When pregnancy does not come
The lack of a pregnancy after a long period of unprotected intercourses configures a problem of couple infertility. From a statistical point of view the chances that the lower fertility is of male or female origin are substantially equal and in almost half the cases both coexist. Yet we still live an era of frequent aggressive diagnosis and therapy on the female side, partly the result of cultural heritage, while a male problem is sometimes considered as a last resort. So, the first thing a woman unable to obtain pregnancies must do is convince her doctor and her partner to immediately face also the other side of the problem.
On the female side, the doctor will check if the patient ovulates regularly, if there are endocrine or adnexal problems and will possibly investigate chromosomal and / or genetic status. These tests might highlight a problem suitable for surgical or medical therapy. In other cases, they will individuate some concomitant conditions having an adverse effect on fertility, typical examples are the polycystic ovary syndrome and endometriosis. Even if these conditions are not always “curable”, the awareness of the problem will direct to the most appropriate treatment strategies.
When ovulation is impaired
Partial ovulatory irregularity and occasional anovulations are almost normal and do not necessarily imply a reduced fertility. The doctor will be able to easily understand the extent of the fertility problem by monitoring several cycles with the aid of hormonal tests and / or ultrasounds. Te reproductive age of women older than 35 years and of all suspected cases should be investigated with greater care by the antral follicles count and / or by the dosage of the anti-Mullerian hormone (AMH).
The cycle irregularities physiologically tend to increase with reproductive ageing and may be an alarm bell suggesting that fertility is declining. In contrast the same irregularities are also common in very young women, often within a polycystic ovary syndrome. Most of these situations can be improved with the aid of medical therapies. Nutritional supplements with antioxidant effects may contribute effectively and sometimes are decisive. Women who suffer from serious disorders of ovulation may instead require a more complex diagnostic and therapeutic pathway and sometimes must undergo to ART.
When you take antioxidants
Even in the absence of known problems, an antioxidant support to the development of the oocyte, which lasts about 3 months, is always advisable. But, it is absolutely necessary to avoid aggressive interventions with substances with pharmacological activity. The so-called direct antioxidants such as eg. vitamins C, E and A, coenzyme Q, selenium and the like, expecially at high doses, perturbate the cellular redox balance and are likely to cause the opposite imbalance, leading to even more serious consequences.
All cells, and first of all the gametes, need a perfect osx-redox balance that can be achieved only by a normalization of cellular activity. While a balanced diet provides all the substances (several hundreds) that work together to balance cell in quantities and combinations selected by evolution, the intake of antioxidants in the form of supplements, even more if highly active, only serves to stress in reductive sense the specific chemical reactions in which each of these substances are involved. This means blocking these reactions them for the opposite imbalance. There are no magic remedies or special substances that correct all the biochemical changes.
Effective support of cellular redox equilibrium can instead be achieved by providing the cell, rather than pre-formed antioxidants, the substances that the same cell needs to produce antioxidants on its own, i.e. when and where they are needed, in the right quantities and until they are needed.
Condensyl and Procrelia are indeed based on the principle of the indirect antioxidant support, i.e. a pure nutritional intervention to sustain an efficient metabolism, and for the first time significant clinical effects on fertility have been demonstrated (Cornet et al. 2015).
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 tecnique like Intra Uterine Insemination (IUI) or more complex procedures like In Vitro Fertilization with Embryo Transfer (IVF) or Intra Cytoplasmic Sperm Injection (ICSI).
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 in terms of 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 as well important to remedy the reduced quality of the oocyte caused by the stimulation.
IVF and 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 5 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 really 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 a 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 tecniques allowing to skim the ejaculate to obtain a fraction enriched with potentially good cells. Thereafter, the final choice is made with microscopic morphological criteria.
The outcomes in terms of 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 3 months before the stimulation and the collection of the oocytes.
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 carryng the same risk factors. Similar and likely better results are now expected with Condensyl.
When the pregnancy occurs
Besides a great joy, the onset of a pregnancy carries for the women a huge responsibility for the new life she is harboring. During nine months the fetus will interact with the external world by means of the placenta and will be passively dependant on the behavour of the mother. Adapting the lifestyle and the feeding habits becames imperative.
Mother’s feeding plays a fundamental role in the development of the fetus. It must ensure an adequate income of substances and energy to grow but also key substances regulating the differentiation of the growing tissues.
Folic acid supplementation during the first trimester of pregnancy has been the first nutritional intervention to be recognised as fully clinically effective and is nowadays mandatory or strongly adviced worldwide.
This supplementation has been demonstrated as capable to prevent the occurrence of neural tube defects (e.g. spina bifida) with an efficacy of about 50%. More recent studies demonstrated similar efficacy in the prevention of autistic syndromes, which are at present a real public health alarm.
The effect of folic acid supplementation is believed tied to a improved methylation of embryo DNA that carries signals for the activation or repression of specific genes. Folic acid, favoring the recycling of homocysteine and its use for the production of bioactive methyl groups, allows a better efficiency of such processes. In addition, folic acid promotes the activity of endogenous antioxidant defences so to counteract also the other aspect of the problem, the oxidative damage.
Nevertheless, folic acid prevents these syndromes only in part and the increase of the daily dose (normally 400 micrograms) does not produce any advantage. This means that not all neural tube defects and autisms derive from folic acid deficiency and/or that supplementation with folic acid alone is not able to restore the full efficiency of DNA methylation and of antioxidant defenses. The logical consequence is that a more complete supplementation, extended to all of the metabolic pathways for the recycle of homocysteine, can increase the preventive efficacy. Although clinical demonstrations of this effect are not yet available (huge studies lasting several years are needed), all the in vitro and animal data support this idea.
Condensyl and folic acid
In addition to the usual 400 micrograms of folic acid, Condensyl contains indeed all the other substances useful for recycling of homocysteine, for the production of active methylgroups and for antioxidant defenses. It is in practice a supplementation with folic acid “fortified” at the maximum level possible today. The availability of clinical data in support of this preventive effect will require many years of study. Meanwhile, common sense suggests the obvious and large advantages over a plain coverage with folates.
According to the most recent positions of WHO, supplementation with folic acid and similar strategies must no longer be limited to the first trimester of pregnancy but should be extended to the pre-conception (at least 3 months before) and possibly also to the male partner. In fact, the changes to the profile of DNA methylation and the dysregulation from oxidative insult start already during the maturation of oocytes and sperms and a good prevention must include the phase of gametogenesi, which is called ” periconceptional” support.
Couples intentionally seeking a pregnancy should always start a preventive supplementation with folic acid or the like. This is a good reason to start the supplementation with Condensyl in both partners as soon as a pregnancy is aimed even in the absence of fertility problems.