Effect of Intralipid Infusion in Patients With Recurrent Implantation Failure

1. Age 20-38 years of age.

2. Recurrent implantation failure, defined as failure to achieve a recognizable intrauterine gestational sac by ultrasonography after transfer of at least four good-quality embryos in a minimum of three fresh or frozen IVF cycles (Coughlan et al, 2014).

   Good-quality embryos will be defined as those characterized by absence of multinucleated blastomeres, four or five blastomeres on day 2, seven or more cells on day 3, and ≤ 20% anucleated fragments (Van Royen et al, 1999).

3. Normal transvaginal ultrasonography
4. Normal office hysteroscopy.
5. Normal hysterosalpingography.
6. Absence of any structural pathological findings in laparoscopy.
7. Normal male and female karyotyping.
8. Normal endocrinological profile during ovarian stimulation
9. Normal anti-cardiolipin antibody IgG, IgM and lupus anticoagulant.
10. Normal thrombophilia screen in the form of protein C, protein S, anti thrombin III, factor V mutations and factor V leiden.
11. Elevated uterine natural killer cells (uNK) density in luteal phase endometrial biopsy, defined as ≥ 5% CD16+ CD56+ cells in the stroma underlying the luminal epithelium (Tang et al, 2013; Quenby et al, 2005).
12. Normal parameters of male semen analysis according to WHO criteria 2010.
13. Written and signed informed consent by the patient to participate in the study.

Exclusion Criteria:

1. Age more than 38 years.
2. Less than 3 failed IVF cycles.
3. Poor embryo quality in previous IVF trials.
4. Abnormal ultrasonographic finding, e.g. endometrial polyps, fibroids or ovarian cysts.
5. Abnormal hysteroscopic finding, e.g. endometrial polyps, endometrial hyperplasia or fibroid.
6. Abnormal hysterosalpingographic finding, e.g. hydrosalpinx or peritoneal adhesions.
7. Abnormal male or female karyotyping.
8. Abnormal endocrinological profile during ovarian stimulation, e.g. hyperprolactinemia

9. Expected poor ovarian responders according to Bologna criteria (Ferraretti et al, 2011), i.e. presence of at least two of the following three features:

   • Presence of risk factor for poor ovarian response (POR) represented by advanced maternal age (≥ 40 years) or any other genetic or acquired conditions possibly linked to a reduced amount of resting follicles.
   • A previous POR, represented by a cycle cancelled (following the development of less than three growing follicles) or the collection of less than four oocytes in response to an ovarian stimulation protocol of at least 150 IU FSH per day.
   • An abnormal ovarian reserve test (i.e. AFC \< 5-7 follicles or AMH \< 0.5-1.1 ng/ml).
10. Positive anticardiolipin antibodies or lupus anticoagulant.
11. Positive thrombophilia screen.
12. Normal uterine natural killer cells (uNK) density in luteal phase endometrial biopsy, defined as \< 5% CD16+ CD56+ cells in the stroma underlying the luminal epithelium (Tang et al, 2013; Quenby et al, 2005).
13. Abnormal semen analysis parameters according to WHO criteria 2010.
14. Any chronic medical disorder, e.g. hypertension, autoimmune disorders, … etc.
15. Known allergy to any of the intralipid constituents.
16. Mental condition rendering the patients unable to understand the nature, scope and possible consequences of the study.