endometriální faktory selhání ivf 2.část

2.Receptivity of the Endometrium:

a)Contour of the uterine cavity

It has long been suspected that anatomical defects of the uterus might result in infertility. While the presence of myomas (fibroids) in the uterine wall, are unlikely to cause infertility, an association between their presence and infertility has been observed in cases where they distort the uterine cavity, or protrude as submucous polyps through the endometrial lining. It would appear that even small submucous myomas have the potential to prejudice implantation.

It is likely that any surface lesion in the uterine cavity, whether an endometrial, placental or fibroid polyp (no matter how small), or intrauterine adhesions, has the potential to interfere with implantation by producing a local inflammatory response, not too dissimilar in nature from that which is caused by a foreign body such as a intrauterine contraceptive device. Unfortunately, a hysterosalpingogram (HSG) will miss the diagnosis in approximately 20% of cases. The only reliable methods for diagnosing even the smallest of such lesions, is through the performance of a sonohysterogram (fluid ultrasound) or by hysteroscopy.

Sonohysterography [syn; Fluid ultrasonography (FUS)]
Fluid ultrasonography is a procedure whereby a sterile solution of saline is injected via a catheter through the cervix and into the uterine cavity. The fluid distended cavity is examined by vaginal ultrasound for any irregularities that might point to surface lesions such as polyps, fibroid tumors, scarring, or a uterine septum. If performed by an expert, FUS is highly effective in recognizing even the smallest lesion and can replace hysteroscopy under such circumstances. FUS is less expensive, less traumatic, and equally effective as hysteroscopy. The only disadvantage lies in the fact that if a lesion is detected, it may require the subsequent performance of hysteroscopy to treat the problem, anyway.

Hysteroscopy
Diagnostic hysteroscopy is an office procedure that is performed under intravenous sedation, general anesthesia, or paracervical block with minimal discomfort to the patient. This procedure involves the insertion of a thin, lighted, telescope like instrument known as a hysteroscope through the vagina and cervix into the uterus in order to fully examine the uterine cavity. The uterus is first distended with carbon dioxide gas, which is passed through a sleeve adjacent to the hysteroscope. As is the case with FUS, diagnostic hysteroscopy facilitates examination of the inside of the uterus under direct vision for defects that might interfere with implantation. We have observed that approximately one in eight candidates for IVF has lesions that require attention prior to undergoing IVF in order to optimize the chances of a successful outcome. We strongly recommend that all patients undergo therapeutic surgery (usually by hysteroscopy) to correct the pathology. Prior to IVF. Depending on the severity and nature of the pathology, therapeutic hysteroscopy may require general anesthesia and in such cases should be performed in an outpatient surgical facility or conventional operating room where facilities are available for laparotomy, a procedure in which an incision is made in the abdomen to expose the abdominal contents for diagnosis, or for surgery should this be required.

b) Endometrial thickness

In 1989, we were first to show that in both normal and "stimulated " cycles, preovulatory endometrial thickness and ultrasound appearance, is predictive of embryo implantation (pregnancy) potential following In Vitro Fertilization/Embryo Transfer (IVF/ET). With conventional IVF (where the woman receives fertility drugs and has her own fresh embryos transferred to her uterus), there needs to be a 9mm sagital thickness (Grade 2) and a triple line appearance (Grade A) accordingly, a Grade 2A lining is optimal in such cases. Anything less is associated with about a five- (5) fold reduction in live birth rate per ET. A possible exception may apply in cases of third party embryo Recipients (Ovum donation, IVF-Surrogacy) and in cases of Frozen embryo transfers (i.e., where the recipient receives supplementary estrogen/progesterone and not gonadotropins, to prepare the uterine lining. Here, a lining of 8mm thickness seems to be adequate.

A “poor” endometrial lining most commonly occurs in women with a history of unexplained recurrent IVF failures or early recurrent miscarriages and is usually attributable to: 1) inflammation of the uterine lining (endometrium), i.e., endometritis (occurring following a septic delivery, abortion or miscarriage, 2) adenomyosis (gross invasion of the uterine muscle by endometrial glandular tissue), 3) multiple fibroid tumors of the uterine wall) 4) prenatal exposure to the synthetic hormone, diethylstilbestrol( DES)and, 5) in women who have received clomiphene citrate (Clomid, Serophene) for at least 3 months in a row without a resting cycle (this effect is self-reversible within 4-6weeks of discontinuing clomiphene).

Hitherto, attempts to augment endometrial growth in women with poor endometrial linings by bolstering circulating estrogen blood levels (through the administration of increased doses of fertility drugs, aspirin administration and by supplementary estrogen therapy) yielded disappointing results. We recently reported on the ability of vaginally administered Viagra to significantly enhance uterine blood flow and estrogen delivery to the endometrium and thereby improve endometrial development. In the process many women with intractably poor endometrial development have achieved healthy pregnancies.