A surprising link with unexplained infertility: a possible Covid-19 paradox?

Unexplained infertility represents about 22–28 percent of infertility causes.
The diagnosis is based on the exclusion of common causes using standard fertility investigation.


Over the years, the causes of unexplained infertility or subfertility have been identified in pre-existing associated pathologies, such as alterations of the immune system, thyroid dysfunctions, and coagulopathies.

Studies regarding the influence of psychological factors on the development of infertility highlighted that spontaneous pregnancies following adoption or the decision to remain childless are absolute exceptions. The link between stress and infertility in humans is still unclear. For many women, the effect of infertility and the subsequent medical therapy represents a considerable emotional stress.

Accordingly, the relationship between the environment and the reproductive capacity has been proved to have a direct correlation.
Previous work demonstrated that stress is associated with changes in eating habits and exercise, resulting in a complicated spectrum of reproductive disorders.

However, the potential impact of the interrelationship between stress and frequency of sexual intercourse on reproductive efficacy was not sufficiently described.

The low frequency of sexual intercourse in the couple is often not mentioned during the anamnestic investigation, mostly because this issue is a source of frustration and shame.

Psychological stress, physical fatigue, lack of adequate time, and geographical distance represent the main determinants of low frequency of sexual intercourse. Therefore, there is a considerable proportion of couples with unexplained infertility that is treated with assisted reproduction techniques, who would have been able to naturally conceive a baby by simply increasing their sexual activity.

On March 10-2020, Italy became the first democratic country since World War II to impose a national lockdown. In few days, the outbreak spread from a northern crisis to a national one. Restriction measures are imposed to stay home and seek permission for essential travel.

Many companies have started smart working for their employees. At the same time, both the most accredited national and European scientific societies for reproductive medicine and the National Transplant Center, the institute that is responsible for the control of the Centres for ART (PMA) in Italy, have arranged to postpone the cycles of ARTs, waiting for the end of the coronavirus pandemic.

In order to assess the potential impact of insufficient sexual activity on infertility, the group studied whether recent COVID-19-releated lockdown in Italy had any effect on conception ability of couples with unexplained infertility. The scientists included in the study 50 couples with unexplained infertility. In these couples, medically assisted procreation techniques were temporarily suspended because of the lockdown, as imposed by the Italian Institute of Health. Interestingly, they found that 14% of the couples conceived naturally after years (average 2 ± 0.7 years) of infertility.

All the seven couples were contacted by phone, and all confirmed a significant increase in sexual activity, from an average of 2/month to two to three times/week (p < 0.001). They all stated that the longer time spent together at home contributed to the increase of their sexual activity.

It has to be noted that the spontaneous pregnancy rate is so significantly close to that in the literature of unexplained infertility (14% vs 15%, p = 0.9).
Therefore, lockdown and smart working during the pandemic have increased the frequency of sexual intercourse and could have unmasked the real cause of infertility or unexplained subfertility in these couples. It seems unlikely that a reduction of psychological stress would have contributed to the success to the natural conception of a baby in these seven couples, because of the extremely high stress levels felt in Italy during these months, in which more than 25,000 deaths due to COVID-19 were reported.

The team observation seems to suggest that insufficient sexual activity should always be ruled out in couples referring to reproductive centers for fertility issues. It is interesting to note that couples confined to home, naturally increase the amount of sexual intercourse.

Clinicians probably should resist to the temptation to begin an active treatment and not immediately propose medical treatments in these couples. The real impact of insufficient sexual activity on unexplained infertility warrants further clarification in larger studies.

What do you think about “Increase the frequency of sexual intercourse”?

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Complex structure at the tip of the sperm tail

New studysperm tail led to the discovery of a novel, complex structure at the tip of the sperm tail that has never been seen before.

Since sperm motility and morphology are determinants of male fertility, understanding the functional role of the TAILS complex may have clinical implications relating to male infertility and contraception.

Why choose IVF? 10 + 1 reasons

Why choose IVF? 10 + 1 reasons

IVF is likely to be recommended for the following fertility problems:

Why choose IVF1. Damaged or blocked fallopian tubes, which stop the sperm from reaching the egg.
2. Ovulation disorders, which result in fewer eggs available for fertilization.
3. Premature ovarian failure (loss of normal ovarian function before the age of 40).
4. Endometriosis, which affects the function of the ovaries, uterus and fallopian tubes.
5. Fibroids (benign tumors which grow beneath the outer layer of the uterus (subserosal), inside the muscular wall of the uterus (intramural), or inside the uterine cavity (submucus) and can cause infertility.
6. Previous tubal sterilization or removal.
7. Male infertility, including poor sperm quantity, poor sperm mobility, or poor sperm quality (increased percentage of abnormalities in sperm size and shape), which reduce the chance of fertilization.
8. Advanced reproductive age.
9. Unexplained infertility, where, in spite of the complete evaluation for common causes, the cause of infertility has not been found.
10. A genetic disorder. If you or your partner is at risk of passing on a genetic disorder to your child, then a procedure that involves IVF called Preimplantation Genetic Diagnosis (PGD) can be performed in the Mediterranean Fertility Institute.
11. Fertility preservation for cancer or other health conditions. Women can freeze (cryopreserve) her eggs in an unfertilized state for later use or her eggs can be fertilized and frozen as embryos for future use.

Unexplained Infertility: Treatment for Fewer Side Effects

Infertility is a significant global problem affecting 1:7 worldwide. An estimated 24% of couples had no detected conception within 12 and 24 months of unprotected intercourse on a nation-wide representative sample of couples from the general population. Unexplained infertility is one of the most frequent infertility diagnoses given to women, encompassing up to approximately 30% of all cases.


Women with unexplained infertility are commonly treated with drugs for ovarian stimulation.

Unexplained infertility refers to couples who fail to conceive, even though the female ovulates normally, has no obvious abnormalities in the reproductive tract, and the male is producing an adequate number of motile sperm. Nowadays, there are plenty of infertility treatments available, however many assisted reproduction techniques like IVF are very expensive and not often covered by insurance; therefore IVF is an option less commonly offered.

Women with unexplained infertility are commonly treated with drugs for ovarian stimulation. During this procedure the ovaries release an egg and sperm is directly inserted into the uterus. This is a quite successful treatment and definitely less costly. Letrozole, gonadotropins and clomiphene citrate are the drugs most commonly used for ovarian stimulation.
Unfortunately, medication for ovarian stimulation has its side effects and can be complicated by ovarian hyperstimulation syndrome, which results in multiple pregnancies with increased risk of preterm birth. The challenge is to determine which medication is best at achieving and maintaining pregnancy while reducing multiple pregnancies.

In a recent study, scientists assessed the frequency of multiple pregnancies among women with clinical pregnancies. Women age 18 to 40 who were ovulating and had at least one Fallopian tube were treated with letrozole, gonadotropins or clomiphene for up to four cycles, comparing the outcome for the three drugs. According to the study, ovarian stimulation with letrozole resulted in significantly lower frequency of multiple pregnancies, but also a lower frequency of live births, as compared with gonadotropins, but not as compared with clomiphene. Therefore, scientists concluded that clomiphene citrate is the most appropriate means to stimulate ovulation in unexplained infertility treated with intrauterine insemination (IUI).

Would clomiphene, as the least invasive treatment, be your first option among other alternatives for unexplained infertility treatment?

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