Double HCG trigger improves recovery of oocytes in women with a paucifollicular response to ovarian stimulation: A pilot study.

OBJECTIVE: To examine whether adding a second HCG trigger, 12.5 h after the first (36.5 h before ovarian puncture), can facilitate recovery of oocytes in women with a paucifollicular response to ovarian stimulation. METHODS: A total of 85 women aged 35-42 years, with a paucifollicular response to ovarian stimulation and who had experienced a total failure of oocyte recovery after the standard HCG ovulation trigger 36.5 h before ovarian puncture, were subsequently treated by the same protocol but with the addition of a second HCG trigger 12.5 h later. The recovered oocytes were inseminated by intracytoplasmic sperm injection (ICSI) and all available embryos were transferred 3 days later. RESULTS: The double trigger enabled recovery of cumulus oophorus cells from most of the follicles in the women who experienced failure of total recovery of oocytes after a single trigger. Fifteen patients became pregnant, and no signs of ovarian hyperstimulation syndrome were observed. Nine women delivered a healthy child. CONCLUSION: In women aged 35-42 years with a paucifollicular response to ovarian stimulation, a double HCG trigger appears to improve the rate of oocyte recovery. The conclusion of this pilot study needs to be confirmed by larger prospective trials.

Assessing the testicular sperm microbiome: a low-biomass site with abundant contamination.

RESEARCH QUESTION: The semen harbours a diverse range of microorganisms. The origin of the seminal microbes, however, has not yet been established. Do testicular spermatozoa harbour microbes and could they potentially contribute to the seminal microbiome composition? DESIGN: The study included 24 samples, comprising a total of 307 testicular maturing spermatozoa. A high-throughput sequencing method targeting V3 and V4 regions of 16S rRNA gene was applied. A series of negative controls together with stringent in-silico decontamination methods were analysed. RESULTS: Between 50 and 70% of all the detected bacterial reads accounted for contamination in the testicular sperm samples. After stringent decontamination, Blautia (P = 0.04), Cellulosibacter (P = 0.02), Clostridium XIVa (P = 0.01), Clostridium XIVb (P = 0.04), Clostridium XVIII (P = 0.02), Collinsella (P = 0.005), Prevotella (P = 0.04), Prolixibacter (P = 0.02), Robinsoniella (P = 0.04), and Wandonia (P = 0.04) genera demonstrated statistically significant abundance among immature spermatozoa. CONCLUSIONS: Our results indicate that the human testicle harbours potential bacterial signature, though in a low-biomass, and could contribute to the seminal microbiome composition. Further, applying stringent decontamination methods is crucial for analysing microbiome in low-biomass site.

Ovarian Aging: Molecular Mechanisms and Medical Management.

This is a short review of the basic molecular mechanisms of ovarian aging, written with a particular focus on the use of this data to improve the diagnostic and therapeutic protocols both for women affected by physiological (age-related) ovarian decay and for those suffering premature ovarian insufficiency. Ovarian aging has a genetic basis that conditions the ovarian activity via a plethora of cell-signaling pathways that control the functions of different types of cells in the ovary. There are various factors that can influence these pathways so as to reduce their efficiency. Oxidative stress, often related to mitochondrial dysfunction, leading to the apoptosis of ovarian cells, can be at the origin of vicious circles in which the primary cause feeds back other abnormalities, resulting in an overall decline in the ovarian activity and in the quantity and quality of oocytes. The correct diagnosis of the molecular mechanisms involved in ovarian aging can serve to design treatment strategies that can slow down ovarian decay and increase the quantity and quality of oocytes that can be obtained for an in vitro fertilization attempt. The available treatment options include the use of antioxidants, melatonin, growth hormones, and mitochondrial therapies. All of these treatments have to be considered in the context of each couple's history and current clinical condition, and a customized (patient-tailored) treatment protocol is to be elaborated.

The Effect of GH Administration on Oocyte and Zygote Quality in Young Women With Repeated Implantation Failure After IVF.

Growth hormone (GH) has been shown to improve implantation and live birth rates in women of >40 years of age treated by in vitro fertilization (IVF). This effect was initially attributed to a GH effect on oocyte quality, but later studies showed that GH can also improve uterine receptivity for embryo implantation. As to younger women with previous failures of embryo implantation after IVF, data reported in the literature are ambiguous. This retrospective study focused on this latter category of women, comparing the numbers and morphological appearance of oocytes recovered from women with two previous IVF failures, aged between 30 and 39 years and treated with GH, with a comparable group of women without GH treatment. These results were complemented with the analysis of morphological markers of zygote and embryo quality and IVF clinical outcomes in both groups. The oocytes, zygotes and embryos from women treated with GH showed better morphological scores, and their uterine transfer resulted in more implantations, pregnancies and live births, as compared with the untreated group. It is concluded that the improvement of IVF outcomes in women with previous repeated IVF failures by exogenous GH administration is, at least partly, related to an increase in oocyte developmental potential. The statistically evident improvement of oocyte and embryo quality is the main finding of this study. Its weakness is its retrospective nature.

Luteal Phase in Assisted Reproductive Technology.

Luteal phase (LP) is the period of time beginning shortly after ovulation and ending either with luteolysis, shortly before menstrual bleeding, or with the establishment of pregnancy. During the LP, the corpus luteum (CL) secretes progesterone and some other hormones that are essential to prepare the uterus for implantation and further development of the embryo, the function known as uterine receptivity. LP deficiency (LPD) can occur when the secretory activity of the CL is deficient, but also in cases of normal CL function, where it is caused by a defective endometrial response to normal levels of progesterone. LPD is particularly frequent in treatments using assisted reproductive technology (ART). Controlled ovarian stimulation usually aims to obtain the highest number possible of good-quality oocytes and requires the use of gonadotropin-releasing hormone (GnRH) analogs, to prevent premature ovulation, as well as an ovulation trigger to achieve timed final oocyte maturation. Altogether, these treatments suppress pituitary secretion of luteinizing hormone (LH), required for the formation and early activity of the CL. In addition to problems of endometrial receptivity for embryos, LPD also leads to dysfunction of the local uterine immune system, with an increased risk of embryo rejection, abnormally high uterine contractility, and restriction of uterine blood flow. There are two alternatives of LPD prevention: a direct administration of exogenous progesterone to restore the physiological progesterone serum concentration independently of the CL function, on the one hand, and treatments aimed to stimulate the CL activity so as to increase endogenous progesterone production, on the other hand. In case of pregnancy, some kind of LP support is often needed until the luteal-placental shift occurs. If LPD is caused by defective response of the endometrium and uterine immune cells to normal concentrations of progesterone, a still poorly defined condition, symptomatic treatments are the only available solution currently available.