The Role of IVF in the Management of Infertility Caused by Pelvic Inflammation

Pelvic Inflammatory Disease (PID) refers to inflammation of pelvic structures including the uterus, fallopian tubes, ovaries, bowel, and the smooth membrane that lines the surface of the pelvic cavity (the peritoneum). PID follows infection which reaches pelvic structures as a result of: sexual transmission via the vagina and cervix; contamination from other inflamed structures in the abdominal cavity) appendix, gallbladder, kidneys, etc.); a foreign body inside the uterus (i.e., the intrauterine device – IUD); contamination of retained products of conception following abortion or child birth; and rarely as a result of blood-born bacterial transmission (e.g., pelvic tuberculosis which is common in developing countries but rare in the United States.

More than 1,500,000 women develop PID annually in the United States. Less than one-third of these women present with acute pelvic inflammatory disease. The remaining cases usually go undetected until the woman presents with symptoms or infertility. In fact, more that 70% of patients who undergo surgery or in vitro fertilization and embryo transfer (IVF/ET) for the treatment of infertility secondary to pelvic inflammatory disease, provide no history of acute PID. In the vast majority of cases, PID results from the sexual transmission of infecting organisms such as Neisseria Gonorrhea, and Chlamydia Trachomatis, which can in most cases readily be eradicated through appropriate antibiotic therapy.  Sexually transmitted bacteria first infect the cervix (the opening into the uterus) through which they ascend via the uterus to the fallopian tubes, ovaries, and other pelvic structures. There are several important factors which predispose women towards developing PID: The first is exposure to an infected partner; the second is exposure to infection immediately prior to menstruation.  Menstrual blood provides and excellent growth medium for bacteria, promoting their proliferation and passage via the uterine cavity into the fallopian tubes; the third is relative ill health and poor nutritional status.  It is predominantly for this reason that PID runs a more rampant course in lower socioeconomic groups; fourth is the fact that previously infected tissues are highly susceptible to re-infection; resulting in women with a past history of PID being highly susceptible to recurrent attacks. While sexually transmitted PID is certainly capable of causing endometritis (inflammation of the uterine lining) the uterus itself is not the main focus of the inflammatory process.  Cyclical shedding of most of the uterine lining with menstruation tends to remove infected tissue monthly, thereby preventing the inflammation from taking a hold and causing permanent damage to or scarring of the uterine lining (the endometrium).  The main site of inflammation following sexual transmitted PID is the fallopian tube via which other pelvic and abdominal structures may be infected. Pelvic inflammatory disease that occurs following childbirth or abortion primarily targets the uterine lining, causing endometritis.  Organisms such as Bacteroides, Peptostreptococcus, Beta hemolytic streptococcus, and E.Coli readily proliferate in the products of conception that are sometimes retained in the uterus following childbirth and abortion.  The delayed onset of menstruation after both childbirth and abortion provides an opportunity for the inflammatory process to take hold and progress, sometimes leading to the development of scar tissue in the uterine cavity (Asherman syndrome) which  fuse together or produce scarring which in nits advanced stage  completely can obliterate the uterine cavity.  Less commonly, post-childbirth and post-abortal endometritis infects the entire fallopian tube(s) (salpingitis) as well as causing partial or complete blockage, and/or spreading into the pelvic cavity. PID may also result from the use of the intrauterine contraceptive device (IUD).This most commonly occurs in cases where the device is inserted into the uterus of women concurrently infected with Gonorrhea or Chlamydia.  The IUD can act as a foreign body causing local irritation which compromises the defense mechanisms that normally protect against infection.  At the same time, the IUD string which protrudes through the cervix into the vagina may act as a “wick” via which infecting organisms gain entrance to the uterus.  As with post-abortal and post-childbirth endometritis, IUD-related uterine infection often causes scarring of the endometrial lining, utero-cornual occlusion (this is where the fallopian tube(s) leave the uterine wall), salpingitis, and inflammation of other pelvic structures.  IUD-related PID is capable of causing pelvic abscess formation, the development of peritonitis (inflammation of the peritoneum), systemic infection (septicemia), which can be life-endangering.

Acute PID

Pelvic inflammatory disease may present as an acute illness with fever, severe lower abdominal pain, accompanied by a yellow or blood stained, nonirritant, vaginal discharge and vomiting which usually prompts the woman to seek urgent medical attention.

Subacute PID

More commonly, the onset of PID is gradual, less severe, and often goes unnoticed until superimposed acute PID occurs, or chronic incapacitating symptoms prompt the woman to seek medical attention (see below).

Chronic Pelvic Inflammatory Disease

Chronic PID is a consequence of untreated or unsuccessfully managed acute and/or subacute PID. The woman usually presents with symptoms of pelvic pain, heavy and painful menstrual periods, pain with intercourse (dyspareunia) and infertility. How PID Causes Infertility Sexually transmitted PID caused by Gonorrhea or Chlamydia rapidly spreads via the cervix and uterus to the fallopian tube(s). These organs are highly specialized and are designed to promote the active passage of eggs, sperm, and embryos in a timely manner to and from the uterine cavity. They contain cells whose function is to protect and nurture eggs, sperm and embryos in transit. At their ends, the fallopian tubes have small delicate finger-like projections (fimbriae) that approximate, envelope, and “pick-up” the egg(s) from the ovary(s) at the time of ovulation. Inflammation due to Chlamydia Trachomatis and Neiserria Gonorrhea, damages and often permanently destroys the specialized lining of the fallopian tube(s) and in severe cases results in fusion of the fimbriae thereby clocking the ends of the tube(s) compromising their mobility and their potential to facilitate timely passage of eggs, sperm and embryos. Pus accumulates inside the tube(s) can pass into the pelvic cavity producing peritonitis and results in the formation of scar tissue (adhesions) which further disrupts normal pelvic anatomy as well as the relationship between the tube(s) and the ovary(ies).  This may prevent the fallopian tubes from collecting the egg(s) during ovulation. In some cases pus may collect and distend the tube(s). This pus is usually absorbed over time and replaced by clear straw-colored fluid.  The resulting, occluded, fluid-filled, distended, and often functionless fallopian tube(s) is referred to as a hydrosalpinx. As previously stated, post-abortal and post-childbirth endometritis (uterine infection causes infertility by causing uterine scarring, occlusion of the fallopian tube at its junction with the uterus, and sometimes producing infection along the full length of the tube with resultant tubal damage. Sexually transmitted PID almost invariably affects both fallopian tubes.  Even in cases where a dye x-ray test (hysterosalpingogram) or laparoscopy (a procedure where a telescope-like instrument is passed through the belly button to visualize the pelvic structures) indicates that only one fallopian tube has been infected, the other tube is almost invariably also affected. It is important to recognize that the tubes of PID victims, who seemingly have normal pelvic anatomy, oftentimes have internal scarring and/or adhesion.  This could account for the low success rate seen with tubal reparative surgeries and the high ectopic pregnancy rate (8-15%) in PID patients who subsequently conceive.

Ureaplasma Urealyticum Infection

Ureaplasma urealyticum infection is an organism which causes a relatively benign form of PID. It has been implicated as a possible cause of both infertility and early recurrent miscarriages. The organism is sexually transmitted and infects the lining of the cervical canal. It rarely produces symptoms of severe physical complications in its female victims. In men, it sometimes causes nonspecific urethritis and/or prostatitis, but in the majority of cases is asymptomatic. Recent research suggests that infection with Ureaplasma urealyticum might be capable of altering the physico-chemical properties of cervical mucus and/or cervical secretions, so that when a catheter is passed into the uterus to transfer embryos or sperm, the organisms gait entry to the uterine cavity, and produce and environment that is inhospitable to embryos.

Management

Emphasis should be placed on the prevention of PID by appropriate population screening for sexually transmitted diseases and through the promotion of condom usage in non-monogamous sexual relationships.  Acute PID should be vigorously treated with the appropriate antibiotics. Gonorrhea is usually successfully treated with penicillin derivatives, cephalosporins, erythromycin, and tetracyclines.  Anaerobic organisms such as Bacteroides and Peptostreptococcus are responsive to Flagyl, Cleomycin and in some cases to doxycycline, etc. Beta hemolytic Streptococcus and E.Coli respond to penicillin derivatives, tetracyclines, and cephalosporins. E.Coli is most often treated with the penicillin derivatives or gentamicin. PID due to Chlamydial infection responds well to doxycycline, erythromycin, and to Ciprofloxin, but will not respond to penicillin derivatives or cephalosporins. Ureaplasma urealyticum infection responds to erythromycin derivatives, doxycycline and to Flagyl. All active sexual contacts should be treated concurrently and follow up cultures should always be performed to confirm complete eradication of the disease. The pain, heavy bleeding, and debilitation associated with chronic PID often necessitates removal of the tube(s) and/or ovary(ies) and even hysterectomy, especially in women who have no childbearing aspirations. Younger women who are desirous of having a child might defer such treatment while enduring ongoing symptoms, in the hope of conceiving in the interim. The Treatment of Infertility Secondary to PID: Tubal Surgery vs. In Vitro Fertilization in the 21^st Century During the 1980’s and 90’s surgery was regarded as the mainstay of treatment for infertility secondary to PID.  Now, given vastly improved success rates, IVF is the treatment of choice for almost all forms of tubal infertility. Surgery to unblock fallopian tubes or clear adhesions resulting from an inflammatory process due to infections with gonorrhea or Chlamydia is truly an exercise in futility. The chances of pregnancy occurring following such an undertaking is less than 2% per month, and less than 25% in three years. The high incidence of ectopic pregnancy following tubal surgery (20-25%), the fact that surgery requires hospitalization, general anesthesia, pain, and a significant risk of post-operative complications, and in consideration of the statistical fact that more than 70% of patients undertaking such an escapade would ultimately need IVF anyway, there is no longer any medical justification to choose tubal surgery over IVF. To make matters worse, some women have undergone more than one attempt at surgical tubal restoration. Since second and third attempts at surgery are even less likely to result in a pregnancy than the first attempt, such practice is nothing short of a travesty.