Thin Endometrium in Infertility

Dr. Shalini Chawla Khanna

Senior IVF Consultant

• Mrx X,32 years –P1A1L1
• 1st –NVD -7 years Back
• 2nd-Medical Abortion 5 years back followed by D&C for retained products  
• Trying to conceive for 4 years.
• USG shows an 18 mm follicle on Day 13, Endometrial thickness -5 mm, with irregular margins
• History of scanty flow during periods last 3 years.
• HAnalysis –Normal 
• SG –B/L Fallopian Tubes Patent
• Semen

Asherman’s syndrome (AS)

• Intrauterine Adhesions(IUA ) -The presence of adhesions inside the uterine cavity and/or endocervix
• Asherman’s Syndrome –IUA +Symptoms (amenorrhea, hypomenorrhea, recurrent pregnancy loss, infertility, and history of abnormal placentation.
• Prevalence of AS in women with impaired fertility -2.8% to 45.5%.

Risk Factors

• >90% of cases with AS occur after pregnancy-related curettage as the basal layer is destroyed.

Incidence of IUA

• After one curettage -10%
• With at least two curettages -30.6%.

How is it Diagnosed?

Diagnosis 

Transvaginal ultrasound-

• Thin Endometrium with irregular Margins
• Echo dense pattern
• Endometrium interrupted by one or more translucent “cyst-like” areas
• Unenhanced transvaginal ultrasonography alone - sensitivity and positive predictive value as low as 0%.

Hysterosalpingography (HSG)

Hysterosalpingography (HSG)-

• Filling defects are described as homogeneous opacity surrounded by sharp edges.
• Simultaneous evaluation of Fallopian Tubes.
• High false positive rate

• Saline infusion during the ultrasound scan (sonohysterography or SHG)  
• Improves accuracy  - 50.3% in the HSG group and 81.8% in the SHG group).
• 3D ultrasound and intrauterine saline infusion (Three-dimensional sonohysterography,3D-SHG)
• Sensitivity and Specificity -91.1% and 98.8%.

MRI

• Especially when  totally obliterated uterine cavity  
• IUA is visualized as low signal intensity on T2-weighed images inside the uterus [32].
• Expensive
• Hysteroscopy remains the gold standard in the assessment of AS.

Management and treatment of Asherman’s syndrome

The treatment strategy for AS  4  main steps:

1. Treatment (Dilatation and curettage, hysteroscopy)
2. Re-adhesion prevention (Intrauterine device, Uterine balloon stent, Foley’s catheter, Anti-adhesion Barriers)
3. Restoring normal endometrium (Hormonal treatment, stem cells)
4. Post-operative assessment (Repeat surgery; diagnostic hysteroscopy; ultrasound).

Hysteroscopic surgery – Principles

• Flimsy Lesions -Tip of the hysteroscope and uterine distension  enough to break down the adhesions -” no touch technique’
• Removal of the adhesions should start from the lower part of the uterus and progress toward the upper part.
• Any central and filmy adhesions separated initially in order to allow adequate distension of the uterine cavity.
• Dense and lateral adhesions should be treated at the end - the greater risk of uterine perforation and bleeding.

Hysteroscopic Surgery – Principles

Cold-knife approach> Electric Surgery

• Potential damage to the residual endometrium.
• Bipolar superior to Monopolar  -tissue effect is more focal, use of electrolyte-containing uterine distension media - that electrolyte changes are less likely to be clinically serious in cases of fluid overload.
• Laser - Nd-YAG (neodymium-doped yttrium aluminum garnet) and KTP(potassium-titanyl-phosphate)
• Higher costs and increased uterine damages

Prevention of adhesion recurrence

The rate of IUA reformation after surgery remains high (3.1% to 23.5%). These adhesions usually tend to be thin and filmy

IUD

• Helps in  Physiological Endometrial Regeneration by separating the anterior and posterior uterine walls.
• Nevertheless, some authors believe that inflammatory factors released by copper devices could aggravate the endometrial injury
• IUD is retained for 2-3 months
• No difference in adhesion reformation among women randomized to receive an IUD device, estrogens treatment, or no treatment after hysteroscopic septum resection Touguc et al.
• The Levonorgestrel-releasing IUD is Not Recommended.

Foley Catheter

• Higher conception rate compared with the IUD group (33.9% versus 22.5%).
• 81% of women restored their normal menstrual pattern.
• Follys catheter- retained inside the uterus for ten days.
• Complication -Uterine perforation,  Ascending infection from the vagina, and high discomfort.

Intrauterine balloon stent

• Silicon made -Triangular shape device fits the normal triangular shape of the uterine cavity (Cook Medical Inc, Bloomington, USA).
• 1240 patients treated - Pregnancy rate of 61.6% and spontaneous miscarriage rate of 15.6%.
• No data about IUA recurrence was reported.
• A prophylactic broad-spectrum antibiotic is Recommended to prevent infection.
• Although this is encouraging evidence, data about its safety and efficacy seem still insufficient.

Hyaluronic acid

• Hyaluronic acid generates a temporary barrier between organs which mechanically adhesions formation
• In addition, these products influence peritoneal tissue repair by increasing the proliferation rate of mesothelial cells
• Autocross-linked hyaluronic acid (Hyalobarrier)
• It is a highly viscous gel formed by the autocross-linked condensation of hyaluronic acid
• It can prevent intraperitoneal adhesion after laparoscopic myomectomy and intrauterine adhesions after a hysteroscopic procedure
• Chemically modified hyaluronic acid (sodium hyaluronate) and carboxymethylcellulose (Seprafilm).
• Alginate carboxymethylcellulose hyaluronic acid- Four weeks after surgery, intrauterine adhesions were significantly lower compared with carboxymethylcellulose hyaluronic acid (187 patients )

Restoration of normal endometrium

• Medical therapy –Estrogen
• Encourage fast growth of any residual endometrium immediately after surgery with the dual purpose of preventing new scar formation, increasing endometrial thickness, and restoring a normal uterine environment.
• Estrogen Supplementation -No conclusion on the ideal dosage, the timing of Estorgen, or the route of administration (vaginal or oral).
•  4 mg and 10 mg estradiol orally -No superior effect of the high dosage was demonstrated.

Complications of AS

• Obstetric complications may occur-
• Lower birth weight
• Increased incidence of preterm delivery and retained placenta (placenta accreta in 10.7% of the patients

The success of Hysteroscopy A3

• An overall pregnancy rate from 40% to 63% was previously described.

Stem cells and endometrial regeneration

• Regeneration of endometrium through stem cell treatment has been evaluated both in animal models and in small experimental human studies.
• Bone marrow-derived stem cells, mesenchymal stem cells, and autologous menstrual blood-derived stromal cells have been investigated.
• Different application methods have been used -Infusion in spiral arterioles through catheters, trans myometrial administration to the sub-endometrial area, and direct installation of stromal cells in the uterine cavity after endometrial scratching.
• Future randomized trials are needed to prove if stem cell treatment will have a clinical role in AS

Second-look hysteroscopy

• Post-treatment assessment of the uterine cavity is recommended one-two month after the initial surgery.
• 50% and 21.6% of recurrence in severe and moderate AS respectively
• Second-look hysteroscopy with the division of newly formed adherences ( retrospective study, 151 patients), 
• cumulative pregnancy rate (77% vs 56%), and live birth rate (77% vs 63%)

Resistant Thin Endometrium

• Drugs to increase Endometrial Blood Flow –
• Pentoxifylline 800 mg/day
• Tocopherol 1000 mg/day, several months
• Sildenafil 100 mg/day, vaginal pessary
• L‑arginine 6 g/day,
• Low-dose aspirin 75 mg/day.
• None of these therapies have met with much success.