For optimal success in IVF the couple should undergo a meticulous (medical) evaluation prior to the IVF cycle. Components of such an evaluation are discussed in this section.
(1) Evaluation of the uterine cavity prior to the IVF cycle
The physician (and the infertile couple planning IVF) decides on what testing of the uterine cavity is desirable and which lesions (abnormalities) should be repaired to optimize success with IVF.
There is general agreement among infertility specialists that some assessment of the uterine cavity is important prior to IVF. About 5% of unselected females in the population have a uterine anomaly (irregularity such as a septate uterus) and an additional 10% of these women have intracavitary lesions (such as endometrial polyps or fibroids). These abnormalities could lead to a marked elevation in spontaneous pregnancy loss (miscarriage) and often can be (easily) repaired with hysteroscopy (same day surgery). Therefore, the potential benefit of identifying such lesions prior to an IVF cycle is tremendous.
The three most popular techniques used to identify lesions in the uterine cavity are hysterosalpingography (HSG), hysteroscopy and sonohysterography.
The HSG does not always correlate with findings at hysteroscopy, with up to 20% of findings on HSG not being found at hysteroscopy (HSG’s false positive rate) and up to 35% of subtle lesions identified at hysteroscopy not being identified at HSG (HSG’s false negative rate). Therefore, 1 of 3 women with a normal HSG reading will have a lesion identifiable with hysteroscopy and 1 of 5 women with an abnormal HSG reading will have a normal hysteroscopy.
Hysteroscopy is the “gold standard” test for assessing the uterine cavity since there is direct visualization of the uterine cavity. I usually recommend this procedure prior to an IVF cycle. I often recommend an HSG prior to hysteroscopy in order to identify major intracavitary lesions or tubal pathology so that these can be discussed with the couple prior to surgery (allowing the fertility surgeon to preoperatively understand the couple’s desires with regard to repair).
Sonohysterography is a technique that involves injecting about 3-10 cc of fluid (usually saline) into the uterine cavity while examining the cavity (and tubes) using transvaginal ultrasonography. This procedure is highly operator dependent (a good test in some hands and a poor test in others). While sonohysterography can provide outstanding images of uterine cavity abnormalities it is (seemingly) limited in its ability to evaluate the fallopian tubes. I have not commonly used this procedure for assessing the uterus prior to IVF.
In my opinion (and that of many infertility specialists), any identified lesion of the uterine cavity should be treated prior to an IVF cycle to optimize reproductive success. This would include submucosal myomas, endometrial polyps, a uterine septum, and intracavitary adhesions.
(2) Assessment of ovarian reserve
Tests assessing decreased ovarian reserve have been correlated with reproductive success (pregnancy rates) at the time of In Vitro Fertilization. This information is not difficult to obtain and may be very useful, so most infertility specialists (including myself) encourage an assessment prior to an IVF cycle.
Unfortunately, many infertile couples are told that if their ovarian reserve is decreased then they have a marked reduction in reproductive potential (in general). This may not be the case. The tests that assess ovarian reserve have really only been thoroughly studied in the context of controlled ovarian hyperstimulation (with either IUI or ARTs). There is very little information available addressing the meaning of these test results in the normal fertile population or the bulk of the infertile population. Therefore, general statements regarding reproductive potential based solely on these test results should be discouraged.
(3) Antisperm antibodies
Presence of antisperm antibodies (ASAs) in the female partner can interfere with fertilization during IVF if her serum is used within the embryo culture medium as a protein source (a popular practice). Also, ASAs can be present within follicular fluid so that additional washes of the retrieved eggs and incubation with additional numbers of sperm may be useful.
Male (IgG and IgA) ASAs having a greater than 70% binding have been correlated with an elevated percentage of fertilization failure, so many programs either try to inseminate with about 50,000 antibody free sperm (if there is 90% binding you need 500,000 sperm to have 50,000 antibody free sperm) or proceed directly to ICSI.
The available research suggests that there are reduced pregnancy rates and possibly higher spontaneous pregnancy loss (miscarriage) rates in women with anti-chlamydia antibodies. It also appears that the endometrial lining of the uterus can have an active chlamydia infection even in the presence of negative cervical cultures (in one study 40% of women were found to have an active chlamydia infection using the highly sensitive technique of polymerase chain reaction = PCR despite negative cervical cultures and DNA probes). Routine (empiric) treatment of both partners with a 7-14 day course of doxycycline has therefore been adopted by many ART programs.
(5) Trial embryo transfer
Measuring the depth of the endometrial cavity and mapping the route required to negotiate the cervical canal is very useful prior to the actual embryo transfer procedure. The tremendous importance of an atraumatic (effortless) embryo transfer is appreciated by most infertility specialists who routinely perform ARTs. I routinely attempt to pass my preferred catheter into the uterine cavity prior to the actual day of embyro transfer, and if entry of the catheter is impossible, I determine which catheter to use at the (actual) embryo transfer.
(6) Removal of tubal hydrosalpinges
Several (recent) reports have demonstrated a marked reduction (greater than 50%) in pregnancy rates following IVF if there are hydrosalpinges (dilated fluid filled fallopian tubes) present compared to women with pelvic disease without hydrosalpinges. The success rate of IVF is suggested to return to normal if tubal repair or salpingectomy (removal of the fallopian tube) is performed on these hydrosalpinges. I strongly recommend either repair, tubal ligation or salpingectomy for women with hydrosalpinges who are considering IVF. If surgical repair is performed and the couple fails to get pregnant with less aggressive management, then I perform a hysterosalpingogram immediately prior to IVF to confirm continued patency of the tubes. If either repaired tube is blocked (with an hydrosalpinx) then I suggest removal of the tube prior to IVF.
The association between endometriosis and IVF pregnancy rates is controversial since there is a lot of conflicting data in the literature.
The dark brown (“chocolate”) fluid that might be aspirated from an ovarian endometrioma is generally thought to be embryotoxic and therefore is usually kept separate from follicular aspirates that contain eggs. Continued use of the “chocolate” lined aspiration needle is also controversial and many fertility specialists will either change needles or flush the needle a few times with media to remove this material.
The utility of a pre-IVF course of lupron (1-3 months) is unclear, with some reports suggesting a significant improvement in success with pretreatment using a GnRH agonist. Routine use of depo-lupron is not (to my understanding) commonly used by ART programs.
In one study conducted at one of the best IVF programs in the USA there was no significant difference in the observed IVF success rates between the different stages of endometriosis. Others have suggested that greater stage endometriosis might reduce implantation rates or result in an unexplained failure of fertilization. It will be interesting to see the results of future research on this topic.
(8) Frozen “back up” sperm sample
I encourage the couple to provide a sperm sample to be frozen as a back up in the event that the husband is not available to provide a specimen on the day of egg retrieval or has difficulty providing a specimen on this day. I remember one couple who elected to not provide a backup specimen, the husband was involved in a motor vehicle accident the day prior to egg retrieval, and the wife was not able to obtain a sample from her husband since he was in traction at the local hospital. In unusual cases like this, a back up sperm sample is very helpful.
Smoking results in a dramatic decrease in pregnancy rates with IVF and an increase in spontaneous pregnancy loss (miscarriage) rates. I strongly suggest discontinuation of cigarettes at least a month prior to starting an IVF cycle and many ART programs absolutely require that the woman quit smoking prior to the ART cycle.