Predictable increase in female reproductive window: A simple model connecting age of reproduction, menopause, and longevity.

With the ever-increasing lifespan along with societal changes, women can marry and procreate later than in previous centuries. However, pathogenic genetic variants segregating in the population can lead to female subfertility or infertility well before the average age of normal menopause, leading to counter-selection of such deleterious alleles. In reviewing this field, we speculate that a logical consequence would be the later occurrence of menopause and the extension of women's reproductive lifespan. We illustrate this point with a simple model that applies to other variants that contribute to female infertility, including epigenetic variation. We also consider the effect of medical interventions and lifestyle.

Sero-epidemiological assessment of Chlamydia trachomatis infection and sub-fertility in Samoan women.

BACKGROUND: In our recent village-based cross-sectional study, the prevalence of nucleic acid amplification technique (NAAT) diagnosed Chlamydia trachomatis (CT) in sexually active Samoan women was very high (36 %), and test positivity was associated with sub-fertility. We conducted a serological and epidemiological analysis in these participants to identify if serological data can provide further insight into the potential contribution of CT to sub-fertility in this population. METHODS: Serological prediction of CT associated sub-fertility was conducted using a series of commercial tests. The correlation between fertility or sub-fertility, behavioral factors, and serologically predicted CT associated sub-fertility was determined. RESULTS: A positive antibody reaction against the Chlamydia Major Outer Membrane Protein (MOMP) was significantly associated with sub-fertility, with 50 % of infertile women being positive. Serum IgG and IgA antibodies against MOMP correlated with current infection measured by urine NAAT, suggesting longer term infections are common in this population. Chlamydia pneumoniae antibodies were frequently detected in this population (84 %), and unexpectedly, were significantly associated with sub-fertility. CONCLUSIONS: The high prevalence of chlamydial infection and of positive chlamydial sub-fertility results suggests that CT is an important and frequent contributory factor to sub-fertility in this population.

Uterine issues in infertile queens: Nine cases.

This prospective case series investigated potential uterine causes of infertility in queens. Purebred queens with infertility (failure to conceive, embryonic death, or failure to maintain pregnancy and produce viable kittens), but no other reproductive disorders were examined approximately 1-8 weeks before mating (Visit 1), 21 days after mating (Visit 2), and 45 days after mating (Visit 3) if pregnant at Visit 2. Investigations included vaginal cytology and bacteriology, urine bacteriology, and ultrasonography. At Visit 2 or 3, uterine biopsy or ovariohysterectomy was performed for histology. Of nine eligible queens, seven were non-pregnant by ultrasound at Visit 2 and two had lost pregnancies by Visit 3. Ovulation was confirmed by serum progesterone concentration in all queens. Ultrasonic appearance of the ovaries and uterus was compatible with a healthy status except for one queen with signs of cystic endometrial hyperplasia (CEH) and pyometra, a follicular cyst in another, and fetal resorptions in two queens. Six cats had histologic lesions of endometrial hyperplasia, including CEH (n=1). Only one cat had no histologic uterine lesions. Bacteria were cultured from vaginal samples in seven queens at Visit 1, (two were non-evaluable), and in five of seven queens sampled at Visit 2. Uterine cultures were negative except for the cat with pyometra. All urine cultures were negative. In summary, the most frequent pathology observed in these infertile queens was histologic endometrial hyperplasia, which can potentially inhibit embryo implantation and healthy placental development. This suggests that uterine disease might contribute substantially to infertility in purebred queens.

Noninvasive autologous mitochondria transport improves the quality and developmental potential of oocytes from aged mice.

OBJECTIVE: To establish an optimized autologous mitochondria transport technique for oocyte-aging rescue, which minimizes both the patient's pains and the damage to oocytes. DESIGN: Experimental laboratory study. SETTING: Laboratory. ANIMAL(S): Institute of Cancer Research mice. INTERVENTION(S): The murine umbilical cord mesenchymal stem cells were isolated from the female pup and cryopreserved. After the female aged, its germinal vesicle (GV) oocytes were collected and treated to weaken the zona pellucida. Its autologous umbilical cord mesenchymal stem cells were induced into granulosa cells (iGCs). The zona-weakened GV oocytes were aggregated with iGCs into iGC-oocyte complexes. Then, these complexes were cultured in growth-differentiation factor 9-containing media for 3 days. Next, they were subjected to in vitro maturation and fertilization. Presumptive zygotes were cultured for 24 hours, and the cleaved 2-cell embryos were selected for embryo transfer. MAIN OUTCOME MEASURE(S): The oocyte quality was determined by examining mitochondrial ultrastructure using transmission electron microscopy, the adenosine triphosphate content using a luminometer, and intracellular reactive oxygen species levels by confocal microscopy. The spindle organization in mature oocytes was examined by confocal microscopy. The developmental potential of oocytes was evaluated by monitoring the in vitro embryo development and the birth rate after embryo transfer. RESULT(S): Mitochondria migrated from iGCs into the GV oocyte via transzonal filopodia. The maturation rate, quality, and developmental potential of these oocytes were substantially increased. Furthermore, the birth rate after embryo transfer has been improved. CONCLUSION(S): This approach used noninvasive procedures to collect mitochondria donor cells and optimized mitochondria transfer manipulations; thus, it may have potential in ameliorating oocyte-aging-related subfertility.

Antioxidants in fertility: impact on male and female reproductive outcomes.

A couple may be considered to have fertility problems if they have been trying to conceive for over 1 year with no success. Worldwide, the inability to have children affects 10% to 15% of all couples. Subfertility can be divided into either male or female factor, or both partners can be affected. However, for some couples the cause for subfertility cannot be identified, and this is called unexplained subfertility. It is thought that oxidative stress is involved in the pathophysiology of subfertility, and antioxidants are thought to reduce the damage caused by oxidative stress. Antioxidants are widely available and inexpensive. However, there is currently little high-quality evidence to show that taking antioxidants will provide any benefit or harm for infertile couples.

MC-LR Exposure Leads to Subfertility of Female Mice and Induces Oxidative Stress in Granulosa Cells.

Health risk of human exposure to microcystin-leucine arginine (MC-LR) has aroused more and more attention over the past few decades. In the present study, MC-LR was orally administered to female mice at 0, 1, 10 and 40 µg/L for three and six months. We found that chronic exposure to MC-LR at environmental levels could stimulate follicle atresia and lead to decreased developmental follicles, accompanied by a reduction of gonadosomatic index (GSI). In line with the irregular gonadal hormone level and estrus cycles, subfertility of female mice was also confirmed by analyzing numbers of litters and pups. The in vitro study suggested that granulosa cells could uptake MC-LR and should be the target of the toxicant. Oxidative stress in granulose cells induced by MC-LR promoted follicle atresia and eventually leads to female subfertility.

Perfluoroalkyl acid contamination of follicular fluid and its consequence for in vitro oocyte developmental competence.

Perfluoroalkyl acids (PFAAs) have been shown to induce negative effects in laboratory animals and in vitro experiments. Also, PFAAs have been detected in human tissues and body fluids. The ovarian follicle constitutes a fragile micro-environment where interactions between hormones, growth factors, the oocyte and surrounding somatic cells are essential to generate a fully competent oocyte. In vitro experiments suggest that PFAAs can influence this balance, but very scarce in vivo data are available to confirm this assumption. In fact, the potential PFAA-presence in the follicular micro-environment is currently unknown. Therefore, we investigated if PFAAs are present in human follicular fluid and if their presence could be a risk factor for in vivo exposed developing oocytes. Furthermore, we compared the PFAA-distribution within serum and follicular fluid. PFAAs were analyzed by LC/MS in follicular fluid (n=38) and serum (n=20) samples from women undergoing assisted reproductive technologies (ARTs). Statistical models were used to investigate PFAA-distribution in both body fluids, to compare this behavior with the distribution of lipophilic organic pollutants and to explore the relationship between patient characteristics, ART-results and follicular fluid contamination. Perfluorooctane sulfonate (PFOS) was the PFAA found in the highest concentration in follicular fluid [7.5 (0.1-30.4) ng/mL] and serum [7.6 (2.8-12.5) ng/mL]. A new variable, Principal Component 1, representing the overall PFAA-contamination of the follicular fluid samples, was associated with a higher fertilization rate (p<0.05) and a higher proportion of top embryos relative to the amount of retrieved oocytes (p<0.05), after adjusting for age, estradiol-concentration, BMI, male subfertility and the presence of other organic pollutants as explanatory variables. To conclude, overall higher PFAA-contamination in the follicular micro-environment was associated with a higher chance of an oocyte to develop into a high quality embryo. Also, PFAAs have different distribution patterns between serum and follicular fluid compared to the lipophilic organic pollutants. Further research is of course crucial to confirm these new observations.