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Intraovarian injection of autologous human mesenchymal stem cells increases estrogen production and reduces menopausal symptoms in women with premature ovarian failure: two case reports and a review of the literature.

ABSTRACT: BACKGROUND:Premature ovarian failure is a relatively common condition that affects 1-3% of adult women. Premature ovarian failure occurs when there is loss of ovarian function in women younger than 40?years of age. The causes are mostly iatrogenic or idiopathic. Amenorrhea and infertility are the most important clinical manifestations. So far, no therapeutic intervention has been proved effective in restoring fertility in patients with premature ovarian failure. Attempts to stimulate ovarian function through hormone manipulation typically prove unsuccessful, and patients usually resort to egg donation to achieve pregnancy. In our preclinical work, intraovarian administration of human bone marrow-derived mesenchymal stem cells was able to restore ovarian hormone production, reactivate folliculogenesis, and reverse infertility in a chemotherapy-induced ovarian failure mouse model. CASE PRESENTATION:We present two cases of Caucasian women with premature ovarian failure who resumed ovarian estrogen production and menses 7?months following autologous bone marrow-derived mesenchymal stem cell injections into the ovary. This pilot clinical study is registered with ClinicalTrials.gov (identifier NCT02696889 ). In this report, we present data from our first two cases that have completed study procedures so far. The bone marrow-derived mesenchymal stem cells were harvested from the bone marrow of the iliac crest of the patients with premature ovarian failure and nucleated cells concentrated and enriched in bone marrow-derived mesenchymal stem cells intraoperatively, and then injected into the patient's right ovary via laparoscopy. Autologous bone marrow stem cell engraftment into the ovary resulted in several improvements in the treated patients with premature ovarian failure. In measurements by transvaginal ultrasound, there were increases of approximately 50% in volume of the treated ovaries in comparison with the contralateral control ovaries that persisted to the end of the study (1 year). Serum levels of estrogen increased by approximately 150% compared with the preoperative levels. Each of the two patients had an episode of menses, and also both of them reported marked improvement of their menopausal symptoms that also persisted to the end of the study (1 year). The bone marrow-derived mesenchymal stem cell implantation procedure was very well tolerated with no reported adverse events. CONCLUSIONS:Our study reveals promising improvement of premature ovarian failure-related clinical manifestations in two patients after intraovarian autologous bone marrow-derived mesenchymal stem cells engraftment. These early observations call for additional assessment and further development of intraovarian bone marrow-derived mesenchymal stem cell injection for possible treatment of patients with premature ovarian failure.

SUBMITTER: Igboeli P

PROVIDER: S-EPMC7368722 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Intraovarian injection of autologous human mesenchymal stem cells increases estrogen production and reduces menopausal symptoms in women with premature ovarian failure: two case reports and a review of the literature.

Igboeli Prosper P El Andaloussi Abdeljabar A Sheikh Ujalla U Takala Hajra H ElSharoud Amro A McHugh Ashley A Gavrilova-Jordan Larisa L Levy Steven S Al-Hendy Ayman A

Journal of medical case reports 20200718 1

<h4>Background</h4>Premature ovarian failure is a relatively common condition that affects 1-3% of adult women. Premature ovarian failure occurs when there is loss of ovarian function in women younger than 40 years of age. The causes are mostly iatrogenic or idiopathic. Amenorrhea and infertility are the most important clinical manifestations. So far, no therapeutic intervention has been proved effective in restoring fertility in patients with premature ovarian failure. Attempts to stimulate ova ...[more]

PMID: 32680541

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Project description:BackgroundAssisted reproduction faces a significant obstacle in the form of poor ovarian response (POR) to controlled ovarian stimulation. To address this challenge, mesenchymal stem cell therapy has been proposed as a potential treatment for female infertility and/or restoration of ovarian function in POR women. Our previous research has demonstrated that menstrual blood-derived-mesenchymal stromal cells (MenSCs) injected into the ovaries of women with POR can increase pregnancy rates. The objective of this study was to examine whether MenSC therapy could enhance ovarian reserve parameters and pregnancy outcomes in a larger population of individuals with POR.MethodThis study consisted of 180 infertile individuals with POR who declined oocyte donation. Participants were divided into two groups: those who received bilateral MenSCs intraovarian injection and those who received no intervention. Our primary aim was to compare the rates of spontaneous pregnancy between the two groups, followed by an investigation of any alterations in the ovarian reserve parameters, such as serum FSH, AMH, and AFC levels, as well as the ICSI/IVF outcomes, in both groups of participants.ResultsThe MenSC therapy exhibited a favourable tolerability profile and did not raise any safety concerns. Following the 2-month follow-up period, women who received MenSC treatment demonstrated a significantly higher rate of spontaneous pregnancy (P < 0.005) and an improvement in anti-Müllerian hormone (AMH) levels (P = 0.0007) and antral follicle count (AFC) (P < 0.001), whereas the control group demonstrated a considerable decline in these parameters (Both P < 0.001). The MenSC therapy led to a greater number of mature oocytes and embryos among women who underwent ICSI/IVF. Our age subgroup analysis demonstrated a significant difference in the number of spontaneous pregnancies and ICSI/IVF outcomes between the treatment and control groups only among individuals below 40 years of age.ConclusionThe results of our study indicate that MenSCs treatment may be a viable option for treating women experiencing POR. However, in order to be widely implemented in clinical practice, the clinical effectiveness of MenSCs therapy will need to be established through rigorous prospective randomized clinical trials.Trial registrationClinicalTrials.gov Identifier: NCT05703308. Registered 01/26/2023, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05703308 . IRCT, IRCT20180619040147N4. Registered 08/01/2020.

Project description:OBJECTIVE:To describe the association between postmenopausal estrogen-only therapy use and risk of ovarian carcinoma, specifically with regard to disease histotype and duration and timing of use. METHODS:We conducted a pooled analysis of 906 women with ovarian carcinoma and 1,220 women in a control group; all 2,126 women included reported having had a hysterectomy. Ten population-based case-control studies participating in the Ovarian Cancer Association Consortium, an international consortium whose goal is to combine data from many studies with similar methods so reliable assessments of risk factors can be determined, were included. Self-reported questionnaire data from each study were harmonized and conditional logistic regression was used to examine estrogen-only therapy's histotype-specific and duration and recency of use associations. RESULTS:Forty-three and a half percent of the women in the control group reported previous use of estrogen-only therapy. Compared with them, current or recent estrogen-only therapy use was associated with an increased risk for the serous (51.4%, odds ratio [OR] 1.63, 95% confidence interval [CI] 1.27-2.09) and endometrioid (48.6%, OR 2.00, 95% CI 1.17-3.41) histotypes. In addition, statistically significant trends in risk according to duration of use were seen among current or recent postmenopausal estrogen-only therapy users for both ovarian carcinoma histotypes (Ptrend<.001 for serous and endometrioid). Compared with women in the control group, current or recent users for 10 years or more had increased risks of serous ovarian carcinoma (36.8%, OR 1.73, 95% CI 1.26-2.38) and endometrioid ovarian carcinoma (34.9%, OR 4.03, 95% CI 1.91-8.49). CONCLUSION:We found evidence of an increased risk of serous and endometrioid ovarian carcinoma associated with postmenopausal estrogen-only therapy use, particularly of long duration. These findings emphasize that risk may be associated with extended estrogen-only therapy use.

Project description:BackgroundCoronary microvascular dysfunction results in angina and adverse outcomes in patients with evidence of ischemia and nonobstructive coronary artery disease; however, no specific therapy exists. CD34+ cell therapy increases microvasculature in preclinical models and improves symptoms, exercise tolerance, and mortality in refractory angina patients with obstructive coronary artery disease. The objective of this research was to evaluate the safety, tolerability, and efficacy of intracoronary CD34+ cell therapy in patients with coronary microvascular dysfunction.MethodsWe conducted a 2-center, 20-participant trial of autologous CD34+ cell therapy (protocol CLBS16-P01; NCT03508609) in patients with ischemia and nonobstructive coronary artery disease with persistent angina and coronary flow reserve ≤2.5. Efficacy measures included coronary flow reserve, angina frequency, Canadian Cardiovascular Society angina class, Seattle Angina Questionnaire, SF-36, and modified Bruce exercise treadmill test obtained at baseline and 6 months after treatment. Autologous CD34+ cells (CLBS16) were mobilized by administration of granulocyte-colony stimulating factor 5µg/kg/day for 5 days and collected by leukapheresis. Participants received a single intracoronary left anterior descending infusion of isolated CD34+ cells in medium that enhances cell function.ResultsCoronary flow reserve improved from 2.08±0.32 at baseline to 2.68±0.79 at 6 months after treatment (P<0.005). Angina frequency decreased (P<0.004), Canadian Cardiovascular Society class improved (P<0.001), and quality of life improved as assessed by the Seattle Angina Questionnaire (P≤0.03, all scales) and SF-36 (P≤0.04, all scales). There were no cell-related serious adverse events.ConclusionsIn this pilot clinical trial of microvascular angina, patients with ischemia and nonobstructive coronary artery disease receiving intracoronary infusion of CD34+ cell therapy had higher coronary flow reserve, less severe angina, and better quality of life at 6 months. The current study supports a potential therapeutic role for CD34+ cells in patients with microvascular angina. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03508609.

Dataset Information

Intraovarian injection of autologous human mesenchymal stem cells increases estrogen production and reduces menopausal symptoms in women with premature ovarian failure: two case reports and a review of the literature.

Publications

Intraovarian injection of autologous human mesenchymal stem cells increases estrogen production and reduces menopausal symptoms in women with premature ovarian failure: two case reports and a review of the literature.

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