Ovarian tissue damage after grafting: systematic review of strategies to improve follicle outcomes.

Frozen-thawed human ovarian tissue endures large-scale follicle loss in the early post-grafting period, characterized by hypoxia lasting around 7 days. Tissue revascularization occurs progressively through new vessel invasion from the host and neoangiogenesis from the graft. Such reoxygenation kinetics lead to further potential damage caused by oxidative stress. The aim of the present manuscript is to provide a systematic review of proangiogenic growth factors, hormones and various antioxidants administered in the event of ovarian tissue transplantation to protect the follicle pool from depletion by boosting revascularization or decreasing oxidative stress. Although almost all investigated studies revealed an advantage in terms of revascularization and reduction in oxidative stress, far fewer demonstrated a positive impact on follicle survival. As the cascade of events driven by ischaemia after transplantation is a complex process involving numerous players, it appears that acting on specific molecular mechanisms, such as concentrations of proangiogenic growth factors, is not enough to significantly mitigate tissue damage. Strategies exploiting the activated tissue response to ischaemia for tissue healing and remodelling purposes, such as the use of antiapoptotic drugs and adult stem cells, are also discussed in the present review, since they yielded promising results in terms of follicle pool protection.

Samul-tang ameliorates oocyte damage due to cyclophosphamide-induced chronic ovarian dysfunction in mice.

Samul-tang (SM), a traditional herbal medicine, has been used to treat menstrual irregularities and infertility in women. However, the cellular and molecular mechanisms underlying the effects of SM remain elusive. We investigated the potential protective effect of SM against chronic ovarian dysfunction and used bioinformatics analysis to identify its underlying mechanism in a mouse model of cyclophosphamide (CP)-induced diminished ovarian reserve. Female C57BL/6 mice were intraperitoneally injected with CP three times a week, followed by oral administration of distilled water (CP group) or SM (CP + SM group) for 4 weeks. Four weeks later, the effect of SM was assessed by ovarian tissue histological analysis, steroid hormone measurement, oocyte quality, and mRNA and microRNA microarray analysis in the ovaries. Although SM administration did not prevent CP-induced follicle loss in mice, the quality of oocytes was better in CP + SM mice than in CP mice. Gene expression analysis revealed that the expression of fertilisation- and ovarian follicle development-related genes was altered by CP treatment but normalized after SM administration. Further bioinformatics analysis showed possible interactions between differentially expressed mRNAs and microRNAs. Therefore, we demonstrated the protective effects of SM on ovarian function and oocyte maturation against CP-induced damage via multiple epigenetic mechanisms.

Ultrasound ovarian assessments after endometrioma ablation using plasma energy.

We performed a retrospective three-dimensional ultrasound evaluation of the ovarian features in ten women with no previous ovarian surgery who benefited from ablation by plasma energy for unilateral endometriomas greater than to 30 mm in diameter. Values of ovarian volume and antral follicle count in operated ovaries were decreased by an average 12% and 18%, respectively, suggesting that endometrioma ablation using plasma energy spares the underlying ovarian parenchyma.

Changes in serum anti-Müllerian hormone levels may predict damage to residual normal ovarian tissue after laparoscopic surgery for women with ovarian endometrioma.

We measured serum anti-Müllerian hormone levels before and after surgery in women undergoing unilateral and monolocular cystectomy for benign ovarian diseases. Comparing to control benign cysts, we found a significant decline in serum anti-Müllerian hormone levels with consequent depletion of follicles in tissue specimens after surgery for women with ovarian endometrioma.

[Ovarian stimulation and follicular puncture risks]. / Risques de la stimulation ovarienne et du prélèvement ovocytaire.

The ovarian stimulation and the follicular puncture in ART present risks which must be planned in order to better prevent them. These complications are the ovarian hyperstimulation syndrome, the thromboembolic and carcinologic risks; the anaesthetic, hemorrhagic and infectious risks of the punctures. The presence of an endometrioma can generate an increase in the infectious risk.

Neuroprotection against excitotoxic brain injury in mice after ovarian steroid depletion.

Ovarian steroid hormones influence not only seizure phenomena, but also the neuronal cell death that follows. In the present study, we applied two models of ovarian steroid loss, ovariectomy and chemically-induced ovarian failure, to evaluate kainate-induced seizure activity and the susceptibility of hippocampal neurons to seizure-induced neurodegeneration. Young adult female FVB/NJ mice were ovariectomized with (OVX+E, n=6) or without (OVX, n=8) estrogen replacement. A separate group of females received the ovotoxin, 4-vinylcyclohexene diepoxide (VCD, n=8) to deplete ovarian follicles. Mice underwent kainate-induced status epilepticus and were evaluated for seizure activity (3 h) and delayed hippocampal neuronal injury (7 days). While there were no differences in latency or duration of severe seizures among control, OVX and VCD-treated mice, OVX+E mice exhibited seizures of a significantly longer duration. However, both VCD-induced ovarian failure and OVX led to a dramatic reduction in the extent of excitotoxic cell death, with slightly greater effects observed in VCD-treated mice. Estradiol administration to OVX mice also exerted a significant neuroprotective effect against kainate-induced cell death. These results support and extend earlier findings suggesting that the hormonal milieu may have differential effects on seizure susceptibility that are separate and distinct from those influencing hippocampal neuronal vulnerability. Collectively, these findings highlight the complex interactions among the loss of ovarian steroid hormones, estrogen replacement, seizures, and seizure-induced cell death.

Correlation between serum levels of CA 125 and follicular loss after laparoscopic cystectomy in women with ovarian endometrioma.

STUDY OBJECTIVE: To preoperatively predict follicular loss after laparoscopic cystectomy of ovarian endometriomas. DESIGN: Case-control study. (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Seventy-six women with ovarian endometrioma and 41 patients with nonendometriotic ovarian cysts who underwent laparoscopy. INTERVENTIONS: Sonographic findings and serum levels of CA 125 and CA 19.9 were recorded. MEASUREMENTS AND MAIN RESULTS: Considered parameters were compared with a histologic score, on the basis of the presence and morphologic features of follicles on the normal ovarian tissue adjacent to the cyst wall surgically removed. Serum levels of CA 125 and CA 19.9 were increased in patients with ovarian endometrioma (p <.001 and p <.01, respectively). Capsule wall thickness, presence of fibrosis, and follicles in the tissue surrounding the capsule were significantly increased in the study group (p <.01). CA 125 serum level was directly correlated to the histologic score (r = 0.46, p <.05) and to cyst diameter (r = 0.12, p = .01), whereas no correlation was found between CA 19.9 or cyst diameter and follicular score. CONCLUSIONS: Our data suggest that the ovarian tissue inadvertently removed along with the endometrioma wall by laparoscopic stripping is due to pericystic fibrosis. Serum levels of CA 125 represent a useful parameter to predict follicular loss before surgery.

Puncture of immature ovarian follicles in bovine assisted reproduction.

Transvaginal, ultrasound-guided follicular aspiration (OPU) is the method of choice to retrieve immature oocytes from highly valuable living donor cows for in vitro embryo production. In the introduction, we comment on general techniques of oocyte retrieval. In the second part, we describe the OPU technique from a technical point of view, and we discuss the factors that influence the quality and quantity of the oocytes retrieved. Firstly, there is a group of technical factors such as aspiration procedure, needle type, and the influence of the aspiration vacuum on cumulus oocyte complex morphology. Secondly, there is a huge group of biological influences, e.g. hormonal stimulation prior to follicle puncture, timing of the procedure relative to the estrous cycle, age, breed, and physiological condition of the donor. Subsequently, the use of OPU in combination with in vitro embryo production for the treatment of bovine sterility patients is discussed, as a way to obtain additional offspring from donors with impaired fertility. Reports on donor animal health and reproductive performance following repeated OPU are commented upon. Finally, future research possibilities related to the OPU technique are discussed. Additional gain is expected from the development of better ultrasound equipment, permitting optimal visualization of the smallest follicles. In addition, OPU equipment will be used for related purposes, such as repeated retrieval of ovarian biopsies, and the injection of local ovarian mediators, which will permit to study local paracrine hormonal effects, and their influence on oocyte quality.

Subclinical depletion of primordial follicular reserve in mice treated with cyclophosphamide: clinical importance and proposed accurate investigative tool.

Studies have shown that ovarian failure is a common side-effect of chemotherapy treatment; however, continuation of regular menses post-treatment does not necessarily imply that the ovaries have escaped damage. This animal study measures directly the primordial follicle (PMF) loss following exposure to chemotherapy and evaluates reproductive outcome following significant destruction of the PMF population. Inbred Balb/c mice aged 5-6 weeks were administered different doses of an alkylating agent, cyclophosphamide, and the total number of PMF remaining in both ovaries was counted. Results show that cyclophosphamide causes PMF destruction in proportion to increasing dose (P = 0.0001). Reproductive performance was assessed after exposure to 75 mg/kg cyclophosphamide, a dose which destroys approximately 50% of PMF reserve, by evaluation of ovulation, mating and pregnancy rates. Reproductive potential of treated mice was not affected compared with controls despite the significant loss of PMF. Our results indicate that reproductive performance is not an accurate parameter for assessing ovarian injury. Rather, histological counting of PMF number more directly reflects the damage caused by chemotherapy to the ovary. This method can be used as a sensitive, inexpensive tool to gauge the damage to fertility caused by new chemotherapy agents or protocols.