Case Report: Endometrios Causing IVF Failures due to Embryo Implantation Dysfunction (IID)

After 4 years of trying to conceive without any success, Rosa (35y) and her husband Jim (42y), achieved a spontaneous pregnancy in 2014. Sadly, the pregnancy miscarried at 5 weeks. Jim had perfectly normal sperm parameters. Rosa underwent a hysterosalpingogram as well as a saline ultrasound hysterosonogram), in 2016. Both were normal.

Then in 2016, Rosa underwent a laparoscopy where she was diagnosed as having moderately severe endometriosis. All visible endometriotic lesions were ablated at that time. She has excellent ovarian reserve (basal FSH= 7.1MIU/ml; AMH=4.2 ng/ml).

Rosa underwent three failed attempts at clomiphene-intrauterine insemination (IUI) in 2016. In July of 2017 she underwent IVF and went on to produce 20 follicles, 16 mature (MII) eggs. All were fertilized successfully by intracytoplasmic sperm injection-(ICSI) and developed into 7 excellent quality blastocysts. Two (2) of these were transferred fresh to her uterus and she conceived but sadly, again  lost the pregnancy very early on.  This left Rosa and with 5 advanced blastocysts frozen and banked.

In March 2018 the couple contacted me for advice on how to proceed. I told them that women with endometriosis (regardless of its severity) have about a 1:2 chance of having an immunologic implantation dysfunction, secondary to increased uterine natural killer cell activity (Nka) and that this is often accompanied by increased levels of blood antiphospholipid antibodies (APA).

Rosa’s blood was tested for Nka and APA at Reprosource Immunology laboratory in Boston, MA. She tested positive for both and in February of 2019 I transferred 2 of her banked embryos transferred in a frozen embryo transfer (FET) cycle. During this cycle she was treated with an infusion of intralipid (IL) and daily oral dexamethasone) to address her Nka+ (initiated +/- 2 weeks prior to embryo transfer) along with daily Lovenox (heparinoid) injections.  She conceived with twins and according to her Obsterician.  Mother and babies are at present  faring very well.

The immunologic implantation dysfunction (IID) are primarily due to Nka+, and compounded by the presence of APA.  NKa cells attack the invading trophoblast cells (developing “root system” of the embryo/early conceptus) as soon as it tries to gain attachment to the uterine wall. In most cases, this results in rejection of the embryo even before the pregnancy is diagnosed and sometimes, in a chemical pregnancy or an early miscarriage. As such, many women with endometriosis, rather than being infertile in the strict sense of the word, often actually experience repeated undetected “mini-miscarriages”.

Women who in addition to Nka+, also harbor APA’s often experience improved IVF birth rates when, in conjunction with IL and steroid therapy,  heparinoids (e.g. Clexane/Lovenox) are administered from the onset of ovarian stimulation with gonadotropins until the 10th week of pregnancy. Intralipid (IL) is a solution of small lipid droplets suspended in water. When administered intravenously, IL provides essential fatty acids, linoleic acid (LA), an omega-6 fatty acid, alpha-linolenic acid (ALA), an omega-3 fatty acid.IL is made up of 20% soybean oil/fatty acids (comprising linoleic acid, oleic acid, palmitic acid, linolenic acid and stearic acid) , 1.2% egg yolk phospholipids (1.2%), glycerin (2.25%)  and water (76.5%).IL exerts a modulating effect on certain immune cellular mechanisms largely by down-regulating NKa. The anti-implantation effect of APA is negated through the administration of heparinoid.

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