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New Treatment Strategies For Repeated IVF Failures

(Endometrial scratch and use of Granulocyte-colony stimulating factor)

Endometrial Scratch

What is endometrial scratching

The lining of the uterus (the endometrium) is gently 'scratched' using a thin catheter (a fine, flexible, sterile, plastic tube) which is passed through the cervix.

Who may benefit from endometrial scratching

Our clinic offers endometrial scratching to women who have had more than two IVF, ICSI or FET cycles which resulted in a negative pregnancy test, despite having good quality embryos.

How does scratching help implantation

New research and evidence suggests that scratching the uterine lining causes a 'repair reaction' which may increase embryo implantation rates:

OThe repair process releases growth factors, hormones and chemicals. The new lining which grows after the procedure is thought to be more receptive to an implanting embryo and so increases the chances of pregnancy.

Endometrial scratching may 'switch on' the genes that are responsible for preparation of the endometrium for implantation, which increases the chances of pregnancy.

When is the best time to have the procedure

The best time to perform the endometrial scratch is at the 'day 21′ treatment planning appointment, before the IVF, ICSI or FET treatment cycle begins. In a standard 28 day cycle, 'day 21′comes just after ovulation, a few days before the woman's period is due. If her periods are infrequent or irregular, the clinical team will advise on the best time for the procedure.

How is the procedure performed

Sometimes, it may be necessary to dilate the cervix before performing a scratching. Short acting IV sedation usually suffices for this minor procedure. A thin flexible catheter is inserted through the opening of the cervix, and the uterine lining is gently 'scratched'. (Inserting and moving the intrauterine catheter up and down may cause mild abdominal cramping similar to period pain.)

Success Rates

Endometrial scratching is a new technique at MFC and we have used it for more than a 100 patients with repeated IVF failures. The pregnancy rate following this procedure has been 39% per IVF cycle. Our data suggests improvement in treatment outcomes in the group of patients who have previously had multiple failed treatment cycles.

Granulocyte Colony Stimulating Factor - Intrauterine Instillation

This drug is relatively new and promoted for use in patients with a very thin lining of the uterus (endometrium) and patients with repeated implantation failures (repeated failed IVF cycles).

The mechanism of action is similar to the scratching. Infusion of G-CSF helps in the regeneration of new endometrium and also stimulates certain factors that help in embryo implantation.

It is instilled into the uterine cavity with a thin plastic tube – no anesthesia or cervical dilatation is required. The procedure is similar to an IUI and quite painless.

It can be infused either on the day of the night trigger of hCG (48 hours before egg recovery) or during the frozen embryo cycle.

The clinic has used this for a large number of patients with encouraging results.

Platelet rich Plasma (PRP) – Intrauterine instillation

Despite progress in the field of assisted reproductive technology, still multiple embryos fail to implant. A significant percentage of in vitro fertilization failure is due to the endometrial receptivity. Implantation requires perfect coordination between a good quality embryo and a perfectly receptive endometrium (lining of the uterus). Various approaches have been used as therapeutic strategies in the investigations and management of Recurrent implantation failures such as local endometrial injury, changes in stimulation protocols, intrauterine granulocyte colony-stimulating factor before embryo transfer, blastocyst assisted hatching transfer and pre-implantation genetic diagnosis for aneuploidy.

Human endometrium undergoes significant changes during implantation. Human endometrial tissue contains receptors for growth factors, adhesion molecules, cytokines, growth factors, lipids, and other factors which are thought to enhance endometrial and embryonic development. PRP contains the growth factors and other cytokines that have positive effects on local tissue repair and endometrial receptivity. PRP could be a new treatment used for the improvement of the endometrial thickness in women with a thin endometrium. The use of PRP is considered safe because it is autologous and is derived from patient’s own blood.

Local administration of PRP could be a successful treatment in women with recurrent implantation failure (RIF) especially in cases with a thin endometrium and those with unexplained recurrent implantation failures.

Freeze-all Policy

A lot of failures with IVF in fresh embryo cycles are because of asynchrony between the follicles and the endometrium owing to the abnormally high hormone levels during the stimulation cycle. These patients do well with a freeze all policy where all embryos are frozen and then transferred in a subsequent unstimulated cycle (where the endometrium is more like a natural cycle and more physiological). There are many other indications where frozen embryo transfer gives better results such as Endometriosis, Polycystic ovaries, thin endometrium, patients with previous miscarriages or ectopic pregnancies and patients .

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