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.
Lifestyle factors, such as alcohol intake, have placed a substantial burden on
public health. Alcohol consumption is increasing globally due to several factors including
easy accessibility of this addictive substance besides its legal status and social
acceptability. In the US, alcohol is the third leading preventable cause of death (after
tobacco, poor diet and physical inactivity) with an estimated 88,000 people dying from
alcohol-related causes annually, representing 1 in 10 deaths among working adults.
Furthermore, the economic burden of excess drinking costs the US around $249 billion
($191.1 billion related to binge drinking). Although men likely drink more than women do,
women are at much higher risk for alcohol-related problems. Alcohol use is also
considered to be one of the most common non-communicable diseases, which affects
reproductive health. This review article summarizes the current knowledge about
alcohol-related pathogenesis of uterine fibroids (UFs) and highlights the molecular
mechanisms that contribute to the development of UFs in response to alcohol
consumption. Additionally, the effect of alcohol on the levels of various factors that are
involved in UFs pathogenesis, such as steroid hormones, growth factors and cytokines,
are summarized in this review. Animal studies of deleterious alcohol effect and future
directions are discussed as well.
Human chorionic plate-derived mesenchymal stem cells transplantation restores ovarian function in a chemotherapy-induced mouse model of premature ovarian failure.
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