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This issue of the journal is dedicated to exploring the potential underlying causes and treatments of unexplained infertility. Unexplained infertility is defined as the non-occurrence of conception after 12 months of unprotected intercourse without an identifiable cause. Before unexplained infertility can be diagnosed, other causes for infertility must be excluded, including anovulation, blocked fallopian tubes, or significant impairment of semen parameters, as conception requires release of an oocyte and a functional conduit to meet the spermatozoa.
To further explore more subtle perturbations in gamete function Professors Aitken and Homer discuss the role of the sperm and the oocyte in unexplained infertility. Dr. Kamath discusses whether direct visualization of the tubes and the uterus with laparoscopy and hysteroscopy is warranted to document full function.
After investigation of infertility, moving into the clinical management of infertility, couples with an identifiable cause may be helped with a causal treatment. The majority of anovulatory women will usually conceive after ovulation induction, assuming all other tests are normal. Significant male factor infertility is addressed by the identification of a normal spermatozoon and its injection into the oocyte by intra-cytoplasmic sperm injection (ICSI). Significant anatomical abnormalities of the uterus and the fallopian tubes may be corrected surgically, and blocked fallopian tubes and clinically significant endometriosis can be bypassed with in-vitro fertilization (IVF).
If unexplained infertility is 'diagnosed', management should rely on its prognosis. Prior to attempting to conceive, whatever the treatment proposed, all couples should be encouraged to address any adverse lifestyle factors, or concurrent medical treatment, that may limit conception or adversely influence pregnancy outcome. Prognosis for natural conception decrease with higher female age and longer duration of infertility, but increases if there are previous pregnancies, including miscarriages. If the potential for natural conception chances in the ensuing 12 months are higher than 30 to 40%, expectant management may be appropriate.  However, when natural conception chances are below 30%, intervention is warranted. As in unexplained infertility an underlying cause has not been identified, the treatment is focused on increasing the conception chance per cycle. Intra-uterine insemination, often combined with mild controlled ovarian stimulation, improves timing of conception and brings the sperm closer to the oocyte. Ovarian hyperstimulation aims to increase the number of oocytes, which increases the conception chances, however at the cost of a risk of multiple pregnancies, and hence follicles should only be triggered for release with 2 or 3 dominant follicles. Finally, IVF bypasses potential barriers that limit the egg and sperm meeting, increase chances as multiple oocytes are utilized, but keeps multiple pregnancies to a minimum through single embryo transfer. Drs Wang and Abdallah show that a prognosis guided management of unexplained infertility is both safe and cost-effective.
Finally, it is important to realize that the better we understand infertility, the less the contribution of 'unexplained' infertility will be. The contributions of Drs. Dreyer and Hunt demonstrate that endometrial receptivity, reversable tubal obstruction with debris and myometrial contractility all might play a role in infertility for couples in whom the routine fertility work-up has not readily identified a cause.
24 November 2020 (online)
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- 2 Hunault CC, Habbema JD, Eijkemans MJ, Collins JA, Evers JL, te Velde ER. Two new prediction rules for spontaneous pregnancy leading to live birth among subfertile couples, based on the synthesis of three previous models. Hum Reprod 2004; 19 (09) 2019-2026
- 3 van Eekelen R, Scholten I, Tjon-Kon-Fat RI. et al. Natural conception: repeated predictions over time. Hum Reprod 2017; 32 (02) 346-353