Infertility, Peritoneal Factor Case File
Eugene C. Toy, MD, Patti Jayne Ross, MD, Benton Baker III, MD, John C. Jennings, MD
CASE 56
A 31-year-old G1P1 woman presents with a history of infertility of 2-year duration. She states that her menses began at age 12 years, and they occur at regular 28-day intervals. A biphasic basal body temperature (BBT) chart is recorded. She denies sexually transmitted diseases, and a hysterosalpingogram (HSG) shows patent tubes and a normal uterine cavity. Her husband is 34 years old and his semen analysis is normal.
» What is the most likely etiology of the infertility?
ANSWER TO CASE 56:
Infertility, Peritoneal Factor
Summary: An infertile couple is evaluated. Her menses are regular, and a biphasic basal body temperature chart is recorded. She denies sexually transmitted diseases, and a hysterosalpingogram shows patent tubes and a normal uterine cavity. The semen analysis is normal.
- Most likely etiology: Endometriosis (peritoneal factor).
ANALYSIS
Objectives
- Know the five basic etiologies of infertility.
- Understand the history and laboratory tests for these five factors.
- Understand that endometriosis is more common than cervical factor infertility
Considerations
This 31-year-old woman has secondary infertility, meaning she has had a pregnancy in the past. In approaching infertility, there are five basic factors to examine: (1) ovulatory, (2) uterine, (3) tubal, (4) male factor, and (5) peritoneal factor (endometriosis). Her history is consistent with regular ovulation; this is further supported by the biphasic basal body temperature chart. The uterine and tubal factors are normal based on the normal hysterosalpingogram (a radiologic study in which dye is placed into the uterine cavity via a transcervical catheter). The male factor is essentially ruled out based on the normal semen analysis. Therefore, the remaining factor not addressed is the peritoneal factor. If the patient had prior cryotherapy to the cervix, the examiner might be directed to consider cervical factor (rare); similarly, if the patient complained of the three Ds of endometriosis (dysmenorrhea, dyspareunia, and dyschezia), then the clinician would be pointed toward the peritoneal factor. Since there are no hints favoring one factor over another, the clinician must pick the most common condition, which is endometriosis.
APPROACH TO:
Infertility
DEFINITIONS
ASSISTED REPRODUCTIVE TECHNOLOGY: Procedures in which the oocytes and/or sperm are handled in the laboratory in an effort to enhance fertilization. These include in vitro fertilization (IVF), intracytoplasmic spermatic injection, preimplantation genetic diagnosis, and other procedures.
IN VITRO FERTILIZATION: The handling of a woman’s oocyte and sperm in the laboratory environment, fertilization of the oocyte, and then injection of the blastocyst into the endometrium.
INFERTILITY: Inability to conceive after 1 year of unprotected intercourse.
PRIMARY INFERTILITY: A woman has never been able to get pregnant.
SECONDARY INFERTILITY: A woman has been pregnant in the past, but has 1 year of inability to conceive.
CLINICAL APPROACH
Infertility affects approximately 10% to 15% of couples in the reproductive age group. Fecundability, defined as the probability of achieving a pregnancy within one menstrual cycle, has been estimated at 20% to 25% for a normal couple. On the basis of this estimate, approximately 90% of couples should conceive after 12 months. The physician’s initial encounter with the couple is very important and sets the tone for further evaluation and treatment. It is extremely important that after the initial evaluation, a realistic plan be established and followed (Table 56– 1).
The five main causes of infertility are as follows:
1. Ovulatory disorders (ovulatory factor). Ovulatory disorders account for approximately 30% to 40% of all cases of female infertility. A history of regularity or irregularity of the menses is fairly predictive of the regularity of ovulation. The basal body temperature chart is the easiest and least expensive method of detecting ovulation (Figure 56– 1).
The temperature should be determined orally, preferably with a basal body thermometer, before the patient arises out of bed, eats, or drinks. The chart documents the rise of temperature of about 0.5°F that occurs after ovulation due to the release of progesterone (a thermogenic hormone) by the ovary. The rise of temperature accounts for the biphasic pattern indicative of ovulation.
Figure 56–1. Basal body temperature chart. After ovulation, the temperature rises by 0.5°F for 10 to 12 days.
Midluteal (day 21) serum progesterone level is an indirect method of documenting ovulation. Luteinizing hormone (LH) and, particularly the LH surge, can be detected with self-administered urine test kits. Ovulation occurs predictably about 36 hours after the onset of the LH surge. Other tests include the endometrial biopsy showing secretory tissue, or an ultrasound documenting a decrease in follicular size and presence of fluid in the cul-de-sac, suggesting ovulation. For women older than age 30, assessment of ovarian reserve such as day 3 follicle-stimulating hormone (FSH), or anti-müllerian hormone level testing may be helpful (see Case 30).
2. Uterine problems. The hysterosalpingogram is the initial test for intrauterine shape and tubal patency. It should be performed between days 6 and10 of the cycle. Hysteroscopy likewise provides direct visualization of the uterine cavity when the HSG suggests an intrauterine defect. Saline infusion sonohysterography can also be performed to image the endometrial cavity. Uterine abnormalities have been associated with recurrent pregnancy losses. Uterine myomata and, in particular, submucosalmyomata may interfere with implantation and fertility.
3. Tubal factor. A history of chlamydial or gonococcal cervicitis or salpingitis may point toward tubal disease. Yet, the majority of women with tubal factor infertility have no history of sexually transmitted infections (STIs), owing to the asymptomatic nature of the infections. The hysterosalpingogram is fairly accurate but not perfect. A normal test shows a thin line of dye through the tubes and spillage into the peritoneal cavity outlining the bowel. Abnormal findings should be confirmed with laparoscopy, which is considered the “gold standard” for diagnosing tubal and peritoneal disease. In addition, operative laparoscopy can provide for the treatment of tubal and peritoneal disease through a minimally invasive technique.
4. Abnormalities in the semen (male factor). The semen analysis is a very basic and noninvasive test and should be one of the initial examinations. Even men who have fathered other children should have a semen analysis. The semen should be evaluated in terms of: volume (nl > 2.0 mL), sperm concentration (nl > 20 million/mL), motility (nl > 50%), and morphology (nl > 30% normal forms). An abstinence period of 2 to 3 days prior to semen collection is recommended. One abnormal test is not sufficient to establish the diagnosis of a male factor abnormality, and the test should be repeated after 2 to 3 months (the process of transforming spermatogonia into mature sperm cells requires 74 days).
5. Peritoneal factor (endometriosis). Endometriosis, a common condition associated with infertility, should be suspected in any infertile woman. The prevalence of endometriosis ranges from 0.5% to 5% in fertile and 25% to 40% in infertile women. Fecundity, defined as the probability of a woman achieving a livebirth in a given month, ranges from 0.15 to 0.20 in normal couples and 0.02 to 0.10 in untreated women with endometriosis. The suspicion should increase if she complains of dysmenorrhea and dyspareunia, but often is present even in asymptomatic women. Although not completely understood, endometriosis may cause infertility by inhibiting ovulation, inducing adhesions, and, perhaps, interfering with fertilization. Laparoscopy is the gold standard for the diagnosis of endometriosis, and can allow for surgical ablation/ excision of the lesions. Lesions can be of various appearances, from clear to red to the classic “powder burn” color.
Current evidence indicates that medical therapy is not as beneficial for endometriosis-associated infertility. Surgical treatment in the form of laparoscopy or laparotomy is the efficacious choice with the former providing shorter hospitalization, shorter recovery, potentially less adhesions, and less discomfort to the patient. Restoration of the anatomy with excision of endometrial nodules, removal of endometriomas, and adhesiolysis is the mainstay in the treatment of advanced stages of endometriosis associated with infertility. However, despite surgical excision, conception rates seem to be less in women with extensive disease. Regardless, it seems intuitive that a structural normalization of severely distorted pelvic anatomy can improve conception outcomes, quality of life for the patient, and facilitate egg retrieval in cases of in vitro fertilization. Surgical options remain controversial in early stages of endometriosis without anatomical distortion. However, excision of early lesions can retard the progression of the disease. There is an absence of qualified evidence to indicate that fertility is enhanced with preoperative or postoperative medical therapy. The theoretical benefits do not seem to outweigh the increased costs and rates of morbidity. Medical therapy alone or in combination with surgery may only serve to delay fertility.
Assisted Reproductive Technologies
Assisted reproductive technologies now account for 1% to 2% of pregnancies in the United States. The indications include severe tubal factor, male factor, endometriosis, or unexplained or other infertility not responsive to medical therapy. IVF involves transvaginal extraction of oocytes using ultrasound guidance, typically after follicle stimulation, fertilization with sperm, and then replacement of fertilized
blastocyst(s) into the endometrial cavity through a transcervical catheter (see Figure 56– 2). Careful monitoring of the patient with serial ultrasounds and estradiol levels is important to avoid the dangerous ovarian hyperstimulation syndrome. Other complications include multiple gestation, preterm labor, and miscarriage.
Figure 56–2. IVF sequence: ova aspirated, fertilized in laboratory, and then embryo transfer performed
in this patient with tubal factor infertility.
In general, the “quality” of the oocyte is the single most important factor dictating successful pregnancy. Donor eggs can be used if the patient’s oocytes are of questionable quality. With male factor infertility, intracytoplasmic spermatic injection (ICSI) can be used, by directly injecting a single sperm through the zonapellucida and oocyte cell membrane using micromanipulation techniques. Preimplantation genetic diagnosis can be performed by removing 1 or 2 cells at the 6 to 8 cell blastocyst stage, to test for single gene disorders or translocations. Cryopreservation is often used for those fertilized oocytes that are not implanted, and can be thawed and used at a later time. Surrogates have been used for gestation. There are numerous other issues that are controversial and ethical dilemmas.
Note: Cervical factor is considered an infrequent etiology and may be suspected with thick viscid cervical mucus before ovulation. Intrauterine insemination, using a catheter to inject washed sperm through the cervix, bypasses the cervix.
COMPREHENSION QUESTIONS
56.1 A 22-year-old G0P0 woman complains of irregular menses every 30 to 65 days. The semen analysis is normal. The hysterosalpingogram is normal. Which of the following is the most likely treatment for this patient?
A. LaparoscopyB. Intrauterine inseminationC. In vitro fertilizationD. Clomiphene citrate
56.2 A 26-year-old G0P0 woman has regular menses every 28 days. The semen analysis is normal. The patient had a postcoital test revealing motile sperm and stretchy watery cervical mucus. She has been treated for chlamydial infection in the past. Which of the following is the most likely etiology of her infertility?
A. Peritoneal factorB. Male factorC. Cervical factorD. Tubal factorE. Ovulatory factorF. Uterine factor
56.3 A 28-year-old G1P1 woman complains of painful menses and pain with intercourse. She has menses every month and denies a history of sexually transmitted diseases. Which of the following tests would most likely identify the etiology of the infertility?
A. Semen analysisB. LaparoscopyC. Basal body temperature chartD. HysterosalpingogramE. Progesterone assay
56.4 A 34-year-old infertile woman is noted to have evidence of blocked fallopian tubes by hysterosalpingogram. Which of the following is the best next step for this patient?
A. FSH therapyB. Clomiphene citrate therapyC. LaparoscopyD. Intrauterine insemination
ANSWERS
56.1 D. Irregular menses usually means irregular ovulation, and therefore, infertility could most likely be attributed to an ovarian factor. The three conditions to consider are polycystic ovarian syndrome (PCOS), which is most common, hypothalamic disturbances, and premature ovarian failure (POF). Causes of hypothalamic disturbances affect pulsatile gonadotropin-releasing hormone, such as hypothyroidism and hyperprolactinemia. Thus, the evaluation of a woman with irregular ovulation usually includes checking TSH and prolactin levels. Elevated FSH levels would suggest POF. Clomiphene citrate is a treatment for anovulation, particularly polycystic ovarian syndrome. The diagnosis of PCOS is a clinical one, with characteristics of obesity, anovulation, hirsutism, and possibly glucose intolerance. A laparoscopy would be indicated if there was suspicion of a tubal factor causing infertility (such as a prior history [PMH] of chlamydia or gonorrhea) or peritoneal factor (three Ds of endometriosis). Intrauterine insemination is indicated when a cervical factor is thought to be the cause of infertility, such as thick viscid cervical mucus before ovulation. This procedure bypasses the unfavorable cervix using a catheter to inject washed sperm. The patient in this scenario does not present with symptoms consistent with cervical factor infertility. In vitro fertilization can be considered if the problem was a tubal factor or male factor.
56.2 D. The history of chlamydial infection strongly suggests tubal factor infertility. Laparoscopy would be the next step in management and is considered the “gold standard” for diagnosing tubal and peritoneal disease. The patient does not present with any of the “three Ds” of peritoneal factor, and the semen analysis is normal which excludes male factor as the cause for infertility. There is no mention of a history of fibroids, and she reports regular menses; this eliminates uterine and ovulatory factors as the etiology of her infertility.
56.3 B. This patient’s history of dysmenorrhea and dyspareunia (two out of the three Ds of peritoneal factor symptoms) suggests endometriosis, which is best diagnosed by laparoscopy. A hysterosalpingogram visualizes the inside of the uterus and would not be helpful in the diagnosis of endometriosis, since it manifests outside the uterus, tubes, and ovaries. She has menses every month; therefore, her basal body temperature chart should be normal. A progesterone assay may be used to assess whether ovulation occurs, or the adequacy of the corpus luteum (a so-called luteal phase defect).
56.4 C. This patient presents with findings suggestive of tubal factor infertility. The hysterosalpingogram (radiologic study in which dye is injected into the uterus) is not specific and should be followed up with laparoscopy; sometimes tubal spasm can prevent dye from flowing into the tubes. Laparoscopy can provide the treatment of tubal and peritoneal disease through a minimally invasive technique. Clomiphene is not effective in patients with tubal factor, and is indicated with anovulation. FSH therapy and intrauterine insemination would be ineffective for the same reasons.
CLINICAL PEARLS
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» The five basic factors causing infertility are: ovulatory, uterine, tubal, male, and peritoneal. » Irregular menses usually means irregular ovulation; regular menses usually indicates regular ovulation. In general, ovulatory disorders are fairly amenable to therapy. » A history of salpingitis or chlamydial cervicitis suggests tubal factor infertility. » Laparoscopy is the “gold standard” in diagnosing endometriosis, and lesions may have a variety of appearances. » Surgery is the main therapy for endometrial or tubal abnormalities associated with infertility. » Assisted reproductive technologies involve isolation and handling of the oocyte and procedures include IVF and ICSI. |
REFERENCES
Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in vitro fertilization. Fertil Steril. 2002;77:1148-1155.
Brown J, Farquhar C. Endometriosis: an overview of Cochrane reviews. Cochrane Database Syst. Rev, 2014.
ESHRE Endometriosis Guideline Development Group. ESHRE guideline for the diagnosis and treatment of endometriosis; 2013.
Houston DE, Noller KL, Melton LJ, et al. Incidence of pelvic endometriosis in Rochester, Minnesota, 1970-1979. Am J Epidemiol. 1987;125(6):959-969.
Lobo RA. Infertility. In: Katz VL, Lentz GM, Lobo RA, Gersenson DM, eds. Comprehensive Gynecology. 6th ed. St. Louis, MO: Mosby-Year Book; 2012:1001-1038.
Meldrum DR. Infertility and assisted reproductive technologies. In: H acker NF, Gambone JC, Hobel CJ, eds. Essentials of Obstetrics and Gynecology. 6th ed. Philadelphia, PA: Saunders; 2015:371-378.
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