Unexplained infertility is infertility that is

idiopathic An idiopathic disease is any disease with an unknown cause or mechanism of apparent spontaneous origin. From Greek ἴδιος ''idios'' "one's own" and πάθος ''pathos'' "suffering", ''idiopathy'' means approximately "a disease of its own kin ...

in the sense that its cause remains unknown even after an infertility work-up, usually including

semen analysis A semen analysis (plural: semen analyses), also called seminogram or spermiogram, evaluates certain characteristics of a male's semen and the sperm contained therein. It is done to help evaluate male fertility, whether for those seeking pregnanc ...

in the man and assessment of ovulation and fallopian tubes in the woman.merckmanuals > Unexplained Infertility
Last full review/revision November 2008 by Robert W. Rebar, MD It is usually an exercise in excluding all possible causes before making a diagnosis, however the age of the female partner as well as the duration of infertility are often the most scrutinized characteristics of any infertility case.

Possible causes

In unexplained infertility abnormalities are likely to be present but not detected by current methods. Possible problems could be that the egg is not released at the optimum time for fertilization, that it may not enter the fallopian tube, sperm may not be able to reach the egg, fertilization may fail to occur, transport of the zygote may be disturbed, or implantation fails. It is increasingly recognized that egg quality is of critical importance and women of advanced maternal age have eggs of reduced capacity for normal and successful fertilization. Also, polymorphisms in

folate pathway Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...

genes could be one reason for fertility complications in some women with unexplained infertility. Aberrant reproductive immunology such as decreased

maternal immune tolerance Immune tolerance in pregnancy or maternal immune tolerance is the immune tolerance shown towards the fetus and placenta during pregnancy. This tolerance counters the immune response that would normally result in the rejection of something foreign i ...

towards the embryo may also be a possible explanation. However, a growing body of evidence suggests that epigenetic modifications in sperm may be partially responsible.

Prevalence

Globally, about 10% of infertile couples have unexplained infertility.

Management

Potential methods in unexplained infertility include oral ovarian stimulation agents (such as clomifene citrate,

anastrozole Anastrozole, sold under the brand name Arimidex among others, is a medication used in addition to other treatments for breast cancer. Specifically it is used for hormone receptor-positive breast cancer. It has also been used to prevent breast ca ...

letrozole Letrozole, sold under the brand name Femara among others, is an aromatase inhibitor medication that is used in the treatment of breast cancer. It was patented in 1986 and approved for medical use in 1996. In 2020, it was the 257th most common ...

) as well as

intrauterine insemination Artificial insemination is the deliberate introduction of sperm into a female's cervix or uterine cavity for the purpose of achieving a pregnancy through in vivo fertilization by means other than sexual intercourse. It is a fertility treatm ...

(IUI),

intracervical insemination Artificial insemination is the deliberate introduction of sperm into a female's cervix or uterine cavity for the purpose of achieving a pregnancy through in vivo fertilization by means other than sexual intercourse. It is a fertility treatm ...

(ICI) and

in vitro fertilization In vitro fertilisation (IVF) is a process of fertilisation where an egg is combined with sperm in vitro ("in glass"). The process involves monitoring and stimulating an individual's ovulatory process, removing an ovum or ova (egg or eggs) f ...

(IVF). In women who have not had previous treatment, ovarian stimulation combined with IUI achieves approximately the same

live birth rate Pregnancy rate is the success rate for getting pregnant. It is the percentage of all attempts that leads to pregnancy, with attempts generally referring to menstrual cycles where insemination or any artificial equivalent is used, which may be simpl ...

as IVF. On the other hand, in women who have had previous unsuccessful treatment, IVF achieves a live birth rate approximately 2–3 times greater than ovarian stimulation combined with IUI. IUI and ICI has higher

pregnancy rate Pregnancy rate is the success rate for getting pregnancy, pregnant. It is the percentage of all attempts that leads to pregnancy, with attempts generally referring to menstrual cycles where insemination or any artificial equivalent is used, which ma ...

s when combined with ovarian stimulation in couples with unexplained infertility, for IUI being 13% unstimulated and 15% stimulated, and for ICI being 8% unstimulated and 15% stimulated. However, the rate of

twin birth Twins are two offspring produced by the same pregnancy.MedicineNet > Definition of TwinLast Editorial Review: 19 June 2000 Twins can be either ''monozygotic'' ('identical'), meaning that they develop from one zygote, which splits and forms two e ...

increases substantially with IUI or ICI combined with ovarian stimulation, for IUI being 6% unstimulated and 23% stimulated, and for ICI being 6% unstimulated and 23% stimulated. According to NICE guidelines, oral ovarian stimulation agents should not be given to women with unexplained infertility.Fertility: assessment and treatment for people with fertility problems
NICE clinical guideline CG156 - Issued: February 2013 Rather, it is recommended that in vitro fertilization should be offered to women with unexplained infertility when they have not conceived after two years of regular unprotected sexual intercourse. IVF avails for embryo transfer of the appropriate number of embryos to give good chances of pregnancy with minimal risk of multiple birth. A review of randomized studies came to the result that IVF in couples with a high chance of natural conception, as compared to IUI/ICI with or without ovarian stimulation, was ''more'' effective in three studies and ''less'' effective in two studies. There is no evidence for an increased risk of

ovarian hyperstimulation syndrome Ovarian hyperstimulation syndrome (OHSS) is a medical condition that can occur in some women who take fertility medication to stimulate egg growth, and in other women in very rare cases. Most cases are mild, but rarely the condition is severe and c ...

(OHSS) with IVF when compared with ovarian stimulation combined with IUI.

Prognosis

Prognosis in unexplained infertility depends on many factors, but can roughly be estimated by e.g. the Hunault model, which takes into account female age, duration of infertility/subfertility, infertility/subfertility being primary or secondary, percentage of motile sperm and being referred by a general practitioner or gynecologist.

References

{{reflist Infertility

Possible causes

Prevalence

Management

Prognosis

See also

References