Maternal spindle transfer for mitochondrial disease: lessons to be learnt before extending the method to other conditions?

Mitochondrial diseases are a group of conditions attributed to mutations of specific genes that regulate mitochondrial function. Maternal spindle transfer (MST) has been proposed as a method to prevent the transmission of these diseases and utilisation of the technique resulted in the birth of a baby free of disease in 2017 in Mexico. Potential flaws in research governance and the associated criticism emerged from the expansion of MST to provide a potentially new assisted reproductive technique to overcome infertility problems characterised by repeated in vitro embryo development arrest caused by mitochondrial dysfunction and cytoplasmic deficiencies of the oocyte. This applied technique represents a good example of the need to strike "a balance between taking appropriate precautions and hampering innovation". The purpose of this article is to explore, through a comprehensive literature search, whether and how this process can evolve from an experimental method to treat a medical condition to a standard of care solution for certain types of infertility. We argue that a number of key issues should be considered before applying the technique more broadly. These include regulatory oversight, safety and efficacy, cost, implications for research, essential laboratory skills and oversight, as well as the care needs of patients and egg donors.

The effect of in vitro fertilization on gingival inflammation according to women's periodontal status: clinical data.

OBJECTIVES: To study whether in vitrofertilization (IVF) treatment has any effect on women's preexisting periodontal status and, if pre-existing women's periodontal status has any impact on IVF outcomes, such as superovulation for multiple follicles maturation, oocyte retrieval and embryo transfer, as well as on pregnancy and its outcomes. METHODS: Sixty women aged 29 to 41 years were recruited in the study. Gingival inflammation (simplified gingival index, GI-S), plaque levels (plaque control record index, PCR), bleeding on probing (BOP) and probing depth (PD), were recorded for all participants before and after IVF. Blood tests were performed prior to IVF. RESULTS: A statistically significant increase in GI-S after IVF was observed in all women (31.9 +/- 18.7% to 61.7 +/- 23.5%), and was higher in women with gingivitis (37.1 +/- 5.7% to 77.6 +/- 6.7%). Women with periodontitis demonstrated a statistically significant increase in BOP (67.7 +/- 6.6% to 89.5 +/- 7.1%), and in the sum of probing pocket depths (from 243.8 +/- 56.2 mm to 250.5 +/- 58.3 mm). A trend for negative correlation between the number of follicles and transferred embryos and the gingival index, before and after IVF respectively, was recorded in all women. There was a similar trend with bleeding on probing after IVF in women with periodontitis. CONCLUSIONS: Periodontal clinical parameters worsened in women undergoing IVF treatment. On the other hand, a poor pre-existing periodontal status seems to be associated with poorer outcomes of IVF treatment.

Genetic and epigenetic risks of intracytoplasmic sperm injection method.

Pregnancies achieved by assisted reproduction technologies, particularly by intracytoplasmic sperm injection (ICSI) procedures, are susceptible to genetic risks inherent to the male population treated with ICSI and additional risks inherent to this innovative procedure. The documented, as well as the theoretical, risks are discussed in the present review study. These risks mainly represent that consequences of the genetic abnormalities underlying male subfertility (or infertility) and might become stimulators for the development of novel approaches and applications in the treatment of infertility. In addition, risks with a polygenic background appearing at birth as congenital anomalies and other theoretical or stochastic risks are discussed. Recent data suggest that assisted reproductive technology might also affect epigenetic characteristics of the male gamete, the female gamete, or might have an impact on early embryogenesis. It might be also associated with an increased risk for genomic imprinting abnormalities.

Fertility drugs and gynecologic cancer.

Fertility drugs (FD) are spreading worldwide fast and therefore many studies have reviewed the possible association between the use of these drugs and cancer. Since the drugs used for ovulation induction during in vitro fertilization (IVF) like hCG, hMG, rFSH increase the levels of gonadal hormones, concerns have grown regarding the risk of developing cancer in breast, ovary, endometrium, and other target organs. In this review, we discuss a number of different studies published in recent years that show no association between the use of these drugs and most cancers.

Serum and follicular fluid leptin levels are correlated with human embryo quality.

This prospective study was undertaken to reassess the prognostic value of leptin during critical stages of in vitro fertilization-embryo transfer (IVF-ET) and address its role in the functional staging of assisted reproductive technologies at the level of embryo quality. Serum and follicular fluid samples of 100 selected women undergoing the long IVF-ET protocol were collected for leptin and embryo quality determination. The highest serum leptin concentration (52.11 +/- 4.27 ng/ml) was observed on ovum pick up day, while follicular fluid leptin was higher than all serum samples examined (62.59 +/- 5.73 ng/ml). Serum leptin above 59.48 +/- 7.6 ng/ml was associated with 'poor' embryo quality and above 56.87 +/- 5.52 ng/ml with pregnancy failure. Elevated leptin concentrations were associated with reduced ovarian stimulation and response, follicle maturation, embryo quality and pregnancy success. Our findings suggest that leptin modulates embryo quality and may serve as a sensitive marker of IVF outcome.

The effect of valacyclovir treatment on natural killer cells of infertile women.

PROBLEM: The aim of this study was to investigate the effect of valacyclovir treatment on natural killer (NK) cell concentration in the peripheral blood of infertile women. METHOD OF STUDY: Peripheral blood NK cell concentration of 104 non-pregnant women with a history of infertility was determined by flow cytometry. The controls were 14 fertile non-pregnant women. A cohort of 42 out of 104 women--whose NK cell levels were 175/microL or higher--was prospectively studied for the presence of HSV-1, 2, VZV, cytomegalovirus, HHV-6, HHV-7 and HHV-8 DNA in the peripheral blood and was orally administered valacyclovir (open label study). RESULTS: Herpes virus DNA was detected in 64.3% of the 42 women examined. Prior to valacyclovir treatment mean NK cell concentration in herpes-negative group was statistically higher from control group but lower from herpes positive group (P = 0.0007, ANOVA). Following valacyclovir treatment the mean NK cell concentration was statistically decreased in all studied women (P = 0.000453), in herpes-negative (P = 0.01622) and in herpes positive group (P = 0.0056). Sufficient decrease was observed in 31 (73.8%) of 42 women who received the drug. CONCLUSIONS: Valacyclovir treatment is associated with a decrease of NK cell levels in most of the women with a history of infertility.