Uterine Fibroids and Recurrent Pregnancy Loss

Lab value


Female parent karyotype


Male parent karyotype



8 ng/mL


1.5 μU/mL



Lupus anticoagulant

Not detected

Anti-beta-2-glycoprotein 1

Not detected

Anti-cardiolipin IgG

Not detected

As per ASRM guidelines (2012), suggested investigations for RPL assess potential contributing factors related to genetics, antiphospholipid syndrome (APS) , anatomic uterine anomalies, and hormonal and metabolic factors.

Parental karyotyping is recommended to detect any balanced translocations that are present in an estimated 2–5% of cases of recurrent pregnancy loss.

As well, APS should be ruled out by testing for lupus anticoagulant, anti-beta-2-glycoprotein, and anticardiolipin IgG/IgM. 5–20% of women with recurrent pregnancy loss will test positive for APS antibodies. As per the International Consensus Classification criteria for the antiphospholipid syndrome APS is present if one of the following clinical and laboratory criteria are met [15].

  1. 1.

    Clinical Criteria:

    1. (a)

      Vascular thrombus


    2. (b)

      Pregnancy morbidity

      • One or more unexplained losses of morphologically normal fetus >10 weeks’ gestational age

      • One or more unexplained losses of morphologically normal fetus before 34 weeks’ gestational age due to severe preeclampsia or eclampsia as per standard definitions or placental insufficiency

      • Three or more consecutive unexplained losses of morphologically normal fetuses <10 weeks’ gestational age



  2. 2.

    Laboratory Criteria:

    1. (a)

      Lupus anticoagulant in plasma on two or more occasions at least 12 weeks apart


    2. (b)

      Anticardiolipin IgG and/or IgM in serum or plasma present in medium or high titer (>40 GPL or MPL or greater than the 99th percentile) on two or more occasions at least 12 weeks apart


    3. (c)

      Anti-beta-2-glycoprotein-1 IgG and/or IgM on 2 or more occasions at least 12 weeks apart



Maternal endocrine disorders should also be ruled out. If TSH levels are within normal range (i.e., <2.5 μU/mL) there is no indication to check thyroxine (T4) levels or antithyroid antibodies [16]. Uncontrolled diabetes is also a risk factor; therefore HgA1C or fasting glucose should also be included in initial investigation for RPL [17]. Prolactin is also measured because hyperprolactinemia affects the hypothalamic-pituitary axis and may cause RPL.


The patient’s incidental diagnosis of the intramural mass was made during her dating ultrasound at 7 weeks’ gestational age. Appearance was most consistent with an intramural fibroid and it was estimated to be 10 cm in diameter (Fig. 17.1).


Figure 17.1
(a) Sagittal view of intramural fibroid on detailed ultrasound estimated to be 11.9 cm × 12.1 cm × 8.86 cm on transabdominal ultrasound. (b) Hysterosalpingogram confirming patency of fallopian tubes bilaterally and normal uterine cavity contour with no lesions detected. (c) Transabdominal ultrasound showing large intramural fibroid and fetal head. (d) Transabdominal ultrasound showing large intramural fibroid

Transvaginal ultrasound has been shown to be accurate, efficient, safe, and cost-effective method of detecting the presence of fibroids (sensitivity: 99%; specificity: 91%) [18]. However, this level of accuracy is dependent on uterine volumes <375 cm3 and when the number of fibroids is between 1 and 4.

There has been substantial research of the use of magnetic resonance imaging (MRI) in the evaluation of fibroids. In the double-blind study by Dueholm et al. [19] the accuracy of detecting the presence of fibroids was comparable to transvaginal ultrasound with sensitivity of 99% and specificity of 86% with pathological examination the gold standard. However, MRI is superior to transvaginal ultrasound when uterine volumes are greater than 375 cm3 and the number of fibroids exceeds 4. MRI is also superior in determining location and correct uterine wall embedment (i.e., intramural component). Of course, the drawbacks of MRI for evaluation of intramural fibroid are accessibility and cost. However, MRI should be obtained when fibroid mapping is critical, for example when planning an advanced surgical procedure.

Saline infusion sonography (SIS) uses saline injected into the uterine cavity as contrast to enable improved definition of submucosal fibroids, endometrial polyps, endometrial hyperplasia, or carcinomas. SIS is noted to have 83% sensitivity and 90% specificity for submucosal fibroid detection; however it is not considered to be as efficient at assessing intramural fibroids [19].

Hysterosalpingogram (HSG) is classically useful in evaluating patency of the fallopian tubes, excluding intrauterine pathology, and evaluates the contour of the endometrial cavity. However, this imaging modality has a sensitivity of 50% and positive predictive value of 28.6% for intrauterine lesions such as polyps and submucosal fibroids [20]. It is not considered a useful technique for assessing the myometrium or detecting intramural fibroids.

Treatment Options

Currently there is no medical management of fibroids available that is considered curative. It is generally agreeable that submucous fibroids and intramural fibroids distorting the endometrial cavity should be removed particularly in the context of reproductive complications. In the context of a large intramural fibroid and desire to conceive the patient has two options including expectant vs. surgical management.

In our practice, patients with large fibroids are advised to pursue surgical management, typically a preconception myomectomy. The decision to follow a laparoscopic versus open approach depends on the number and diameter of the fibroids. The criteria used when recommending a laparoscopic myomectomy is as follows:

  1. 1.

    One fibroid <15 cm in diameter


  2. 2.

    Two fibroids <7.5 cm in diameter


  3. 3.

    Three fibroids <5 cm in diameter


If the previously mentioned criteria are not met, then an open approach is advised. For noncavity-distorting intramural fibroids, less than 5 cm surgical management is not advised unless there is distortion of the endometrial cavity or the patient is symptomatic.

For this patient, although she is asymptomatic, because the fibroid is 12 cm in diameter preconception surgical management is recommended. As she has a single fibroid less than 15 cm in diameter she is eligible for a laparoscopic approach. We typically advise the patients to postpone conception for 3–6 months postoperatively to allow for healing of the myoma bed.

The patient had a laparoscopic myomectomy . For detailed techniques of laparoscopic myomectomy, please refer to Chaps. 4, 8, 13, 14, and 16. The patient’s postoperative course was unremarkable. She conceived spontaneously 12 months later. She then delivered a live newborn female via elective caesarean section at 39 weeks’ GA.

Medical Management

Medical management of fibroids is based on the role that estrogen and progesterone may play in regard to growth. Currently, there is no pharmacological treatment available that is considered curative. Contemporary medical treatment is considered an option for symptom control. Available medical therapy is associated with ovulation suppression, reduction of estrogen, and inhibition of estrogen and progesterone at the level of receptors. Theoretically it has the potential to inhibit ovulation, endometrium development, and implantation and should not be used in women wishing to conceive or who are pregnant.

Ulipristal is a relatively new medication, which is a selective progesterone receptor modulator that suppresses neovascularization and cell proliferation while inducing apoptosis of fibroids [21]. Ulipristal’s ability to reduce fibroid volume and symptoms has been well established in clinical trials [2224]; however its effect on fertility and pregnancy outcomes is not known. Case studies and series have reported successful term pregnancies in the context of ulipristal use with surgical resection [2527]. Recently, a case report was published reporting a term pregnancy following ulipristal use without surgery [28]. These studies suggest the potential utility of ulipristal for the reduction of fibroid size in women wishing to conceive but avoid surgical intervention.

However, now there is no recommended medical management for fibroids in the context of women who are planning to conceive or pregnant.


Myomectomy for intramural fibroids may be completed via laparoscopy or laparotomy depending on surgeon preference. Hysteroscopic myomectomy is reserved for fibroids with a submucosal component.

Several, noncontrolled studies suggest a decrease in miscarriage rate after myomectomy. Saravelos et al. found that women undergoing myomectomy demonstrated a decrease in miscarriage rates from 21.7 to 0% and live birth rate increased from 23.3 to 52.0% (p < 0.05), however, only when the fibroid distorted the cavity. Women with fibroids that did not distort the cavity achieved live birth rates of 70.4% without intervention [29].

Another study demonstrated marked reduction in miscarriage rates following laparoscopic myomectomy from 43 to 24%. Fifty-one percent of these fibroids were partially intramural and 28% completely intramural [30].

However, a Cochrane review by Metwally et al. included one RCT that investigated the effects of myomectomy on obstetrical outcomes. This review demonstrated that myomectomy of intramural fibroids had no significant effect on clinical pregnancy rates or miscarriages. In those women that underwent myomectomy (via laparotomy or laparoscopy), this did not result in significant difference for live birth rate, clinical pregnancy rate, miscarriage rate, caesarean section, or preterm delivery [31].

To date, there have been no studies examining the effect of myomectomy on RPL.

Clearly, there is disagreement in the literature that brings up the issue if asymptomatic intramural fibroids should be treated. Myomectomy has unique risks besides the general surgical complications of bleeding, infection, damage to viscous, and postoperative thrombus that also need to be considered when recommending surgical management.

Postoperative adhesions have been noted following myomectomy, with an incidence of 94% when the incision is made on the posterior uterine wall and 55% when anterior [32]. The rate of uterine rupture in pregnancy is 0.002%. Even though the incidence is lower than the risk following previous caesarean section (0.1%), delivery via caesarean section is recommended following transmural incision for abdominal or laparoscopic myomectomy [33].

Two randomized controlled trials (RCTs) have been published comparing outcomes of laparoscopic vs. abdominal myomectomy [34, 35]. Besides time to first live birth (14 vs. 15 months, p = 0.003) and time to first pregnancy (5 vs. 6 months, p = 0.008) there were no other significant differences in reproductive outcomes.

In the literature, myomectomy during pregnancy has not been recommended because of presumed increased risk of bleeding. However, case series have been published with positive outcomes associated with myomectomy performed during pregnancy or C-section [3639].

Uterine Artery Embolization

Uterine artery embolization (UAE) was first introduced in 1995 as a noninvasive technique for treating uterine fibroids [40]. Current contraindications to UAE include pregnancy or desire for future pregnancy.

An RCT published by Mara et al. includes 121 patients with intramural fibroids >4 cm and plans for future pregnancy. Patients were randomized to UAE or abdominal (open or laparoscopic based on surgeon preference) myomectomy [41]. Fifty percent of the UAE group vs. 78% of the myomectomy group conceived. Relative risk of UAE patients for spontaneous miscarriage was 2.79 in comparison to myomectomy.

Another finding in the aforementioned RCT is the significantly elevated FSH levels >10 IU/L 6 months following UAE compared to myomectomy (13.8% vs. 3.2%, p < 0.05). Various other studies have also noted loss of ovarian reserve and increase in ovarian failure in women undergoing UAE.

As well, the incidences of caesarean section and postpartum hemorrhage were also noted to be elevated following UAE (66% vs. 48.5% and 13.9% vs. 2.5%, respectively) compared to control pregnancies [42].

There is also concern about the formation of uterine synechiae following UAE secondary to small particles. Small particles from the embolic material used can enter endometrial arteries causing ischemia, synechiae, or ovarian failure if they pass into the utero-ovarian anastomoses [43].

There are lower pregnancy rates, higher spontaneous miscarriage rates, and greater obstetrical complications such as PPH in women who have had uterine fibroids treated with UAE. At this time, this method of treatment is not recommended in patients with large intramural fibroids who wish to conceive in the future.

Magnetic Resonance-Guided Focused Ultrasound Surgery

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a noninvasive, thermal ablation technique approved by the US Food and Drug Administration (FDA) in 2004. This technique uses MRI to direct ultrasound energy to a focal point within the fibroid which causes tissue necrosis of the tumor with limited damage to surrounding structures. The platform used in the United States, Canada, Europe, Asia, and Australia is the ExAblate 2000 (InSightec), ExAblate 2100 (InSightec), and Sonalleve MR-HIFU (Philips Medical System). One treatment lasts up to 3 h and recovery time is 24–48 h.

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Feb 26, 2018 | Posted by in GYNECOLOGY | Comments Off on Uterine Fibroids and Recurrent Pregnancy Loss

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