Medical management of adenomyosis: current and future therapies

The current issue of Journal of Fertility and Sterility has focused exclusively on etiology, pathophysiology, and medical and surgical treatment of adenomyosis. Adenomyosis has long been the source of controversy and its only with the recent advent of Transvaginal sonography (TVS) and MRI that its etiology and pathophysiology been better understood.

Adenomyosis is a uterine pathology in which the endometrial glands and stroma invaginate within the uterine myometrium. This ectopic endometrium induces hypertrophy and hyperplasia of the myometrium resulting in the typical ‘globular” enlargement of the uterus.

It is also now known that endometriosis and adenomyosis are two different phenotypes of the disorder characterized by impaired cellular response to ovarian hormone. This concept has to lead to the use of common treatment modalities for both the diseases.

Transvaginal sonography (TVS) and MRI are now the gold standards for diagnosing adenomyosis. Adenomyosis requires a lifelong treatment plan that depends upon patient’s age, desire for children and symptoms. Medical management is the treatment of choice for women who want to preserve fertility, while hysterectomy is preferable in older women who have completed the childbearing.

No new drug has been developed in recent years for the treatment of adenomyosis although many new drugs are under development and undergoing clinical trials.  

Medical management includes minimally invasive procedures as well as medication to treat the symptoms.

Minimally invasive surgical procedures help preserve fertility as well as reduce the pain and abnormal uterine bleeding (AUB) and include endometrial ablation and resection, laparoscopic as well as open excision of adenomyosis and MRI-guided focused ultrasound. They are offered to patients who have not responded to medical drug treatments. 

The medical treatment is mainly aimed at easing the symptoms, improving quality of life and promote fertility. The rationale behind using these drugs is based on the pathophysiology of the disease which includes aberrant response to the ovarian hormone, inflammation, and impaired apoptosis.

http://journals.sagepub.com/doi/full/10.5301/je.5000261

The class of drugs includes:

Current Medical Treatments: 

GnRH agonist: These group of drugs cause a downregulation of GnRH activity and induce a reversible state of medical menopause. Goserelin, leuprolide, and nafarelin are commonly used in clinical practice before fertility treatments to improve the chances of pregnancy in infertile women with adenomyosis.

Progestins: Drugs such as danazol, norethindrone acetate (NETA), Levonorgestrel-releasing intrauterine system (LNG-IUS), and Dienogest are mainly used because of anti-inflammatory properties to relieve pain and reduce the amount of abnormal uterine bleeding.

The Levonorgestrel-releasing intrauterine system (LNG-IUS) has been found extremely effective in reducing menorrhagia and decrease the uterine volume over a period of 12 months use.

Combined oral contraceptives (COC): They are effectively used to reduce pain and control bleeding with the additional advantage of long-term use with minimal side effects.

Future Medical treatments:

Selective estrogen receptor modulators (SERMs)

Aromatase inhibitors (AIs)

Selective progesterone receptor modulators (SPRMs)

Valproic acid

Anti-platelets therapy

NSAIDs

Thus, the medical treatment of adenomyosis comprises many current and future drugs. No double-blind, RCTs have yet been conducted in the management of adenomyosis and the drugs are solely used based on results of observational studies.

Abstract

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ACOG updates its guidance on Neural Tube Defects

ACOG has recently released its updated guidance on Neural Tube Defects (NTDs) and includes guidelines about prevention, screening, antenatal management and delivery in pregnancies with  such defects. The practice bulletin No.187 is published in December issue of Journal Obstetrics and Gynecology.

NTDs is the second most common group of congenital malformation after cardiac anomalies. The prevalence differs according to race, region and environmental influences.

In contrast to other malformations, NTDs are preventable by supplementation of folic acid.  

The recommendations:

ACOG along with other professional organizations like CDC, AAFP, AAP, ACMG and AAN: Women in the reproductive age group, having the capacity to become pregnant should take at least 0.4 mg (400 µg) of folic acid daily.

USPSTF: all women who are planning or capable of pregnancy take a daily supplement containing 0.4 to 0.8 mg (400-800 µg) of folic acid.

ACOG, CDC other organization suggests a higher dose of 4 mg (4000 μg) of folic acid for women who are at high risk of having a baby with NTD. These factors are:

Previous history of pregnancy with NTD

Having a partner with NTDs or a partner who previously has had a child with NTD

Patients with a second or third degree relative with NTD

Patient herself was born with NTD

History of taking anti-epileptic medication Valproic acid

Type 1 Diabetes Mellitus

Obesity.

ACOG has also made additional recommendations in the recent 2017 updates.

With Advancements in Ultrasound techniques, Maternal Serum Alpha Feto Protein (MSAFP) has become less important in diagnosing NTDs, when high quality, second trimester ultrasound is routinely used.

MSAFP is more important for screening for other anomalies and placental complications in such cases.

If MSAFP value is ≥ 2.5 MoMs, the detection rate for anencephaly is 95% and 65-80% for other open NTDs.

2D ultrasound has a detection rate of 96% and if structural abnormalities are seen on Ultrasound, they can be considered diagnostic.

3D ultrasound is not superior to 2D in diagnosing NTDs; however, it may be more helpful in delineating the upper limit of spinal defects.

The rates of diagnosing NTDs in first trimester are lower than that of 2^nd trimester sonography.

MRI is not mandatory if NTD has already been identified in sonography.

Pregnancy and delivery management:

After a pregnancy with NTD is diagnosed options should be individualized according to each pregnancy:

Pregnancy termination

In Utero fetal surgery for repair

Expectant management with neonatal surgical repair.

Studies on In-Utero repairs have demonstrated that such neonates have functional level two or more times better than expected, and reduce the neonatal mortality and morbidity.

Delivery:

Regarding the timing of delivery, term delivery is preferred. Elective late preterm or early term cesarean is only considered if fetal repair has been done or other obstetric indication for surgery exists.

Retrospective studies with not very long-term follow-up have demonstrated no increased risk of vaginal delivery, but each case needs to be individualized.

Practice Bulletin Abstract

USPSTF recommendations

CDC recommendations

ACOG committee opinion on Fetal Myelomeningocele Repair

ACMG policy statements

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Media: Univision.com