ART (Artificial Reproductive Technology) is virtually legalized in Germany, with costs covered by health insurance companies. When there is an urgent desire to have children, hardly anyone wants to critically scrutinize the methods used and doctors hardly want to unsettle anyone.

ART is mainly used in performance-oriented societies. The ideas of such societies can be summarized briefly: the distribution of desired goods, such as power, income, prestige and wealth, should be based on the individual’s performance. As a rule, mothers hope that their children will be able to participate positively in this later on.

• ART
• Sperm
• Egg cell
• Complex process

Matthias Wenderlein J (2024) ART and Sperm Selection by Egg Cell as a Complex Process. Med J Obstet Gynecol 12(2): 1187.

ART (Artificial Reproductive Technology) is virtually legalized in Germany, with costs covered by health insurance companies. When there is an urgent desire to have children, hardly anyone wants to critically scrutinize the methods used and doctors hardly want to unsettle anyone.

ART is mainly used in performance-oriented societies. The ideas of such societies can be summarized briefly: the distribution of desired goods, such as power, income, prestige and wealth, should be based on the individual’s performance. As a rule, mothers hope that their children will be able to participate positively in this later on.

This may seem rather abstract at first. But anyone who has worked in obstetrics long enough will be confronted with it. Every newborn should have the best possible starting conditions from birth. This is why pregnancies and births are monitored more and more closely. The desire for the “perfect” child as a rule also applies to women who want to use ART.

The latter rarely know that the egg itself wants to make the best possible sperm selection during conception. Evolution has determined this for optimal results. This selection will include sustainable performance aspects, such as minimizing the risk of morbidity. This would be of social relevance.

Women who classify the above aspects as irrelevant when they want to have children are not the issue here.

With IVF, approximately two out of three women become pregnant after four treatments. With ICSI, the total pregnancy rate after two treatments is around 50%. The average birth rate per ICSI treatment cycle is around 15 % or a maximum of 20 %. 2021 the birth rate per IVF transfer was 22 %. Is this large difference due to non-optimal blastocysts? ART focuses on non-optimal implantation conditions.

The rather disappointing ART results are rarely associated with a lack of active selection of suitable sperm by the mature egg. This would be urgently indicated due to the following risks.

Children after artificial insemination are at risk of premature vascular aging. Clinically, this manifests itself in more heart attacks and strokes. Half of the general population is affected by CHD morbidity from middle adulthood onwards.

Approximately half of the risk of dying from CHD increases with age. Increased blood pressure occurs in one in six ART adolescents. This is very rare in those with normal conception.

An example of this is a systematic literature search [1], which analyzed 15 evidence-based studies from January 2019 to January 2020. Hypertension and CHD were found significantly more frequently in IVF/ICSI patients. General vascular dysfunction is triggered by premature vascular ageing. In addition, there is the well-known medical insight that people are as old as their vascular system.

But oncological diseases are also more common after embryo transfer. This includes a higher risk of leukemia from childhood onwards. This is the result of a Danish cohort study [2], with 8.5 million children and a follow-up of seven years. The low absolute disease rates can be classified as “acceptable”. But an increasing risk is to be expected with longer observation. There is too little interest in all this among lay people and doctors.

The author’s interest in reproductive medicine is essentially based on his experience in two university outpatient clinics for 35 years. Women under prolonged stress of all kinds wanted regular cycles again as before without stress and those who wanted to have children wanted regular ovulations in addition. The first diagnostic step was usually to take basal body temperature curves for 2 to 3 months. If a corpus luteum insufficiency was recognized in the course of these curves, then progesterone substitution was rationally comprehensible for the women and they recognized the success in the course of the curve. The women’s own initiative and personal responsibility were therefore paramount. They should recognize that ovarian function is influenced by external factors. This is hardly necessary for ART activities. This is in line with today’s consumer mentality with little personal responsibility.

Reduced fertility due to stress should not be ignored. After all, a very stressed mother is not a good basis for the newborn and its physical and psychosocial development from birth. This was generally taken as important information by women who wanted to have children.

What does this have to do with ART? The author looked after women who had a spontaneous pregnancy after IVF pregnancy and who came to the outpatient clinic after giving birth. This group had one thing in common: less constant stress than in earlier times.

In women with prolonged amenorrhea, especially in anorexia nervosa, hardly any hormone diagnostics are primarily necessary, whereas ART requires a lot. After ruling out clinical causes, checking the genital status by means of a clinical examination (with microscopic assessment of vaginal cells in a native preparation under estrogen aspects) and sonography, a detailed medical history was taken. In the case of a stress history, the amenorrhea episode was explained to the women as a sensible reaction of the ovaries. Under such conditions, evolution did not want a pregnancy, as it was too risky for the pregnant woman and the unborn child. This applies in particular to male foetuses with the risk of telomere shortening [3], and thus the risk of faster ageing. Emergency and wartime amenorrhea have been known for a long time. With insight and acceptance, very stressed women wanted to clarify beforehand what they could do against the permanent stress instead of quickly realizing their desire to have children. With ART, such considerations are rarely made; actionism for success is too often the motto.

No lecturer wanted to take on the subject of embryology for medical students and so lectures on the subject became a “standing order” for the author. One teaching focus was on the activities of egg cells, which are quite “picky” and only want to select one sperm from millions of sperm cells. ART has almost contradictory ideas about this. Pregnancy should be achieved as quickly as possible, omitting the complex selection criteria of the mature egg cell.

If implantation does not take place during reproductive medicine procedures, this is equated with treatment failure, whereby the lack of implantation is not sufficiently associated with the inadequate selection of sperm by the mature egg cell. The resulting blastocytes are not sufficiently assessed from a sustainable quality perspective.

What disturbs implantation processes is not described in detail here. This also applies to immunological processes and diseases that impair fertility, e.g. systemic oncological therapies.

The latter can disrupt the luteal phase and thus the formation of the endometrium ready for nidation. Blastocyst implantation is essentially regulated by the functions of uterine natural killer cells. The latter represent the largest proportion of immune cells in the endometrial secretion phase. They have a kind of guardian function. Apparently, only blastocysts of a quality predetermined by evolution should be released for implantation. The goals of the killer cells would then correspond to the wishes of most women: to give birth to a healthy child in the best possible way.

Regulatory T cells are relevant for the development of maternal immune tolerance towards the embryo. This is easy to convey in fertility counseling: what does not fit together should not develop. The problem is known from repeated miscarriages.

Natural killer cells intrauterine or in the endometrium represent an innate immune response: they can have an immediate cytotoxic effect and the blastocyst cannot develop further.

The various immune cell interactions in the endometrium are not discussed here. As a consultant, the information is sufficient: uterine natural killer cells play a meaningful role in determining successful implantation.

The nidation window is certainly limited in time during the luteal phase of the cycle. The knowledge about this cannot be validated and used in clinical tests. This is hardly surprising given the clinical experience that a single missed combined pill can lead to pregnancy.

Anyone who has worked with basal body temperature curves is surprised by pregnancies that could not have occurred. This means that there are apparently larger time windows for clinical pregnancies and that these can occur under “suboptimal” endometrial conditions.

The topic interests ART via gene expression analysis. Research into the synchronization of embryo development and endometrial status serves to determine the optimal time for embryo transfer. The results are so sobering that the routine use of endometrial gene expression analysis can hardly be advised.

Automated ICSI injections, i.e. with robots, do not result in higher pregnancy rates [4-6]. What was successful in rodents is not transferable to humans. This is the result of a study with 84 post-matured egg cells. 37 out of 40 (92.5%) of the eggs survived the robotic injection. If this was done by embryologists, then 44 out of 46 (95.7 %) were fertilized. 13 out of 14 ICSIA-injected eggs were fertilized. The figure for embryologists was 16 out of 18. ICSIA, only half were of “good quality”. Automation studies confirm the problem [7]: the identification of a suitable sperm by the mature egg is still pending in ART. This is the issue here.

In reproductive medicine, there are many contributions on the physiology of implantation processes. Blastocytes as a complex phenomenon are often in the foreground. The even more complex topic of the prior selection of the suitable sperm by the fertilizable egg would be ethically obligatory for ART. Out of a total of 20 to 60 million sperm per 1 ml of coagulum, only a few are suitable for the development of an intact embryo/ fetus. This is not a hypothetical statement if ART children are observed into adulthood. ART vascular risks have already been mentioned above. The author worked at the clinic where the first IVF child was born in Germany. This was the success of a veterinarian with a lot of IVF experience in farm animals with quite limited lifespans. At that time, the question of IVF risks was not raised when life expectancy in humans was considerably longer. In addition, the cloned sheep Dolly was a “great” success. The animal only lived half as long as its conspecifics and had to be euthanized due to many serious morbidities. It was therefore riskily simplified.

The sperm migration to the mature egg cell takes just under 1 hour. Sperm cells must be very active on this journey of approx. 15 cm in length. For every centimeter covered, around 600 sperm tail strokes are required to make targeted progress. So only very vital sperm will manage this race with millions of “competitors”. Is this associated with the quality of their genetic make-up? Which chromosomes are responsible for the speed of the sperm threads and at the same time intelligent, goal-oriented movement? Evolution has probably developed the concept that the best sperm should unite with the egg. ART should be interested in the definition of “best sperm” for evolution.

In order for sperm to find their way to the mature egg quickly and not “buzz around” in circles, an “orienting” secretion (including special sugars) is secreted in the cervical canal or from the surface of the cervix, which sperm should recognize quickly.

The egg itself can also secrete “attractants” from its membrane. Of the sperm “attracted” in this way, the egg cell selects the one that appears suitable and the relatively tough egg cell membrane is only opened for this sperm. The penetration of the egg cell also marks the beginning of the resealing of the egg membrane.

This can be interpreted “mechanistically” as avoiding “over- fertilization”, i.e. no penetration of more sperm. The assumption that the egg cell only classifies this one sperm as suitable is more differentiated. The cell nuclei of sperm and egg are therefore separated according to strict selection criteria in order to form 23 pairs of chromosomes.

This is known from the more highly developed animal kingdom, i.e. it is not a “random” but a targeted fertilization selection. In textbooks on human egg cells, various mechanisms are described on the basis of studies on how the one sperm that appears to be the right one is selected from millions of sperm.

The above simple descriptions are sufficient to require ART to consider complex selection mechanisms in the appropriate sperm selection. The egg cells should retain the sperm selection options provided by evolution. As long as this has not been clarified, many ART activities would have to be classified as model studies from an ethical point of view.

ART characterized by “sperm dominance” in thought and action Is it unconsciously or “semi-consciously” experienced as “offending” that evolution has endowed the mature egg cell with many abilities to select only one sperm cell out of millions that it deems suitable for optimal embryo/fetal development? Can ART actors ignore this? This is not a matter of ideology, but of clinical-pragmatic goals: the ART “product” must be qualitatively comparable to that after spontaneous conception. With IVF activities for around 50 years and over 5 million ART births worldwide, it would be possible to compare their morbidity costs with those after spontaneous conception. This should be done on a gender basis.

Here is a clinical digression. In the case of very immature twins with comparable birth weight and clinical status, girls have better chances of survival than boys in the same situation. This is not discussed enough in studies and is almost a taboo. In the Bible, Adam was created first and then Eve. In the Koran, it is the other way around and in line with biology. Classifying Y as a “failed” X may come as a surprise. Life is possible with only one X, but not with only Y without an additional X. Almost two thirds of intelligence is localized on X, semivalidated by the Turner syndrome.

This final digression refers indirectly to ART, which should  think and act more “feminine” (with XX, decisions are made more deliberately in both hemispheres of the brain). Evolution has given egg cells active options for sperm selection. ART assumes “passive” egg cells - with risks for ART pregnant women and children.

Today, ART achieves almost 100% conception success, but only about 20% result in the birth of a child, with uncertain health risks. The vast majority of ART blastocytes obviously do not meet the quality criteria set by evolution. ART activities relate too much to better implantation conditions. IVF experience has been available for 50 years, with over 5 million ART births worldwide. These should be compared with people without ART in terms of health and performance in the long term, i.e. conception according to evolutionary specifications.

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