Infertility may stem from conditions such as polycystic ovarian syndrome (PCOS), uterine abnormalities, or sperm and egg quality issues. These conditions can be diagnosed and addressed to support fertility. Sometimes standard blood work and fertility tests come back normal, resulting in unexplained infertility. Here are a few things to know about infertility that has no explanation, and what it could mean for patients:
Understanding Infertility
Routine tests may not explain infertility because the standard evaluation doesn’t reveal hidden causes. Fertility doctors perform blood work to check hormone levels and semen analysis to check the quality of the sperm. They use hysterosalpingography (HSG) to check if the fallopian tubes are open. Other assessments include ovarian reserve tests and imaging through ultrasounds and X-rays. If these tests come back normal, it implies that the reproductive system is healthy and should support a pregnancy.
Fertility specialists may recommend trying to conceive naturally for up to a year. If pregnancy doesn’t occur, despite reproductive health seeming normal, patients are often diagnosed with unexplained infertility. This diagnosis is based on exclusion, meaning the doctor is unable to identify the cause through standard evaluations. Other causes of infertility, which are not detectable on these tests, may then be explored. These can include poor egg quality or maturation, endometriosis, and issues with uterine receptivity or embryo implantation.
Diagnosing Possible Causes
When standard tests don’t reveal a cause for infertility, doctors may recommend other assessments to check for hidden issues. A BCL6 test helps check for markers of endometriosis, which is among the leading causes of infertility. Endometriosis occurs when endometrial tissues grow outside the uterus. Normal endometrial tissues grow in the uterus in anticipation of fertilization and implantation. When fertilization doesn’t occur, the tissues are shed during menses. Endometrial tissue growth and shedding are regulated by estrogen and progesterone.
In endometriosis, these tissues grow in the pelvic cavity, around the ovaries, or inside the fallopian tubes. They can block pathways for sperm or affect uterine conditions, resulting in infertility. Although some cases cause pelvic pain and other symptoms, endometriosis sometimes remains silent for years. A positive BCL6 test usually warrants further evaluation through biopsies and imaging to confirm an endometriosis diagnosis. Fertility doctors can also recommend other assessments, such as:
- CD138: Tests for markers of chronic bacterial infections, such as endometritis
- Progesterone receptor testing: Checks how well your uterine lining responds to progesterone to determine resistance
- Immunologic testing: Helps identify immune system imbalances and anti-sperm or anti-embryo antibodies that interfere with conception
If your infertility can’t be explained after standard evaluations, hidden issues like endometriosis, endometritis, and progesterone resistance are likely causes. Fertility doctors usually review all possible causes using specific tests, such as BCL6 and subsequent laparoscopy for endometriosis confirmation. They can also check for sperm DNA fragmentation, immunological factors that affect sperm or embryo function, and issues with cervical mucus.
Addressing Infertility
Following a comprehensive evaluation, fertility specialists may have a possible explanation for infertility. They address each issue identified, then recommend natural conception or assisted reproductive technologies (ARTs) depending on their severity. If the underlying issue is endometriosis, doctors may recommend hormonal therapy, surgical removal, and ARTs like in vitro fertilization (IVF). For endometritis and other chronic infections, fertility doctors often prescribe antibiotics designed to target the identified bacteria.
Progesterone resistance and hormone imbalances may be addressed by introducing synthetic versions of hormones to increase receptivity. Fertility doctors may also recommend optimizing your health through a balanced diet, regular sleep, and regular exercise. If natural conception is not possible, IVF, intrauterine insemination (IUI), or other ARTs can help patients become pregnant. Doctors customize the evaluation and treatment, and may offer additional suggestions, such as weight management, intercourse timing, or donor sperm and egg.
Treatment plans are often adjusted as patients’ needs evolve. Ongoing monitoring, follow-up testing, and open communication with care teams support an effective path forward. With personalized strategies, many patients achieve improved diagnostic clarity and better treatment responses.
Explore Your Next Steps After Unexplained Infertility
Infertility can be managed, even if initial evaluations do not pinpoint the underlying cause. Additional tests focus on hidden causes, such as endometritis, endometriosis, and progesterone resistance. Working with a fertility specialist can help you move forward with personalized care and increased chances of achieving a healthy pregnancy. Get tested today to identify possible reasons for unexplained infertility.
