This patient’s history and physical exam findings are consistent with polycystic ovary syndrome (PCOS ), but other causes of oligomenorrhea and anovulation should also be ruled out. Polycystic ovary syndrome is a well-recognized cause of infertility due to chronic anovulation , and it is not likely that her small fibroids that are asymptomatic are contributing to her infertility at this time. This case represents an example of where the underlying cause of infertility should be recognized as a separate medical issue from her fibroids. The next steps involve the laboratory evaluation of oligomenorrhea and androgen excess, then associated testing for metabolic disorders due to PCOS, followed by the treatments indicated to induce ovulation.

The revised 2003 criteria for PCOS diagnosis include having two out of three of the following: chronic anovulation and/or clinical or biochemical signs of hyper-androgenism and or polycystic ovaries with no evidence of related disorders [1]. This includes ruling out a thyroid disorder with thyroid function studies and prolactin level to rule out hyperprolactinemia. Other laboratory studies that may be indicated, depending on the severity of androgen excess symptoms, might include a 17-hydroxyprogesterone level, DHEA-S, and a total and free testosterone.

Women with PCOS need to be evaluated for metabolic syndrome before starting infertility treatment. Insulin resistance plays a crucial role in PCOS. As part of preconceptual health screening, this patient should be screened for hyperlipidemia, hypertension, and diabetes. A history looking for potential cardiac events and stroke should be obtained. In this patient, a hemoglobin A1c and a lipid panel would also be checked. The hemoglobin A1c will help guide therapy by determining if there is impaired glucose tolerance causing prediabetes or adult-onset type 2 diabetes. If this is found to be the case, metformin could be started in this patient. Lifestyle modification with diet, exercise, and weight loss would also be indicated.

For patients with PCOS, weight loss should be encouraged as this can regulate menstrual cycles and make fertility treatment more effective. Lifestyle modification with diet, exercise, and weight loss would also be indicated if she is overweight or obese.

For the incidental fibroids found in her exam and TVUS, their location (intramural), size (1–2 cm), and normal structure of her uterine cavity would result in a recommendation against a myomectomy. This patient’s fibroids would be monitored throughout her pregnancy to assure that they are not significantly growing in size.

For ovulation induction, letrozole is now the first-line therapy, over clomiphene citrate. Because of the normal semen analysis, intrauterine insemination (IUI) is not the first-line therapy, but a discussion with the patient is vital in determining if they would like this procedure done as well. Other options include clomiphene citrate, gonadotropin therapy, and in vitro fertilization (IVF) to assist in reproduction.

When a workup for infertility is completed, the most common causes for infertility should be considered. Ovulatory dysfunction, as seen in PCOS , makes up about 30% of the causes of female infertility [1]. Tubal factors are a growing cause of infertility due to the increased incidence of chlamydial and gonococcal salpingitis. Male factor as the cause of infertility makes up 20–30% of cases [2]. Peritoneal factor, particularly endometriosis, and advanced maternal age or diminished ovarian reserve should also be considered. In this case, this woman can clinically be diagnosed with PCOS, which is likely the cause of her primary infertility. Incidental fibroids were found on her clinical exam and confirmed by the TVUS.

Uterine fibroids are common benign tumors seen in up to 40% of women. Whether fibroids affect fertility is still a topic of debate and study with no definitive answer available for all types and location of uterine fibroids. Studying the exact effect of fibroids becomes complex due to the variation in size, location, number, and composition, in addition to several confounding factors. Fibroids are classified based on their location in the uterus as submucosal, intramural, and subserosal. Within these, the Federation of Gynecology and Obstetrics (FIGO) subdivided them based on percent within each of these locations [3]. The range is from type 0 where the submucosal fibroid is completely inside the uterine cavity to type 7 where the subserosal fibroid is completely inside the pelvis (Table 12.1).

A meta-analysis of 18 studies by Pritt et al. was performed in 2009 to compile the data on the effects of fibroids on fertility [4]. When comparing women with myomas to control subjects, there was noted to be decreased implantation, ongoing pregnancies, and live birth rates. When fibroids were stratified by location, submucosal fibroids showed decreased clinical pregnancy rates, implantation rates, ongoing pregnancy/live birth rate, and increased spontaneous abortions compared to women without fibroids. There was no increase in preterm delivery in these women. When comparing women with fibroids with no intracavitary involvement to women with no fibroids, the data showed that implantation rates and ongoing pregnancy/live birth rates were lower and spontaneous abortion rates higher overall. Fibroids that did not distort the cavity did not seem to lower fertility. When non-distorting fibroids were split into subserosal and intramural fibroids , subserosal fibroids seemed to have no effect on fertility or pregnancy, while intramural fibroids did have negative effects on fertility and pregnancy. This conclusion is not definitive as many of these studies had poor evaluation of the uterine cavity. Most of the studies used hysterosalpingograms or transvaginal ultrasounds. Hysterosalpingograms can have sensitivities as low as 50% for intramural fibroids [5]. Transvaginal ultrasound has sensitivities a low as 69% when compared to hysteroscopy, which is the gold standard [6]. Currently sonohysterogram, hysteroscopy, and magnetic resonance imaging (MRI) are the best techniques available to diagnose the presence of intracavitary or submucosal fibroids [7]. Many of these studies also did not include the size of the fibroids, location of the intramural fibroid, or the proximity to the endometrium.

In 2010, Sunkara et al. performed another meta-analysis of 19 observational studies on infertility and fibroids. They concluded that subserosal myomas do not affect fertility and submucosal fibroids are detrimental to fertility [8]. They limited the size range of intramural fibroids from 0.7 to 5 cm and those not impinging on the intrauterine cavity. They did find significantly more adverse pregnancy outcomes and a reduced live birth rate in women with intramural non-distorting fibroids but called for well-designed randomized control trials.

It appears that size is an independent variable that determines the fertility and pregnancy outcomes in a woman. Some of the most recent studies show an association between size and pathogenesis, but they do not agree on the cutoff size for intramural fibroids. Recently Yan et al. found that patients with intramural fibroids greater than 3 cm did have lower delivery rates when compared to unaffected women [9]. Somigliana et al. found that intramural fibroids less than 5 cm had similar live birth rates to the control group [10]. Clearly, size may alter fertility and pregnancy outcomes. The size that appears to significantly decrease fertility rates and adversely alter pregnancy outcomes is not well established but appears to be around 3–4 cm.

The question remains: When is it reasonable to perform a myomectomy to improve fertility in the presence of intramural fibroids? If this patient had submucosal fibroids , it would be clear that she needed hysteroscopic myomectomy before undergoing ovulation induction to restore a normal cavity before pregnancy. The studies that have examined this include Bulletti et al. who found that delivery rates were significantly higher in patients with laparoscopic myomectomies (42%) compared to patients with fibroids that did not undergo myomectomy (11%, p < 0.001) [11]. Subsequent work by this group demonstrated that intramural-subserosal fibroids >5 cm that were excised had a pregnancy rate that was 25% higher in those with surgery compared to those without (p < 0.01) [12]. The 2009 meta-analysis on surgical management of fibroids found that surgical excision of submucosal fibroids improved fertility, but the data supporting this was limited, and they did not find it beneficial to excise intramural fibroids [4]. Gilliano et al. also found that mixed submucosal intramural fibroids can disrupt the endometrial cavity and result in poor results from IVF [13]. Whether removing intramural fibroids will normalize fertilization is not known, and there are many reasons to avoid unnecessary myomectomies. Abdominal and laparoscopic myomectomy have associated risks, including the risk of damage to internal organs, infection, blood loss, postoperative adhesions, and greater risk of a cesarean section and uterine rupture in pregnancy. Given the limited trials and significant risks associated with abdominal or laparoscopic myomectomies, at this time, it is not recommended to perform myomectomy for small intramural fibroids. This is especially true for fibroids less than 4 cm [9].