A semen analysis is performed on a freshly collected specimen following a recommended three-day continence period. The numerical evaluation includes volume, pH, motility and morphology. Except for specimens with extremely low sperm counts and other compromised parameters, it is unusual for the seminal fluid to be solely responsible for infertility. Bacteria cultures are the most important component of the semen analysis. With the availability of highly sophisticated in vitro techniques, even a severely oligospermic specimen, can be successfully utilized, if it is void of harmful bacteria. In cases of complete azoospermia, donor sperm samples from reputed laboratories are used for insemination. In selected cases, varicocele repair may improve semen quality. The single, most effective therapy for improving semen quality, in our experience, is antibiotic therapy
. Since the prostate often harbors harmful bacteria that can cause structural damage, sonography has become part of a routine semen analysis. The ultrasound image helps to determine the optimal treatment approach.
The structural evaluation of the female pelvis starts with a Hysterosalpingogram. We perform this procedure at the Radiology Department of New York Presbyterian Hospital. Between day 5 and day 10 of the cycle, just prior to ovulation. Dye is injected through the cervical canal and the uterine cavity and the fallopian tubes are photographed as they fill with dye. There is no immediate need for a laparoscopy with completely normal findings. If any adhesions, tubal blockage, intrauterine pathology with congenital abnormalities are documented, we recommend laparoscopy. A modified form of this test is the sonohysterogram, and it is performed as an outpatient procedure in the office. Often the information obtained through this procedure is adequate to assess endometrial structure and tubal patency.
Laparoscopy is an in-hospital procedure, performed under general anesthesia. The abdominal cavity is inflated with carbon dioxide and a fiberoptic instrument is placed through the navel and additional instruments through entry sites in the lower quadrants. The small instruments introduced can accomplish surgical repair of pelvic pathology. History, physical examination, sonography and historosalpingography almost always reveal most pelvic pathology. If there is still a question about possible pelvic pathology, we refer patients to a skillful surgeon for this procedure. Laparoscopy can be performed as an out-patient procedure.
Postcoital Test and Mucous Slide Test
This test is performed during the time of ovulation. An ovulation predictor kit is used to predict the exact timing. When the color turns, the couple is instructed to have intercourse that night and the female partner is asked to come to the office the next morning. The test results are considered good if, after twelve hours, highly active sperm are present in a clear, cervical mucous. We do not perform the postcoital test one or two hours after intercourse since conditions, such as anti-sperm antibodies or bacterial contamination in the cervical mucous allow sperm to survive for a few hours, thus giving a falsely favorable reading. This is a highly informative test that should not be bypassed and replaced by insemination. A poor PC test is the most sensitive indicator of bacterial infections in the cervix and/or antibody production in response to these infections. The Mucous Slide Test can be performed during office visit if the appointment falls on the day of ovulation. During examination of the female, cervical mucous is collected on a glass slide and cover slip placed over it. A droplet of the husband sperm is placed to the edge of the cover slip. Through capillary action, the sperm droplet will seep under the cover slip and reach the mucous droplet. The interaction between the sperm and the mucous can be witnessed within minutes.
Transvaginal and trans-rectal ultrasonography
In the female, routine use of vaginal ultrasound has completely replaced bi-manual examination of the female pelvis. Uterine and ovarian pathology and functional changes in the ovaries and in the uterine lining can be carefully assessed with vaginal ultrasound. Vaginal ultrasound is part of the monitoring protocol during stimulation with fertility drugs, including Clomiphene, Metrodin, Pergonal and HCG. Prior to intrauterine insemination or postcoital testing, a vaginal sonogram is performed to document the presence of the ovulatory follicle. Vaginal sonography is part of the routine GYN examination and essential in the serial follow-up visits for benign ovarian cysts. A sonographic measurement of the uterine lining during ovulation makes the endometrial biopsy for staging obsolete, since a lining that measures 10mm or more, with a triple layer present, excludes a luteal phase defect. In the male, routine use of trans-rectal ultrasound helps asses prostate, bladder and seminal vesicle pathology and determine the type of therapy needed to effectively deliver antibiotics to the affected tissue.
Through this procedure, washed or unwashed spermatozoa are injected either into the cervical canal (unwashed) or into the uterine cavity (washed). A clear cut indication for the procedure is sexual dysfunction when spontaneous intercourse fails to deposit the sperm. A limited number of inseminations can be performed before IVF is offered in cases of severe oligospermia. There is much uncertainty about the actual benefit of artificial insemination with oligospermia or when it is coupled with fertility drug stimulation. To overcome a poor cervical factor, artificial insemination is legitimate only if every efforts has been made to eradicate a cervical infection that prevents spontaneous sperm migration. We do not see any rationale behind performing artificial insemination if a postcoital test is favorable. In a case of primary infertility, when a poor cervical factor is the only documented obstacle to achieve a pregnancy, there is always a danger of creating a secondary infertility condition if an infectious cervical factor is overlooked. The infection can be introduced into the previously clean uterine cavity by the procedure. Even though a single pregnancy may be achieved, subsequent pregnancies fail to occur due to this contamination process.
Fertility Drug Stimulation
In clear-cut cases of ovulatory disorders, refractory to antibiotic therapy with associated polycystic ovarian disease, there is a definite place for Clomiphene, Pergonal, Metrodin and HCG stimulation. When all other fertility procedures are exhausted and patients must turn to an IVF procedure, fertility drugs are the only option. It is contraindicated to resort to fertility drugs prior to antibiotic therapy in normally functioning females. Clomiphene and subsequently, Pergonal and Metrodin should never be prescribed before a full evaluation for bacterial infections with appropriate antibiotic therapy. Clomiphene in low doses has relatively few side-effects and there is only a remote chance that ovarian cysts will form. Pergonal, HCG and Metrodin, however, need close monitoring with serial vaginal ultrasound and blood estradiol determinations.
Antisperm Antibody Determinations
A great uncertainty exists about the exact significance of antisperm antibodies either in the male or in the female genital canal. Unquestionably, very high concentrations interfere with sperm migration or with the fertilization process. We believe antisperm antibodies are produced as a secondary phenomenon in response to bacterial infections in the genital canal; we offer antibiotic therapy as the first step. The high number of patients we have observed with diminished antisperm antibody levels following antibiotic therapy justifies this approach.
Day-2 or day-3 determination of estradiol, FSH and LH values are probably the most important predicators of good ovarian function for any cycle. Elevated levels of the pituitary hormones, FSH and LH with variable estrogen levels, suggest resistant ovaries. If genital-tract infections are documented through culture studies, especially Chlamydia trachomatis, there is an excellent chance that the levels will normalize after adequate antibiotic therapy. When Chlamydia trachomatis infects the ovaries, causing amenorrhea, the condition can be reversed with antibiotic therapy. When a sonographic examination performed during the luteal phase shows a well developed uterine lining with a triple layer present, we find that serum estradiol, progesterone determinations or endometrial biopsy during the luteal phase are unnecessary. To complete the workup, serum prolactin, thyroid hormone and adrenal hormone determinations are performed.
In Vitro Fertilization
There are either non-stimulated, natural cycle IVF procedures or Pergonal/Metrodin/HCG stimulated IVF cycles. With a natural cycle IVF, a single egg is monitored during the woman’s normal cycle and when ovulation is imminent, based on vaginal ultrasound, the egg is retrieved. The fertilization occurs in the laboratory and two to three days later, the embryo is transferred into the uterine cavity. The advantage of this procedure is that no drugs are introduced and there is essentially no limit to how many times the patient can undergo the procedure. Working with one egg, however, gives a considerably smaller success rate when compared to stimulated IVF cycles. In a stimulated IVF cycle a combination of Lupron, Metrodin, Pergonal, and HCG are used to stimulate several eggs during the first part of the menstrual cycle, which are subsequently retrieved through vaginal aspiration. The eggs are matured in the laboratory and once embryos form, the best three or four are replaced two to three days after retrieval. The disadvantages of this method include the expense, the potential side effects of the powerful drugs used and the anesthesia needed for the retrieval. Due to the availability of multiple eggs, however, the pregnancy rate is much higher than it is in natural cycle IVF. During both natural-cycle IVF and stimulated IVF, one may elect day five (blastula) transfer with an improved chance for implantation. At the MacLeod Laboratory, we have observed that most IVF cycles are performed on women whose fertility was compromised by various bacterial contaminations. We believe that the compromised pregnancy courses and neonatal outcomes associated with IVF are due to these contaminants. We therefore suspended our IVF program and now concentrate on eliminating these infections. Often, the elimination of these bacteria is enough to reverse infertility.