Unexplained Infertility: Management Goals

unexplained infertility
Unexplained Infertility

When you are struggling to conceive it is the rationale to have a fertility consultation. Usually, infertile couples are advised to seek consultation after one year of trying. In this situation, if your doctor doesn’t find a cause after an initial investigation, she may call it unexplained infertility. Among all infertile couples worldwide in 30% of cases remain undiagnosed. Here there is no obvious cause for infertility. So, the females’ inability to get pregnant after at least 12 cycles of unprotected intercourse for whom all the standard evaluations are normal is called unexplained infertility.

Tests for unexplained infertility

Before calling it unexplained your specialist conducts certain necessary tests. These are semen analysis, assessment of ovulation and the luteal phase, and assessment of tubal patency by hysterosalpingogram or laparoscopy. There are certain other tests that are not included in the basic investigation.  Whether to include those tests or not depends on your clinical evaluation. Your doctor may not be sure about the efficacy or importance of these controversial tests. These tests are endometrial biopsy, ovarian reserve (AMH, AFC), post-coital test and serum prolactin levels. Specialized fertility centers advise extensive advanced tests to find the causes of failed conception. These may include ovarian and testicular dysfunctions, sperm and oocyte quality, fallopian transport defects, endometrial receptivity, implantation failures, and endometriosis.

Are unexplained infertility patients different from the infertile couples with definite causes?

If you fail to conceive without an obvious cause then it is advisable not to panic. You have more chances of conception than those with a cause. That is to say, the rate of spontaneous conception in these couples is more than the couples with defined causes of infertility. To clarify, the rate of spontaneous pregnancy is 13-15% during the first year of attempt which increases to 35% during the next two years of attempt. Moreover, the rate could reach 80% in younger couples during the following three years of unprotected intercourse without any adjuvant therapy. But, the rate of spontaneous pregnancy drastically declines with infertility duration of more than 3 years and in women over 30 years of age.

Why IVF treatment is advised for Unexplained Infertility?

The decision for treatment in unexplained infertility will depend on several factors. If you are more than 35 yrs. or a career-oriented woman, you may wish to complete family early.

On the other hand, the couple’s impatience for completion of standard protocols enforce for advanced treatment like IVF or ICSI. A higher success rate with ART treatment lures the fertility specialist and the infertile couple to take a decision in favour of it.

Compared to other options in infertility clinics lead to the diversity of clinical practice regarding unexplained infertility. Failure in the implementation of standard practice for the treatment of unexplained infertility leads to overtreatment in most of the cases. The first-line treatment would be simple, low-cost and non-invasive. It will be favorable for you to opt for a simpler option and follow the protocol.

Management of unexplained infertility

  • It depends on the age of women and infertility duration. It will be advisable for you to wait for 2 years is if your age is less than 30.
  • Awareness of fertility facts like ovulation period and timing of intercourse is important for conceiving. Before any active medical intervention, it is better you try he natural way for some time.
  • The use of ovulation induction is trivial for women with unexplained infertility. If the long period of expectant management cannot lead to pregnancy, ovulation induction by clomiphene and letrozole is not effective for these couples.
  • Also, insemination cycles without ovarian stimulation will have little benefit for you. Usually, you will require more aggressive induction with injectable hormones.
  • However, hyperstimulation and IUI may not be ineffective for couples with long duration of unexplained infertility.
  • Couples over 35 and couples with long duration of infertility are suitable candidates for IVF
  • Failed fertilization is reported in 8.4%-22.7% of IVF cycles for couples with unexplained infertility

Laparoscopy for Unexplained Infertility

You may have to undergo a laparoscopy before IUI as HSG may nor be accurate in all cases. The potential role of laparoscopy in the complete workup of unexplained infertility will be explained to you before the procedure. Approximately 15% to 30% of couples will be diagnosed with unexplained infertility after their diagnostic workup.

Assessment of Male Infertility

If the semen analysis is abnormal, it should be repeated after at least 1 month by a laboratory that adheres to World Health Organization (WHO) guidelines. The values given by WHO are followed as threshold values for sperm concentration, motility, and morphology. It can be used to classify men as sub fertile or not.

If any abnormalities are repeatedly detected on a semen analysis, referral to a urologist may be warranted. The treatment of severe male factor infertility including azoospermia has been revolutionized with the combination of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

Previously, the postcoital test (PCT) assessing the sperm motility in a sample of postcoital cervical mucus was considered an integral part of the basic infertility evaluation. Today, the PCT has been largely abandoned and not recommended it as a component of the standard infertility workup.

Assessment of Ovulation

Ovulatory defects are commonly present and found in 40% of infertile women. It accounts for approximately 15% of cases of infertility. If you have menstrual abnormalities then you will be investigated for underlying causes such as polycystic ovarian syndrome, thyroid disease, hyperprolactinemia and causes secondary to weight changes.

To evaluate ovulation your basal body temperature (BBT) recordings are important. You can also check with urinary luteinizing hormone (LH) ovulation predictor kits. Kits are also available for mid luteal serum progesterone testing.  Endometrial biopsy to assess for secretory endometrial development may be advised to you.

Serum progesterone levels higher than 3 ng/mL suggest that ovulation has occurred and levels higher than 10 ng/mL are satisfactory.

Assessment of Ovarian Reserve

The testing includes a cycle day 3 serum follicle-stimulating hormone (FSH) and oestradiol level, clomiphene citrate challenge test, and/or an ultrasonographic ovarian antral follicle count. Your serum AMH will guide to the ovarian capacity. This test can be done on any day of the menstrual cycle.

Assessment of Uterus and Fallopian Tubes

This may be achieved by hysterosalpingography (HSG). Along with laparoscopic dye perturbation, it can best assess tubal patency. A complete cavitary assessment, however, necessitates either sono hysterography for conditions such as uterine polyps, submucous leiomyomas, or Asherman’s syndrome (uterine synechiae).

Sonohysterography, an office procedure, involves assessing the uterine cavity with ultrasound with concurrent instillation of sterile water. Some practitioners prefer diagnostic office hysteroscopy as it allows direct visualization of the uterine cavity.

Laparoscopy should be performed in women with unexplained infertility or signs and symptoms of endometriosis or in whom the reversible adhesive tubal disease is suspected

Treatment of Unexplained Infertility

The principal treatments for unexplained infertility include expectant observation with timed intercourse and lifestyle changes, clomiphene citrate and intrauterine insemination (IUI), controlled ovarian hyperstimulation (COH) with IUI, and IVF.

Expectant Management and Lifestyle Changes

Smoking or using excessive caffeine can reduce your chances of conceiving. Similarly, weight gain in excess also has a negative effect on fertility. A healthy diet with moderate exercise helps achieve your goal by normalizing hormone levels. If you are a PCOS woman then you must consult check your sugar levels for abnormalities. The female partner is counseled to achieve a normal BMI, reduce caffeine intake to no more than 250 mg daily (2 cups of coffee), and reduce alcohol intake to no more than 4 standardized drinks per week. The likelihood of pregnancy without treatment among couples with unexplained infertility is less than that of fertile couples. But with lifestyle management, you have a chance to achieve pregnancy.

Laparoscopy as a Treatment

During diagnostic laparoscopy, some women undergo resection or ablation of visible endometriosis. Laparoscopic resection or ablation of minimal and mild endometriosis enhances fecundity in infertile women.

It may improve pregnancy success rates in minimal endometriosis. During laparoscopy your doctor may flush the tubes to open up, it works for some women with flimsy occlusion. At times the surgeon removes adhesions or cysts which may work positively for you.


Many fertility centers perform IUI with natural ovulation. You can use the LH kit for timing of ovulation during induction using clomiphene citrate, or injectable gonadotropins. Intracervical insemination alone doesn’t work effectively and has lower pregnancy rates per couple compared with IUI alone. IUI in unexplained infertility will require better follicular growth. Therefore, IUI without additional treatment with clomiphene citrate or gonadotropins will not yield any benefits to couples with unexplained infertility.

Ovulation induction and IUI

Usually, IUI in unexplained infertility is performed with multiple follicular growths. Both clomiphene citrate and gonadotropins can be used for stimulation. IUI is done by introducing washed sperm into the uterine cavity. It may increase the density of motile sperm available to ovulated oocytes. As a result, the chances of fertilization are maximized. The cumulative pregnancy rate rises with the number of attempted COH/IUI cycles. Hence, your doctor will advise you for consecutive cycles of IUI to attain success.


The most successful treatment of unexplained infertility consists of the spectrum of assisted reproductive technology including IVF, with or without ICSI. IVF is the treatment of choice for unexplained infertility. If you have oocytes with thick covering you will benefit from ICSI. ICSI is an advanced procedure that helps you to achieve fertilization in 90% cases.

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