pregnant woman

When ART is needed

When medical and surgical treatments are not able to restore a fetility by natural routes it may be necessary to leverage on Assisted Reproductive Technologies (ART).

Depending on the specific clinical picture the specialist will propose a first level technique like Intra Uterine Insemination (IUI) or more complex procedures like In Vitro Fertilization with Embryo Transfer (IVF) or Intra Cytoplasmic Sperm Injection (ICSI).

Intrauterine insemination (IUI)

The IUI procedure is clinically indicated for couples in which the female partner has a good ovulatory ability and the male partner has sperm of good quality. The IUI technique is not able to remedy defects of male semen and should not be offered in the presence of male subfertility unless it is adequately treated. On the other side, it is possible to partially remedy ovulation defects by stimulating the women with the hormone FSH that will sustain the ovulation. If supra-physiological doses of FSH are used, the woman will produce more than one oocyte, and this can increase the chances that at least one is fertilized. This stimulation, although beneficial regarding effectiveness, presents potential hazards if anything goes wrong. It is indeed difficult to predict how many follicles will develop and how many of them will fertilize and multiple pregnancies may occur. Almost all the newspapers first page cases with higher order multiple pregnancies (3 or more fetuses) are coming from IUI cycles and not from in vitro fertilization (where usually only one or two embryos are transferred).

The antioxidant supplementation of women undergoing unstimulated IUI cycles can be a viable alternative to stimulation to improve oocyte quality and thus the chances of success. If rather a stimulated IUI cycle is performed, antioxidant supplementation is equally important to remedy the reduced quality of the oocyte caused by the stimulation.

In Vitro Fertilization (IVF) and Intra Cytoplasmic Sperm Injection (ICSI)

Severely impaired ovulation, with or without an associated male problem, and resistance to repeated IUI cycles are reasons why your doctor may decide to step-up to in vitro techniques such as IVF and ICSI, the latter being necessary if a severe male factor is in place. In both cases, the woman will undergo an over-stimulation with FSH to support the development of a large number of follicles. Once the follicles are mature, the oocytes are collected and fertilized in vitro. The resulting embryos are cultured in vitro for a few days, and the best developed will be transferred into the uterus. The in vitro culture of the embryo for longer times, i.e. about five days, has the advantage of allowing the sampling of some cells for the execution of genetic and chromosomal tests that will guide the selection of the best embryo to be transferred.

The two techniques, IVF and ICSI, only differ in the procedure used for fertilization.

In the case of IVF, fertilization is obtained by mixing into the test tube an aliquot of male semen with one or more oocytes. Good quality Sperm is still necessary for the fertilization to occur. If sperm is not good, a good quality oocyte, i.e. bearing little of oxidative damage, will be able to address all of its DNA repair capability on male genes and to remedy an ejaculate of modest quality.

In the case of ICSI, fertilization is achieved by injecting the chromosomes of sperm into the oocyte, which allows fertilization also if the sperms were not able to do it naturally due to e.g. low motility.  The issue of sperm quality gets minimised by sperm selection techniques allowing to skim the ejaculate to obtain a fraction enriched with potentially good cells. After that, the final choice is made with microscopic morphological criteria.

The outcomes regarding fertilization rates are pretty good as it is almost always possible to generate embryos. The problem is that the techniques of sperm selection are not able to distinguish the sperm based on the level of oxidative damage to DNA. Thus, a well-looking sperm chosen from the good fraction can still bear serious oxidative damage potentially compromising the vitality of the embryo obtained. Criticisms to the ICSI technique refer to it as a fertilization “forced” with sperm cells that natural selection would have certainly avoided. Thus, a good oocyte able to repair sperm DNA is of paramount importance. Assumed that the FSH stimulation is known to impair the oocyte quality, it became essential to support ladies undergoing ICSI cycles with a good antioxidant supplementation, possibly since at least three months before the stimulation and the collection of the oocytes.

ICSI

In case of both IVF and ICSI antioxidant supplementation may help to reduce the oocyte oxidative load with increased chances of pregnancy.

Procrelia, is the first supplement with (indirect) antioxidant activity demonstrating significant clinical advantages vs no treatment (Cornet et al. 2015). Women belonging to couples resistant to previous cycles of IVF and/or ICSI supplemented with Procrelia recorded clinical pregnancy and live birth rates that were twofold those of their controls and similar if not better than those expected in couples not carrying the same risk factors. Similar and likely better results are now expected with Condensyl.

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