Low level laser therapy (LLLT) modulates ovarian function in mature female mice.

It is known that LLLT has beneficial effects on several pathological conditions including wound healing, pain and inflammation. LLLT modulates biological processes, including cell proliferation, apoptosis and angiogenesis. In the present study, we examined the effect of local application of LLLT on follicular dynamics, ovarian reserve, AMH expression, progesterone levels, apoptosis, angiogenesis, and reproductive outcome in adult mice. LLLT (200 J/cm2) increased the percentage of primary and preantral follicles, whilst decreasing the percentage of corpora lutea compared to control ovaries. LLLT-treated ovaries did not exhibit any changes regarding the number of primordial follicles. We observed a higher percentage of AMH-positive follicles (in early stages of development) in LLLT-treated ovaries compared to control ovaries. LLLT reduced the P4 concentration and the apoptosis in early antral follicles compared to control ones. LLLT caused a reduction in the endothelial cell area and an increase in the periendothelial cell area in the ovary. Additionally, LLLT was able to improve oocyte quality. Our findings suggest that local application of LLLT modulates follicular dynamics by regulating apoptosis and the vascular stability in mouse ovary. In conclusion, these data indicate that LLLT might become a novel and useful tool in the treatment of several pathologies, including female reproductive disorders.

Effects of dehydroepiandrosterone on in vivo ovine follicular development.

STUDY QUESTION: What are the effects of exposure of ovarian tissue to dehydroepiandrosterone (DHEA) supplementation in vivo? SUMMARY ANSWER: DHEA exposure stimulates initiation of primordial follicles and development of gonadotrophin-responsive preantral/early antral follicles possibly mediated through promoting granulosa cell proliferation and enhancing anti-Mullerian hormone (AMH) expression. WHAT IS KNOWN ALREADY?: Ovarian ageing is a cause of subfertility and is associated with poor outcomes of IVF treatment and premature menopause. A few clinical studies have shown that DHEA can improve ovarian response and increase the chances of pregnancy after IVF treatment in women with a diminished ovarian reserve (DOR) suggesting DHEA may help to overcome the effect of ovarian ageing. However, there are no data about how DHEA acts on ovarian folliculogenesis. STUDY DESIGN, SIZE AND DURATION: A cortical autograft experimental model was conducted in six female sheep aged at least 24 months. The period of DHEA treatment in the animals lasted for 10 weeks. PARTICIPANTS/MATERIALS, SETTING, METHODS: All the animals were subjected to unilateral oophorectomy. Half of the ovary was fixed for histological analysis as a time-zero control. The remaining tissue was used to isolate patches of ovarian cortex which were autografted back onto the ovarian pedicle. The grafting procedure eradicated all growing follicles and synchronized early follicular development. After a 10-week treatment period with DHEA implants, the ewes were sacrificed and the graft and remaining ovary were harvested. Histological and immunohistochemistry (IHC) findings, accompanied with serum hormonal profiles were compared to determine the effect on the follicle population. MAIN RESULTS AND THE ROLE OF CHANCE: Higher proportions of the follicle population in the remaining ovary were observed to be in the antral stage after DHEA treatment. The observation coincided with an increase in the rate of primordial follicle initiation and preantral follicle development in cortical grafts and the remaining ovarian tissue, respectively. The IHC results indicated that DHEA increased the expression of both the proliferation marker (KI-67) in granulosa cells and the follicular AMH expression at the preantral and early antral follicle stages. LIMITATIONS, REASONS FOR CAUTION: The experimental design compared follicle populations before and after DHEA treatment within individual animals to allow changes over time to be detected against a background of high inter-animal variation. However, since no controls without DHEA were included, we cannot say what would have happened over time in its absence, and it is possible that other factors may have resulted in the changes in follicle development observed during the experiment. WIDER IMPLICATIONS OF THE FINDING: Our data supports the idea that DHEA might be a useful therapy to delay the effects of ovarian ageing. Therefore, it may have a role as an adjunct during IVF to improve ovarian response in women with DOR and as a treatment for premature ovarian insufficiency. STUDY FUNDING/COMPETING INTEREST(S): The research received finance support from the University of Nottingham. The authors declare no conflict of interest in this study.

Is there a role for DHEA supplementation in women with diminished ovarian reserve?

PURPOSE: Poor ovarian reserve and poor ovarian response presents a challenge to IVF centers. Dehydroepiandrosterone (DHEA) supplementation is increasingly being used by many IVF centers around the world in poor responders despite the lack of convincing data. We therefore examined the rationale for the use of DHEA in poor responders, address the relevant studies, present new data, and address its potential mechanisms of action. METHODS: All published articles on the role of DHEA in infertile women from 1990 to April 2013 were reviewed. RESULTS: Several studies have suggested an improvement in pregnancy rates with the use of DHEA. Potential mechanisms include improved follicular steroidogenesis, increased IGF-1, acting as a pre-hormone for follicular testosterone, reducing aneuploidy, and increasing AMH and antral follicle count. While the role of DHEA is intriguing, evidence-based recommendations are lacking. CONCLUSIONS: While nearly 25 % of IVF programs use DHEA currently, large randomized prospective trials are sorely needed. Until (and if) such trials are conducted, DHEA may be of benefit in suitable, well informed, and consented women with diminished ovarian reserve.

Dehydroepiandrosterone supplementation improves predictive markers for diminished ovarian reserve: serum AMH, inhibin B and antral follicle count.

OBJECTIVE: To evaluate the effect of dehydroepiandrosterone (DHEA) supplementation on ovarian reserve by measuring markers such as antral follicle count, serum anti-Müllerian hormone (AMH) and inhibin B in patients with diminished ovarian reserve. STUDY DESIGN: This prospective study was undertaken at Dr. Zekai Tahir Burak Women's Health Research and Education Hospital, Ankara, Turkey. Forty-one patients with diminished ovarian reserve were included in the study and received supplementation with DHEA 25mg, t.i.d., for at least 6 weeks. Serum AMH, inhibin B, follicle-stimulating hormone (FSH) and oestradiol, and antral follicle count were determined before and after DHEA supplementation. Baseline ovarian reserve parameters such as antral follicle count, FSH, oestradiol, AMH, inhibin B, clinical and laboratory IVF outcomes, and pregnancy rates were studied. RESULTS: There were significant differences in day 3 FSH, oestradiol, antral follicle count, AMH and inhibin B levels before and after DHEA supplementation in all patients (p=0.001, 0.001, 0.002, 0.001 and 0.001, respectively). The study population was divided into two age groups (<35 and ≥35 years) to determine whether there was a difference in the effect of DHEA supplementation between younger and older patients with diminished ovarian reserve. Significant differences were found in all of the parameters in both study groups (p<0.05). CONCLUSIONS: DHEA supplementation is an effective option for patients with diminished ovarian reserve. Prior to assisted reproductive technology, patients with diminished ovarian reserve should be offered DHEA supplementation as an alternative to oocyte donation.

Analysis of androgen receptor and anti-Müllerian hormone pathways in human granulosa cells under luteinizing hormone treatment.

BACKGROUND: The objective of this study was to determine the gene expression profiles of the androgen/androgen receptor (AR) and anti-Müllerian hormone (AMH)/ Sry-related high-mobility group box 9 (SOX9) pathways in granulosa-luteal cells from patients undergoing standard in vitro fertilization (IVF) with or without recombinant luteinizing hormone (rLH) therapy. METHODS: Levels of reproductive hormones in the pre-ovulatory follicular fluid and the expression levels of LHR (luteinizing hormone receptor), AR, SOX9, AMH, AR-associated protein 54(ARA54)and ARA70 were determined in granulosa-luteal cells by real-time reverse-transcription PCR. The effects of androgen and rLH treatments on AR and AMH expression levels were also tested in vitro using HO23 cells. RESULTS: We collected 35 an 70 granulosa cell samples from patients cycled with and without rLH supplementation, respectively. The clinical outcomes were similar in patients who received rLH therapy and those who did not, though the pre-ovulatory follicular fluid levels of androstenedione, testosterone, and estradiol were significantly higher and progesterone was lower in the rLH supplementation group. Moreover, granulosa-luteal cell mRNA levels of LHR, AR, AMH, and SOX9 were significantly higher in the rLH supplementation group relative to the group that did not receive rLH supplementation. In addition, we observed significant correlations between LHR and AR mRNA expression and among AR, AMH, and SOX9 mRNA expression in granulosa-luteal cells from patients undergoing standard IVF treatment. CONCLUSIONS: Increased expression of LHR, AR, AMH, and SOX9 is characteristic of granulosa-luteal cells from IVF/ intracytoplasmic sperm injection (ICSI) patients receiving rLH supplementation.