The effect of tamoxifen on the function and lifespan of the corpus luteum and on subsequent ovarian function

1989 ◽  
Vol 121 (3) ◽  
pp. 417-425 ◽  
Author(s):  
M. L. Swahn ◽  
M. Bygdeman ◽  
S. A. Matlin ◽  
Z. Y. Wu
Keyword(s):  
Corpus Luteum ◽  
Ovarian Function ◽  
Treatment Cycle ◽  
Bleeding Pattern ◽  
Secretory Phase ◽  
Luteal Function ◽  
Menstrual Cycles ◽  
17 Hydroxyprogesterone ◽  
Estrone Sulphate

Abstract. The aim of the present study was to investigate the effects of tamoxifen on pituitary and luteal function and on the bleeding pattern when administered continuously in the secretory phase. The study included 16 women with regular menstrual cycles followed during one control, one treatment and one follow-up cycle. Each volunteer received 20 mg tamoxifen twice daily from cycle day 18 to menstruation in the treatment cycle. The luteal phase was slightly, but significantly prolonged during treatment, and FSH, progesterone, 17-hydroxyprogesterone, 20α-dihydro progesterone, estrone, estrone sulphate and estradiol significantly elevated in comparison with corresponding data during the control cycle. The results indicate that estrogen may be of some importance for the regulation of the life span of the corpus luteum in the human. The significantly elevated levels of pregnanediol glucuronide and estrone glucuronide during the follow-up cycle are most likely a result of either a direct effect of remaining circulating tamoxifen levels on the ovary, or mediated through the increased release of FSH. If estrogens are of importance for the process of implantation, which has recently been suggested in subhuman primates, also in the human remains unclear. Studies on the effect of anti-estrogens on the endometrium during the secretory phase of the cycle are ongoing.

THE NEUTRAL 17-KETOSTEROID EXCRETION DURING THE MENSTRUAL CYCLE

1960 ◽  
Vol XXXIII (IV) ◽  
pp. 494-500 ◽  
Author(s):  
L. G. Huis in 't Veld
Keyword(s):  
Menstrual Cycle ◽  
Urinary Excretion ◽  
Corpus Luteum ◽  
Addison’S Disease ◽  
Bilateral Adrenalectomy ◽  
Addison's Disease ◽  
Menstrual Cycles ◽  
17 Hydroxyprogesterone

ABSTRACT The excretion of Zimmermann chromogens was determined during 3 menstrual cycles in a woman with regular menstruation, suffering from Addison's disease following bilateral adrenalectomy. The 3 cycles investigated were normal (ovulatory) according to the conventional criteria. The medication given (DOCA, deoxycorticosterone-trimethyl-acetate (DOCTA), cortisone) gave rise to the excretion of small quantities of pregnanediol, pregnanolones and 11-oxygenated 17-ketosteroids in the urine. The progesterone produced in the corpus luteum gave rise to urinary excretion of pregnanediol and probably pregnanolones. The results obtained indicate that the ovarian secretion of precursors of 17-ketosteroids (17-hydroxyprogesterone and androst-4-en-3,17-dione) must be exceedingly small. No findings were obtained which indicate the existence of cyclic fluctuations in the ovarian secretion of precursors of neutral 17-ketosteroids.

Regulation of functional and regressing stages of corpus luteum development in mice. Role of reactive oxygen species

2008 ◽  
Vol 20 (7) ◽  
pp. 760 ◽  
Author(s):  
Valeria A. Sander ◽  
Lidia Piehl ◽  
Graciela B. Facorro ◽  
Emilio Rubín de Celis ◽  
Alicia B. Motta
Keyword(s):  
T Cells ◽  
Corpus Luteum ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Radical Scavenger ◽  
Luteal Function ◽  
The Status ◽  
Oxidant Status ◽  
Total Superoxide Dismutase

The endocrine and immune systems modulate ovarian function. The aim of the present work was to compare the status of various modulating factors in two well-defined stages of corpus luteum (CL) development (the functional stage and the regressing stage) by means of a gonadotropin-synchronised mouse model. At the regressing stage of CL development, we found that ovarian tissue showed increased prostaglandin (PG) F2α and diminished PGE levels concomitantly with enhanced protein abundance of ovarian cyclooxygenase 2, the inducible isoform of the limiting enzyme of PG synthesis. We also found both enhanced lipid peroxidation and enhanced total superoxide dismutase activity, as well as inhibited catalase activity and inhibited total hydroxyl radical scavenger capacity, when compared with ovaries at the functional stage. In addition, at the regressing stage we observed an increased percentage of CD8+ (cytotoxic/suppressor) T-cells and a decreased percentage of CD4+ (helper) T-cells from ovarian-draining lymph nodes. Also, the serum interleukin (IL)-2, IL-4 and IL-10 were diminished as compared with the functional stage. We conclude that a pro-oxidant status together with a pro-inflammatory response is responsible for the loss of luteal function.

scholarly journals OR31-05 Emergence of Ovarian Hyperandrogenism and Luteal Insufficiency Following ESR1 Knockdown in the Mediobasal Hypothalamus of Adult Female Rhesus Monkeys

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jon E Levine ◽  
Emily P Greinwald ◽  
Jesi A Felton ◽  
Matthew T Flowers ◽  
Molly M Willging ◽  
...  
Keyword(s):  
Adult Female ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Mediobasal Hypothalamus ◽  
Serum Samples ◽  
Gadolinium Contrast ◽  
Menstrual Cycles ◽  
Female Rhesus ◽  
Luteal Insufficiency ◽  
Ovarian Hyperandrogenism

Abstract Diminished estradiol (E2) negative feedback action by neuronal ESR1 in the arcuate nucleus (ARC) of the mediobasal hypothalamus (MBH) is hypothesized to cause gonadotropin-releasing hormone (GnRH) hypersecretion, and thus LH excess, contributing to ovarian hyperandrogenism in polycystic ovary syndrome (PCOS). In primates, including humans, however, the mediating estrogen receptor is unknown. Thus, to test the hypothesis that diminished E2 action on ARC ESR1 contributes to female primate ovarian hyperandrogenism, eleven, ovary intact, adult female rhesus macaques, pair housed with female peers, received five 12µl MRI-guided MBH infusions into the rostral-to-caudal extent of both right and left ARC. Each infusion comprised gadolinium contrast agent and ~3-4 x 1010 adeno-associated virus 8 (AAV8) particles containing either a shRNA specific for ESR1 (n=6, ERaKD) or scrambled shRNA (n=5, control). Mid-surgery MRI scans identified targeting accuracy. 2-2.5 years following AAV8 infusion, EIA-determined P4 values were obtained from twice weekly serum samples; samples obtained during the follicular phase of menstrual cycles or anovulatory periods were submitted to liquid chromatography, tandem mass spectrometry (LCMS) for additional steroid hormones. LCMS-determined values were also obtained 0 hours (h) and 24 h following an IM injection of 200IU hCG. Both ERaKD (28.5 ± 1.3 days, mean ± SEM) and control (34.0 ± 3.3 days) female groups exhibited comparably regular menstrual cycles. ERaKD exhibited higher circulating levels of LH (2.8 ± 0.2 ng/ml, p=0.03), androstenedione (A4, 0.43 ± 0.03 ng/ml, p=0.03) and testosterone (T, 0.23 ± 0.03 ng/ml, p=0.09), and LH/FSH ratio (1.7 ± 0.2, p=0.05) compared to controls (LH, 2.1 ± 0.4; A4, 0.30 ± 0.05; T, 0.18 ± 0.01 ng/ml; LH/FSH 1.3 ± 0.2). Following an ovarian androgen-stimulating hCG injection, ERaKD 24-h peak levels for T (0.28 ± 0.01 ng/ml) were higher (p=0.03) compared to controls (0.21 ± 0.01 ng/ml). In addition, luteal insufficiency emerged in ERaKD females, with mean (2.4 ± 0.3 ng/ml), peak (3.6 ± 0.4 ng/ml) and area-under-the-curve (AUC, 23.2 ± 4.2 ng/ml/days) P4 values diminished compared to controls (mean, 3.6 ± 0.1, p=0.01; peak 5.7 ± 0.1 ng/ml, p=0.01; AUC, 43.7 ± 6.7 ng/ml/days, p=0.03). Taken together, these results suggest that knockdown of ARC ESR1 disrupts Gn stimulation of ovarian function, contributing to female monkey ovarian hyperandrogenism and menstrual cycle impairment emulating PCOS in women.

scholarly journals Post-hospitalization Daycare Treatment for Adolescents With Eating Disorders

2021 ◽  
Vol 12 ◽  
Author(s):  
Liron Litmanovich-Cohen ◽  
Amit Yaroslavsky ◽  
Liron Roni Halevy-Yosef ◽  
Tal Shilton ◽  
Adi Enoch-Levy ◽  
...  
Keyword(s):  
Eating Disorders ◽  
Social Functioning ◽  
Inpatient Treatment ◽  
Semistructured Interview ◽  
Normal Range ◽  
Post Discharge ◽  
Menstrual Cycles ◽  
Self Rating ◽  
Remission Criteria

Background: There are several possible facilities for the treatment of eating disorders (EDs). Specifically, there is the issue of the use of specialized daycare and ambulatory services over inpatient settings and the place of daycare programs following inpatient treatment.Aim: We sought to examine the contribution of post-hospitalization daycare program to the treatment of adolescents hospitalized with an ED.Methods: We assessed 61 female adolescents hospitalized with an ED. All but three were diagnosed with clinical or subthreshold anorexia nervosa (AN). Three were diagnosed with bulimia nervosa. Thirty-seven patients continued with a post-hospitalization daycare program for at least 5 months, whereas 24 did not enter or were enrolled in the program for <5 months. Patients completed on admission to, and discharge from, inpatient treatment self-rating questionnaires assessing ED-related symptoms, body-related attitudes and behaviors, and depression and anxiety. Social functioning was assessed 1 year from discharge using open-ended questions. One-year ED outcome was evaluated according to the patients' body mass index (BMI) and according to composite remission criteria, assessed with a standardized semistructured interview. To be remitted from an ED, patients were required to maintain a stable weight, to have regular menstrual cycles, and not to engage in binging, purging, and restricting behaviors for at least eight consecutive weeks before their assessment.Results: BMI was within normal range at follow-up, whether completing or not completing daycare treatment, and around 75% of the patients had menstrual cycles. By contrast, when using comprehensive composite remission criteria, less than a quarter of former inpatients not entering/not completing daycare program achieved remission vs. almost a half of the completers. In addition, a greater percentage of completers continued with psychotherapy following discharge. Fifty percent of both groups showed good post-discharge social functioning. No between-group differences were found in the BMI and the scores of the self-rating questionnaires at admission to, and discharge from, inpatient treatment.Conclusion: Adolescent females with EDs can maintain a normal-range BMI from discharge to 1-year follow-up, even if not completing daycare treatment. By contrast, completion of a post-hospitalization daycare program may improve the 1-year follow-up ED-related outcome of former ED inpatients.

Blood perfusion and diameter of bovine corpus luteum as predictors of luteal function in early pregnancy

2021 ◽  
Author(s):  
Gabriella dos Santos Velho ◽  
Monique Tomazele Rovani ◽  
Rogério Ferreira ◽  
Bernardo Garziera Gasperin ◽  
André Gustavo Cabrera Dalto
Keyword(s):  
Corpus Luteum ◽  
Early Pregnancy ◽  
Blood Perfusion ◽  
Luteal Function ◽  
Bovine Corpus Luteum

Final analysis of the PROMISE-GIM6 phase III trial assessing GnRH agonist use during chemotherapy as a strategy to preserve ovarian function in premenopausal patients with early breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 516-516
Author(s):  
Matteo Lambertini ◽  
Luca Boni ◽  
Andrea Michelotti ◽  
Emanuela Magnolfi ◽  
Alessio Aligi Cogoni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Ovarian Function ◽  
Final Analysis ◽  
Post Treatment ◽  
Phase Iii ◽  
Hormone Receptor Positive ◽  
Premenopausal Patients

516 Background: Current guidelines recommend GnRH agonist (GnRHa) use during chemotherapy (CT) as a strategy to reduce the risk of premature ovarian insufficiency (POI) in premenopausal patients with early breast cancer (EBC). However, no long-term safety data are available raising some concerns on concurrent use of GnRHa during CT in patients with hormone receptor-positive disease. In addition, there is no evidence on the protective role of this strategy in patients with germline BRCA mutations ( mBRCA). Here, we report the final analysis of the PROMISE-GIM6 phase III randomized study, the largest trial addressing the role of GnRHa use during CT in premenopausal EBC patients (Del Mastro et al, JAMA 2011 & Lambertini et al, JAMA 2015). Methods: From October 2003 to January 2008, 281 premenopausal patients aged 18 to 45 years with stage I-III EBC candidates for (neo)adjuvant CT were randomized to receive CT alone or combined with the GnRHa triptorelin. Primary endpoint was incidence of CT-induced POI (defined as amenorrhea and post-menopausal FSH/estradiol levels 1 year following CT). This final analysis reports on post-treatment pregnancies, disease-free survival (DFS) and overall survival (OS). An exploratory descriptive analysis in mBRCA patients is also reported. (ClinicalTrial.gov: NCT00311636) Results: Of the 281 randomized patients (CT+GnRHa arm = 148; CT alone arm = 133), 80% had hormone receptor-positive disease. At the time of this final analysis, 38 (13.5%) patients were lost to follow-up. Median follow-up was 12.4 years (IQR: 11.3-13.2 years). In the CT+GnRHa and CT alone arms, respectively, 9 (10-year cumulative incidence of pregnancy 6.5%, 95% CI 3.5%-12.3%) and 4 (10-year cumulative incidence of pregnancy 3.2%, 95% CI 1.2%-8.3%) patients had a post-treatment pregnancy (HR 2.14, 95% CI 0.66-6.92). No differences in 10-year DFS (72.4% in CT+GnRHa arm vs. 71.2% in CT alone arm: HR 1.16, 95% CI 0.76-1.77) nor in 10-year OS (82.0% in CT+GnRHa arm vs. 85.9% in CT alone arm: HR 1.17, 95% CI 0.67-2.03) were observed. There was no interaction between treatment effect and hormone receptor status. In patients with hormone receptor-positive disease, HR was 1.02 (95% CI 0.63-1.63) for DFS and 1.12 (95% CI 0.59-2.11) for OS. Out of 43 patients tested for BRCA, overall incidence of POI, irrespective of treatment arm, was 20% in mBRCA patients (n = 10) and 12% in patients without mBRCA (n = 33). In mBRCA patients, incidence of POI was 0% and 33% in the CT+GnRHa and CT alone arms, respectively. One post-treatment pregnancy was described in a patient with mBRCA1 in the CT alone arm. Conclusions: The final analysis of the PROMISE-GIM6 trial at a median follow-up of 12.4 years provides reassuring evidence on the safety of GnRHa use during CT as a strategy to preserve ovarian function in premenopausal patients with hormone receptor-positive EBC. Clinical trial information: NCT00311636.

scholarly journals Gonadotropin Glycoforms Circulating in Women Using Progestins of the Levonorgestrel Family for Contraception

2020 ◽  
Vol 4 (11) ◽  
Author(s):  
Karin Eriksson ◽  
Leif Wide
Keyword(s):  
Luteinizing Hormone ◽  
Outcome Measures ◽  
Half Life ◽  
Treatment Cycle ◽  
Follicle Stimulating Hormone ◽  
Serum Levels ◽  
Follicular Phase ◽  
Serum Samples ◽  
Menstrual Cycles ◽  
Contraceptive Effect

Abstract Context The progestins of the levonorgestrel family are 13-ethylgonane progestins, commonly used for contraception in women. One contraceptive effect of these progestins is inhibition of ovulation, which may be a result of changes in gonadotropin glycosylation patterns. Gonadotropin glycoforms differ in number of glycans and bioactivity: more bioactive low-N-glycosylated glycoforms, diglycosylated luteinizing hormone (LHdi) and triglycosylated follicle-stimulating hormone (FSHtri), and less bioactive fully N-glycosylated glycoforms, LHtri and FSHtetra. Objective Characterize the glycosylation patterns on the circulating gonadotropin glycoforms in women using 13-ethylgonane progestins for contraception. Design, Subjects, Main Outcome Measures Serum samples, collected from 92 healthy women using 13-ethylgonane progestins for contraception, were included. Forty women used progestin-only continuously and 52 used progestins combined with ethinylestradiol (EE) for 3 weeks followed by a hormone-free week. Concentration, sulfonation, and sialylation of each glycoform were determined and compared with follicular phase values of normal menstrual cycles. Results The progestin-only group had significantly increased serum levels, decreased sulfonation, and increased sialylation of LHdi. The LHdi/FSHtri ratio was increased. The progestin+EE group had significantly decreased gonadotropin glycoform concentrations and decreased sialylation of FSHtri. The progestin+EE effect on sialylation of FSHtri occurred later during the treatment cycle in contrast to the effect on FSHtri concentration. Conclusions The 2 different progestin treatments induced different effects on the glycan synthesis and concentrations of more bioactive low-glycosylated gonadotropins. Progestin-only treatment increased sialylation and decreased sulfonation of LHdi molecules, contributing to sustained higher levels of bioactive LHdi molecules. Progestin+EE treatment decreased sialylation of FSHtri, contributing to a shorter half-life and decreased levels of bioactive FSHtri.

scholarly journals Menstrual cycle regularity and length across the reproductive lifespan and risk of premature mortality: prospective cohort study

BMJ ◽  
2020 ◽  
pp. m3464 ◽  
Author(s):  
Yi-Xin Wang ◽  
Mariel Arvizu ◽  
Janet W Rich-Edwards ◽  
Jennifer J Stuart ◽  
JoAnn E Manson ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cohort Study ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Cycle Length ◽  
Premature Mortality ◽  
Health Study ◽  
Menstrual Cycles ◽  
Hazard Ratios

AbstractObjectiveTo evaluate whether irregular or long menstrual cycles throughout the life course are associated with all cause and cause specific premature mortality (age <70 years).DesignProspective cohort study.SettingNurses’ Health Study II (1993-2017).Participants79 505 premenopausal women without a history of cardiovascular disease, cancer, or diabetes and who reported the usual length and regularity of their menstrual cycles at ages 14-17 years, 18-22 years, and 29-46 years.Main outcome measuresHazard ratios and 95% confidence intervals for all cause and cause specific premature mortality (death before age 70 years) were estimated from multivariable Cox proportional hazards models.ResultsDuring 24 years of follow-up, 1975 premature deaths were documented, including 894 from cancer and 172 from cardiovascular disease. Women who reported always having irregular menstrual cycles experienced higher mortality rates during follow-up than women who reported very regular cycles in the same age ranges. The crude mortality rate per 1000 person years of follow-up for women reporting very regular cycles and women reporting always irregular cycles were 1.05 and 1.23 for cycle characteristics at ages 14-17 years, 1.00 and 1.37 for cycle characteristics at ages 18-22 years, and 1.00 and 1.68 for cycle characteristics at ages 29-46 years. The corresponding multivariable adjusted hazard ratios for premature death during follow-up were 1.18 (95% confidence interval 1.02 to 1.37), 1.37 (1.09 to 1.73), and 1.39 (1.14 to 1.70), respectively. Similarly, women who reported that their usual cycle length was 40 days or more at ages 18-22 years and 29-46 years were more likely to die prematurely than women who reported a usual cycle length of 26-31 days in the same age ranges (1.34, 1.06 to 1.69; and 1.40, 1.17 to 1.68, respectively). These relations were strongest for deaths related to cardiovascular disease. The higher mortality associated with long and irregular menstrual cycles was slightly stronger among current smokers.ConclusionsIrregular and long menstrual cycles in adolescence and adulthood are associated with a greater risk of premature mortality (age <70 years). This relation is slightly stronger among women who smoke.

Role of melatonin on embryo viability in sheep

2019 ◽  
Vol 31 (1) ◽  
pp. 82 ◽  
Author(s):  
José-Alfonso Abecia ◽  
Fernando Forcada ◽  
María-Isabel Vázquez ◽  
Teresa Muiño-Blanco ◽  
José A. Cebrián-Pérez ◽  
...  
Keyword(s):  
Pineal Gland ◽  
Corpus Luteum ◽  
Embryo Quality ◽  
Protective Action ◽  
Embryo Viability ◽  
Embryo Survival ◽  
Luteal Function ◽  
Seasonal Rhythms ◽  
Natural Hormone

Melatonin is a natural hormone synthesised in the pineal gland, the activity of which is regulated by day–night perception and dictates seasonal rhythms in reproduction in ovine species. Exogenous melatonin, administered via subcutaneous implants, is used to prolong the breeding season of ewes and can increase the proportion of pregnant ewes (fertility rate) and litter size. The increased proportion of ewes that become pregnant and the number of lambs born per lambing among melatonin-treated sheep may be caused by increased embryo survival, through enhanced luteal function, reduced antiluteolytic mechanisms, or improved embryo quality. This review focuses on the effects of melatonin on embryo viability and summarises the processes by which this hormone affects the ovary, follicle, oocyte, corpus luteum and embryo. Moreover, the effects of melatonin on the mechanisms of invivo maternal recognition of pregnancy in sheep and the protective action that it appears to have on the invitro procedures that are used to obtain healthy embryos are reviewed.

scholarly journals Biopsying, fragmentation and autotransplantation of fresh ovarian cortical tissue in infertile women with diminished ovarian reserve

2019 ◽  
Vol 34 (10) ◽  
pp. 1924-1936 ◽  
Author(s):  
Stine Aagaard Lunding ◽  
Susanne Elisabeth Pors ◽  
Stine Gry Kristensen ◽  
Selma Kloeve Landersoe ◽  
Janni Vikkelsø Jeppesen ◽  
...  
Keyword(s):  
Ovarian Reserve ◽  
Ovarian Stimulation ◽  
Clinical Pregnancy ◽  
Cortical Tissue ◽  
Donor Sperm ◽  
Menstrual Cycles ◽  
Infertile Women ◽  
Icsi Cycle ◽  
Per Se

Abstract STUDY QUESTION Can ovarian biopsying per se and/or autotransplantation of fragmented ovarian cortical tissue activate dormant follicles and increase the number of recruitable follicles for IVF/ICSI in women with diminished ovarian reserve (DOR)? SUMMARY ANSWER Ovarian biopsying followed by immediate autotransplantation of fragmented cortical tissue failed to increase the number of recruitable follicles for IVF/ICSI 10 weeks after the procedure either at the graft site or in the biopsied ovary, but 12 of the 20 women subsequently had a clinical pregnancy during the 1-year follow-up. WHAT IS KNOWN ALREADY Infertile women with DOR constitute a group of patients with poor reproductive outcome mainly due to the low number of mature oocytes available for IVF/ICSI. Recent studies have shown that in vitro activation of residual dormant follicles by both chemical treatment and tissue fragmentation has resulted in return of menstrual cycles and pregnancies in a fraction of amenorrhoeic women with premature ovarian insufficiency. STUDY DESIGN, SIZE, DURATION This is a prospective clinical cohort study including 20 women with DOR treated at the fertility clinic, Rigshospitalet, Denmark, during April 2016–December 2017. Non-pregnant patients were on average followed for 280 days (range 118–408), while women who conceived were followed until delivery. Study follow-up of non-pregnant patients ended in September 2018. PARTICIPANTS, MATERIALS, SETTING, METHODS The study included infertile women aged 30–39 years with preserved menstrual cycles, indication for IVF/ICSI and repeated serum measurements of anti-Müllerian hormone (AMH) ≤ 5 pmol/L. Patients were randomized to have four biopsies taken from either the left or the right ovary by laparoscopy followed by fragmentation of the cortical tissue to an approximate size of 1 mm3 and autotransplanted to a peritoneal pocket. The other ovary served as a control. Patients were followed weekly for 10 weeks with recording of hormone profile, antral follicle count (AFC), ovarian volume and assessment for ectopic follicle growth. After 10 weeks, an IVF/ICSI-cycle with maximal ovarian stimulation was initiated. MAIN RESULTS AND THE ROLE OF CHANCE No difference in the number of mature follicles after ovarian stimulation 10 weeks after the procedure in the biopsied versus the control ovaries was observed (1.0 vs. 0.7 follicles, P = 0.35). In only three patients, growth of four follicles was detected at the graft site 24–268 days after the procedure. From one of these follicles, a metaphase II (MII) oocyte was retrieved and fertilized, but embryonic development failed. Overall AMH levels did not change significantly after the procedure (P = 0.2). The AFC increased by 0.14 (95% CI: 0.06;0.21) per week (P < 0.005), and the biopsied ovary had on average 0.6 (95% CI: 0.3;−0.88) follicles fewer than the control ovary (P = 0.01). Serum levels of androstenedione and testosterone increased significantly by 0.63 nmol/L (95% CI: 0.21;1.04) and 0.11 nmol/L (95% CI: 0.01;0.21) 1 week after the procedure, respectively, and testosterone increased consecutively over the 10 weeks by 0.0095 nmol/L (95% CI: 0.0002;0.0188) per week (P = 0.045). In 7 of the 20 patients, there was a serum AMH elevation 5 to 8 weeks after the procedure. In this group, mean AMH increased from 2.08 pmol/L (range 1.74–2.34) to 3.94 pmol/L (range 3.66–4.29) from Weeks 1–4 to Weeks 5–8. A clinical pregnancy was obtained in 12 of the 20 (60%) patients with and without medically assisted reproduction (MAR) treatments. We report a cumulated live birth rate per started IVF/ICSI cycle of 18.4%. LIMITATIONS, REASON FOR CAUTION Limitations of the study were the number of patients included and the lack of a non-operated control group. Moreover, 9 of the 20 women had no male partner at inclusion and were treated with donor sperm, but each of these women had an average of 6.8 (range 4–9) unsuccessful MAR treatments with donor sperm prior to inclusion. WIDER IMPLICATIONS OF THE FINDINGS Although 12 out of 20 patients became pregnant during the follow-up period, the current study does not indicate that biopsying, fragmenting and autotransplanting of ovarian cortical tissue increase the number of recruitable follicles for IVF/ICSI after 10 weeks. However, a proportion of the patients may have a follicular response in Weeks 5–8 after the procedure. It could therefore be relevant to perform a future study on the possible effects of biopsying per se that includes stimulation for IVF/ICSI earlier than week 10. STUDY FUNDING/COMPETING INTEREST(S) This study is part of the ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS. The funders had no role in the study design, data collection and interpretation, or decision to submit the work for publication. None of the authors have a conflict of interest. TRIAL REGISTRATION NUMBER NCT02792569.

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