The diagnosis of unexplained infertility is made after all standard evaluation tests in the infertility investigation return normal. Its frequency varies between 10-30% in infertile patient groups depending on the diagnostic criteria.
The diagnosis of unexplained infertility is established when there is a normal semen analysis, objective evidence of ovulation, a normal uterine cavity, and bilateral tubal patency. Although in the past, a positive postcoital test and endometrial biopsy results consistent with the menstrual cycle were required, these tests are no longer used today.
The necessity of diagnostic laparoscopy in women with unexplained infertility is controversial. Laparoscopy can provide treatment by diagnosing undetected tubal factors and endometriosis or can limit unnecessary treatments for unexplained infertility. However, in women with normal HSG (Hysterosalpingography) and pelvic examination who have no risk factors for tubal factors, laparoscopy will not provide additional explanatory information. While the effect of endometriomas (chocolate cysts) involving the ovaries and advanced endometriosis on infertility is clear, the effect of moderate disease has not been proven. Many physicians state that vaginal ultrasonography performed during the menstrual period or early post-menstrual period would be more appropriate than diagnostic laparoscopy in infertility evaluation.
Unexplained infertility includes sperm or oocyte dysfunction, fertilization, implantation, or embryo development disorders that cannot be diagnosed with standard evaluation methods. In untreated patients, the pregnancy rate per cycle is about 2-4%, or 80-90% below that of normal fertile couples (20-25%). The probability of pregnancy independent of treatment is inversely proportional to increasing female age and duration of infertility. Although most unexplained infertile couples can conceive without treatment, the decreasing conception rates over the years require them to apply for treatment. The aim of treatment is to increase monthly conception rates to the level of normal fertile couples.
Treatment Approaches
As understood from the definition, the cause of unexplained infertility is unknown. Therefore, treatment approaches are based on previous experiences and aim to increase the number of sperm and eggs encountered at a specific time. Recommended treatment methods include stimulating the ovaries with pills or injections followed by timed intercourse, IUI (Intrauterine Insemination)—where the sperm sample taken from the partner is prepared with a special method and left into the uterus by entering through the cervix—and finally, IVF (In-Vitro Fertilization) treatment.
Development of one or more eggs can be achieved with oral medications such as clomiphene citrate and letrozole. Efforts have been made to achieve pregnancy through timed intercourse, and no superiority of the methods over each other has been shown.
Studies on IUI (insemination) treatment performed with the use of ovary-stimulating injectable medications called gonadotropins report pregnancy rates of 15-18%. Considering that the pregnancy rate per cycle without treatment is 3% in those with unexplained infertility, the effectiveness of IUI treatment becomes more valuable. The pregnancy rate decreases after 3 cycles of treatment with external gonadotropins and IUI. In these cases, it would be more appropriate to suggest IVF treatment instead of insemination to couples.
Observations in IVF treatment cycles help us gain information about the causes of unexplained infertility in couples. During the procedure, sperm and oocyte are brought together, and fertilization is ensured with the microinjection method. Fertilization and early embryonic development are monitored in IVF cycles, and the embryo is placed directly into the uterine cavity (endometrial cavity) via embryo transfer. Factors related to the chromosomal structure of the placed embryo, the response of the inner lining of the uterus (endometrium), and the implantation mechanism are not fully known. The probability of pregnancy in IVF treatment varies between 40-65% depending on patient age and infertility duration.
When evaluated all together, the effectiveness of treatments in unexplained infertility is limited, and treatment only facilitates the pregnancy that can occur at a specific time. Evaluation should be done carefully, and before planning treatment, ovarian reserve tests should be performed considering the age of the couples, the duration of infertility, and previous pregnancies. Although the results obtained with IVF show a higher probability compared to other treatment methods, it indicates that other treatments may be appropriate before IVF, especially in young patients with a short duration of infertility. Couples accepting treatment should be informed about the pregnancy probabilities, risks, costs, and the process of different treatment methods to ensure they choose the most suitable one for themselves.
Op Dr İsmail Küçük / Obstetrician and Gynecologist / İRENBE