Unexplained infertility

Infertility in most couples may be attributed in abnormalities in the male or the female reproductive system and sometimes in both. However, in around 30% of the couples that cannot conceive and seek infertility treatment, the reason for the infertility is unknown.

Patients with unexplained infertility are divided in two groups. One group includes patients with no apparent problem and yet cannot conceive. The other group includes patients with some problem, which is difficult to be detected. A woman is considered to suffer from unexplained infertility when her ovulation is normal, her fallopian tubes free of fibrosis or endometriosis and has regular intercourse especially at ovulation (10th – 14th day of the cycle) for a year without pregnancy. The partner, respectively, should have a normal sperm production. Ten per cent (10%) of all couples with infertility suffer from unexplained infertility although this percentage varies according to the effectiveness of the tests or the type of the technology used. However, the percentage of unexplained infertility is decreased, as the screening gets more detailed.

Possible causes of unexplained infertility.

  • Fallopian abnormalities: An indiscernible disorder in the mechanism with which the fibria capture the ovum after the ovulation and lead it to the uterus might be present.
  • Luteal phase defect: Luteal is the phase of the cycle after ovulation. If, for some reason, there is a deficiency, it is considered to be luteal phase defect. The corpus luteum produces progesterone, a hormone essential for the preparation of the endometrium to accept the fertilized egg (ovum). The presence of luteal phase defect is checked either by determining the level of progesterone in the blood performed in various days after ovulation, or through an endometrium biopsy.
  • Infections: Some infections are responsible for certain cases of unexplained infertility like mycoplasma or chlamydia which although they are difficult to be detected, they cause infertility.
  • Immunological factors: It is possible that the female immune system may react to the sperm by destroying it, immobilizing it or causing it to agglutinate. In addition, some women develop an immunological reaction to the outer shell of the egg blocking the sperms.
  • Inability of the sperm to penetrate the egg: Although some men have a normal sperm count, it cannot fertilize the egg. The only diagnosis for this case is in vitro fertilization and Intracytoplasmic sperm injection (ICSI).
  • Uterus: Some women present abnormalities in the endometrium which prevent the implantation of the fertilized egg. A vaginal ultrasound may confirm the diagnosis. The endometrium of a few infertile women remains extremely thin, probably due to insufficient blood supply or due to insufficient oestrogen receptors in the endometrium cells. This remains a difficult problem to be dealt with and the treatment remains basically simple by prescribing low doses of aspirin, or high doses of oestrogen.
  • Abnormal eggs: A very small percentage of unexplained infertility has to do with the production of abnormal eggs. These may be disfigured in shape or have chromosomatic disorders (especially in older women).
  • Unruptured follicles (Luteinized Unruptured Follicles LUF Syndrome): In some cases, although the eggs are normally produced and matured they remain in the follicle because they cannot disrupt it.
  • Psychological factors: Studies on various groups of infertile couples have shown an inability of agreement on the significance of the psychological factor as a cause for infertility. Emotional disorders play, no doubt, a role which is justified by the fact that the whole hormonal cycle with its delicate regulation is controlled by the brain. However, this is an area in need of further investigation.

Treatment of unexplained infertility

There are a number of ways to treat couples with unexplained infertility, and they depend on maternal age and the longetivity of the infertility. Generally, the initial methods of treatment are simple and mild and if these prove unsuccessful more complicated types of treatment are preferred.
The first line of treatment is expectant management, during which the couple has intercouse on specific dates of the cycle. At the same time mild medication for ovulation induction with clomiphene citrate or aromatase inhibitor, may be administrered. Sperm insemination, with or without ovulation induction and in vitro fertilization (IVF) are the next steps in trying to achieve a pregnancy.
Three large studies have been published investigating the difference in results between insemination with ovulation induction and IVF [1, 2, 3]. No statistically significant differences were observed in any of the studies between the two techniques in couples of unexplained infertility.
Furthermore, the chances of multiple pregnancy are the same after both technique. Finally, the cost of insemination can be as low as one eightth of that of IVF, the use of hormones is milder and, generally, it poses less physical and phychological strain on the woman.
In our Centre we used the new, improved method for insemination, intrauterine tubeperitoneal sperm injection (IUTPI). The mode of insemination has shown to reach success levels of 30%.

  1. Pandian Z, Gibreel A, Bhattacharya S. (2012). In vitro fertilization for unexplained subfertility. Cochrane Database Syst Rev. CD003357.
  2. Ray A, Shah A, Gudi A, Homburg R. (2012). Unexplained infertility: an update and review of practice. Reprod Biomed Online. 24(6): 591-602.
  3. Custers IM, König TE, Broekmans FJ, Hompes PG, Kaaijk E, Oosterhuis J, Mochtar MH, Repping S, van Wely M, Steures P, van der Veen F, Mol BW. (2011). Couples with unexplained subfertility and unfavourable prognosis: a randomized pilot trial comparing the effectiveness of in vitro fertilization with elective single embryo transfer versus intrauterine insemination with controlled ovarian stimulation. Fertil Steril. 96(5): 1107-1111.


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