = 0.01), and longer time period off treatment (beta = -0.19, P = 0.044). One in every six female survivors may develop premature ovarian failure. In survivors with spontaneous menstrual cycles, the results indicate a diminished ovarian reserve. Consequently, cessation of fertility may occur much earlier than anticipated. Adult survivors with spontaneous cycles should be informed hereof to plan childbearing.