Case 9

Villegas, Jose Bernabe GYNECOLOGY Vinluan, Joseph David Teresa Luna Wong, Deo Adiel 2007 Yague, Glenn 3rd Year-D Yang, Caprice

Dr. July 31,

Case #9

A 25 year old, single nulligravid, came for consult with her live-in partner because they finally decided to “settle down” and raise a family of their own. They have been living-in for 1 year. Her partner is a 47y.o. businessman and has a 12 y.o. son from a previous relationship. She has 2 previous casual partners. LMP: July 18-22, 2007 PMP: June 20-24, 2007 PPE: Spec. exam (+) clear mucoid non-foul discharge; IE: cervix – firm, long, closed; uterus – normal size, movable, non-tender; Adn: (-)mass (-) tenderness 1. What other information should be extracted from the history? Clinical assessment and a thorough history should be taken before the couple is subjected to investigations, both invasive and non-invasive. Above all, obtain a history of previous pregnancies and their outcomes; interval between pregnancies; and detailed information about pregnancy loss, duration of pregnancy, human chorionic gonadotropin (hCG) level, ultrasound data, and the presence or absence of a fetal heartbeat. All of these will establish the integrity of the female genital tract, its endocrine functions and its ability to sustain normal cycles to efficiently support its function of reproduction. Most importantly, question female patients about their menstrual history, frequency, and patterns since menarche, especially when considering factors that might contribute or point out to anovulation as a cause. Nonetheless, it cannot be overemphasized the importance of considering other causes of problems in reproduction whether it is endocrine – a factor that may point out to systemic conditions and immunologic factors, unexplained factors like endometriosis, problems intrinsic in the female genital tract, surgical causes like tubal injury or adhesions or just a decrease in ovarian reserves. If this is the case, then a thorough history is needed as to the history of weight changes, hirsutism, frontal balding, and acne; history of connective tissue diseases and other chronic diseases (systemic lupus erythematosus or chronic renal failure); a history of surgery involving the abdomen or the genito-urinary tract or any complications from examinations done in the past involving aforementioned systems; and especially any recalled changes in the normal pattern of menses sustained in 3 to 4 months

should be delved upon when considering issues regarding problems in fertility. Specific questions should address the issues of frequency of intercourse, use of lubricants (eg, K-Y gel) that could be spermicidal, use of vaginal douches after intercourse, and the presence of any sexual dysfunction such as anorgasmia or dyspareunia. This will more or less point out to temporal and/or pertinent external factors working outside the couple that may give us a clue on factors that may contribute, whether it be modifiable and/or can be eliminated, to problems regarding reproduction. Ask male patients about previous spermiogram results (if there is any), history of impotence, premature ejaculation, change in libido, history of testicular trauma, previous relationships, history of any previous pregnancy, and the existence of offspring from previous partners. These will establish if there can be no reason to attribute infertility on the part of the man, especially if there is a history of previous pregnancy in his part. This will only mean that there has been normal functioning from before. Now temporally speaking, when considering external factors or changes which may be attributed to increasing age, then inquire some more if the previous normal functioning has been ushered by any recent observation of changes in the functioning of the gonads like premature ejaculation, or any sudden incident of trauma. This will point out to any recent causes that may contribute to problems in fertility. Ask the couple about their history of sexually transmitted diseases (STDs) whenever considering infectious causes of infertility or any risk-taking behaviors that might predispose to the mentioned problem; surgical contraception (eg, vasectomy, tubal ligation) that might have been done in the remote past; lifestyle factors as simple as having a hectic job/day that requires long hours of work and late night overtimes that may reveal problems in making time; consumption of alcohol, tobacco, and recreational drugs (amount and frequency) which may all have side effects on the functioning of the gonads that will consequently lead to infertility; occupation that adversely expose either or both of them to hazardous chemicals, fumes, or dyes in which through inhalation or direct contact may yield the same problem of infertility; and physical activities. These may all contribute, either partly or additively, to problems of reproduction. More specifically, consider: • Age of both the partners: A woman above the age of 40 years has less than half the fertility potential of a woman of 20 years. And a man above the age of 40 years can also show a lowering sperm count, although, a man can father children for his lifetime. • Previous children: If one of the partners has children from a previous union, a rough idea of the cause of infertility can be made. • Duration of the present union: If the couple has practiced contraception at any time, if their occupations separate them for any duration of time etc.

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Frequency of intercourse – Coitus or sex must occur every 48 hours from the 8th to the 18th day of the menstrual cycle for an optimum chance at pregnancy. Too frequent coitus however is rarely a cause for infertility. Rare occasions of sex or coitus is more likely to cause infertility. Pain during intercourse: Many women avoid having sex or have irregular intercourse due to vaginal pain and may complain of infertility. Coital history : How often is coitus practiced? Is it normal or painful? Is erection, penetration and ejaculation normal? Menstrual history : Is the menstrual cycle regular? Duration of flow, amount of bleeding, pain during menses. Male partner's occupation: Constant heat can lower the sperm count. So occupations that can cause the male partner to drive long distance can cause infertility. Pesticides and certain anesthetic drugs can also lower sperm count. Previous illnesses and operations: If either of them had ever had any operations near or on the genital tracts, if either of them had ever had any infections, especially infections by the chlamydia or gonococci organisms. Family medical history of both partners: Certain conditions like diabetes, high blood pressure, thyroid diseases can be genetically transmitted and can lead to low fertility. Lubricants: Sometimes when coitus or sex is difficult due to a dry vagina, many couples use lubricants like paraffin or lanolin. Many of these lubricants have a toxic effect on sperm and prevent pregnancy. Miscellaneous: Drugs, medicines. Alcohol and smoking habits.

The aim of treatment is to remove any of the identified factors causing infertility. Both the male and female partner's should be explained about the findings and a plan of treatment evolved accordingly. Reassurance : Most couples appreciate a description of the physiological process of fertilization and conception. A sympathetic hearing of their difficulties goes a long way in decreasing the stress involved in visiting a doctor for treatment. CAUSES OF FEMALE INFERTILITY About 40% of all cases of infertility are due to problems with the female partner. Another 30% are due to problems in the male partner. The rest of the remaining 30% of cases are due either to a cause which affects both the partners, or to a cause which cannot be identified. For a pregnancy to occur, three things are vital. There are other issues involved, but these 3 are the most important. So, if the couple cannot conceive and suffers from infertility, there has to be one of these problems: • Ovulation: In a normal menstrual cycle of 28 -30 days, a woman ovulates (produces an egg from her ovary) at about the 14 -16th day.

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Patent Genital tract: The female genital tract has to be open and free of any obstructions so that the sperm can reach the egg. Adequate Male sperm: The male partner needs to have adequate sperms in his semen for pregnancy to occur.

Thus, the main causes of female infertility are Anovulation and Obstruction in the genital tract. A. Causes of Anovulation: This is the commonest cause of infertility in women, accounting for 40% of all causes. It is unlikely in women who are menstruating regularly but is not uncommon. • Age: There is a steady decline in the rate of ovulation after the age of 35 years. The rate of ovulation and successful pregnancy at the age of 40 years is almost half that at the age of 20 years. • Polycystic Ovarian Disease (PCOD): This is a condition characterized by a number of minute cysts in the ovaries and a grossly reduced ovulation rate. Ovulation may be irregular and not occur in every month. In severe cases of PCOD, ovulation may stop altogether. There is also associated hormonal imbalance with a high level of hormones like insulin and androgen in this condition. • Defects in the endocrine glands: Glands like the thyroid and the pituitary are active participants in maintaining normal fertility . Both hypo- and hyperthyroidism can cause anovulation. High levels of prolactin secreted by the pituitary is also an indicator of irregular ovulation. A high insulin level is frequently associated with PCOD. • Endometriosis: This is a condition where bits of the endometrium (inner uterine lining) grows in places other than inside the uterus. If this growth occurs on the ovary, it can cause anovulation. • Ovarian Infections / tumors: Both infections and tumors can not only physically block ovulation but can also cause hormonal imbalance leading to anovulation. • Leutenized unruptured Follicles: This is a condition where the graaffian follicles develop normally but fail to ovulate - usually because of a lack of stimulus by a low LH level. • Subclinical Adrenal Cortex Failure: The hormones of the adrenal cortex is closely linked to the reproductive process. So any problem with these hormones - either a low level or a high level - can cause anovulation. • Sex Chromosome defects: Sex chromosomal defects like XXY, XXXY, XYY etc. can cause anovulation. B. Obstruction in the Genital Tract: Obstruction can occur anywhere in the genital tract - the tubes, the uterus, the cervix or the vagina. Adhesions or scar tissue in the pelvis around the tubes can also cause obstruction and prevent the sperm from reaching the ovum to fertilize it. Tubal Obstructions – Tubal obstructions may be total or partial and may account for 20% of all cases of female infertility. Endometriosis and pelvic inflammatory diseases, usually as a result of Chlamydia

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infection are common culprits. Some important causes of tubal obstruction are: Previous infections of the tubes: Infections can occur due to abortions or previous childbirth. Common infecting organisms are S. aureus, S. pyogenes. A very common infection is by the Chlamydia trachomatis organism which causes no specific symptoms at the time of infection, but the damage it causes to the tubes are discovered only on investigating for infertility. Infections of the genital organs by N. gonorrhoea, Chlamydia trachomatis or M. tuberculosis Congenital Absence of the tubes from birth usually as a result of sex chromosomal defect.

Pelvic Adhesions – Adhesions are scar tissues formed as a result of previous infections and may affect the tubes at different regions. • Fimbrial Adhesions: Adhesions near the fimbria of the tube (part of the tube near the ovaries) may pull the tube out of its proper position and prevent ‘picking up’ of the ovum by the tube. • Peritubal adhesions: Strands of adhesions may create a mechanical barrier between the tube and the ovary. • Buried ovary: The ovary may be completely or partially buried in dense adhesions preventing ovulation or ovum pickup. Uterine Factors - Certain conditions in the uterus may affect fertilization and implantation of the ovum. • Absence of the uterus: from birth or by surgery. • Atrophy: or small size of the uterus, insufficient to support pregnancy, usually a result of surgery on the uterus or radiation. • Uterine synechia: Synechia are adhesions inside the uterus causing the two walls of the uterus to fuse together, totally or partially, thus obliterating the endometrial cavity. • Uterine tumors: Certain uterine tumors like fibroids may block the tubal opening, or prevent implantation of the fertilized ovum. Cervical Factors - Cervical factors may affect the upward movement of the sperm and prevent pregnancy. • Poor cervical mucous – The cervical mucous may be thick and impenetrable due to low estrogenic stimulation. This will act as a barrier or obstruction to the sperm. Acidic mucous or the presence of anti-sperm antibodies in the mucous can also prevent ascent of the sperm. • Loss of cervical mucous: due to surgery and amputation of the cervix, or excessive cervical diathermy. • Faulty direction of the cervix: The cervix normally faces into the posterior vaginal vault where the sperm tends to pool. In some patients, the position of the cervix may be abnormal due to faulty direction of the uterus (retroversion), uterine prolapse or cochleate uterus. • Cervical Tumors: Tumors like polyps or cervical fibroids can block the cervical canal.

Vaginal Factors: • Vaginal tumors • Vaginal septa: Vaginal septa or membranes can cause a mechanical barrier to the sperm. • Vaginal infection with purulent pus: Infections such as by the trichomonas organism is believed to cause infertility. But this is still under research and has not been proved conclusively.

INFERTILITY by Soniya Patel (Madrid 28011, Spain) 100cm x 200cm. Oil and mixed media on canvas. Commissioned art work portraying the anguish, hope, eroticism and obsession that accompanies the desperate search for an elusive child. Year 2006

2. What initial investigative procedures should be done? Semen analysis, confirmation of ovulation, and documentation of tubal patency are the basic investigations that should be performed before starting any infertility treatment. A. Semen Analysis: The basic semen analysis measures the semen volume, sperm concentration, sperm motility, and sperm morphology. Specimen collection- sexual abstinence of 2 to 3 days before semen analysis is recommended because a decrease in sperm concentration is associated with frequent ejaculation. The specimen should be delivered to the laboratory within 30 minutes to 1 hour, and should be kept at body temperature; otherwise this might alter the results. Normal seminal fluid analysis (WHO)

B. Assessment for Ovulation : •

Volume

>2 mL

Sperm concentration

> 20 M/mL

Sperm motility

>50% progressive or >25% rapidly progressive

Morphology (strict criteria)

>15% normal forms

WBC

> 1 M/mL

Immunobead or mixed antiglobulin reaction test

<10% coated

Basal Body temperature (BBT) : this is the least expensive method of confirming ovulation. The patient records her temperature each morning on a BBT chart. The body temperature is raised by progesterone (progesterone is thermogenic) and is thus higher after ovulation in the luteal phase, than in the follicular phase. The difference in temperature may be between 0.5 - 1 degrees. This change in temperature can be recorded on a chart and gives a fair indication of ovulation.

The temperature is recorded from the 1st day of the menstrual cycle. The oral temperature should be taken first thing in the morning while the woman is still in bed, before taking any food or even rinsing the mouth. There may be a sharp drop of about 0.5 degrees just at the time of ovulation. Then the temperature rises and stays more than 1 degree above the pre-ovulation temperature. If pregnancy occurs, it continues to remain high throughout pregnancy. But if pregnancy does not occur, it begins to drop again 2 – 3 days before the start of the next menstrual cycle. The BBT can be altered by lack of sleep, stress or fever. It is not very reliable in women with irregular cycles. But its advantage is that it can be done by the couple themselves in the privacy of their home. The drawback of this method is that presumptive ovulation can only be identified retrospectively, that is, it merely confirms that ovulation has occurred. •

Cervical Mucous : At the time of ovulation the cervical mucous changes from a thick consistency to a thin, watery consistency. It can be drawn out into threads more than 10 – 15 cm long. This is the Spinnbarkeit test. If the mucous is spread out thickly on a glass slide and allowed to dry, it shows a typical ‘fern pattern’ under the

microscope. Both these tests indicate a level of estrogen adequate to cause ovulation. •

Ovulation Kits (LH monitoring) : Ovulation kits are commercially available in the market to test for ovulation. Ovulation occurs 34 to 36 hours after the onset of LH surge and 10 to 12 hours after the LH peak. These kits test for the LH surge just before ovulation using ELISA (40 mIU/mL) as the threshold for detection. In 5-10% of women, ELISA test cannot detect urinary LH; serum LH is used in these cases.

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Hormone levels : If ovulation occurs, the serum progesterone level in the blood on the 5 – 8th day after ovulation (approximately 21st day of the menstrual cycle) becomes high, around 10 – 60 nmol/L.

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Ultrasonography (USG) : USG is used for real-time visualization of the gradual growth of the follicles, the number and size of the follicles and the corpus luteum after rupture of the dominant follicle. Ovulation is characterized by a decrease in size of monitored ovarian follicle and appearance of fluid in the cul-de-sac.

C. Tubal Patency Tests : •

Hysterosalpingograhpy (HSG) – the initial diagnostic test and most widely used test for tubal patency in the investigation for female infertility. HSG is usually performed between cycle days 6 and 11. During menses, HSG avoided because of incidence of vascular intravasation caused by dilation of periuterine veins. A non-irritant radio-opaque dye is injected through the cervix into the uterus. X-rays are taken of the movement of the dye through the uterus, the tubes and then the spillage into the abdominal cavity through the fimbrial end of the tubes. Any block in the passage is shown up in the X-rays. The advantage of a HSG is that not only does it reveal whether a block is present, it also reveals the position of the block in the reproductive tract, and also the presence of adhesions around the tubes.

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Falloposcopy- allows direct fiberoptic visualization of the tubal ostia and intratubal architecture. It also allows the visual identification of tubal ostia spasm, abnormal tubal mucosal patterns, and even intraluminal debris causing tubal obstruction.

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Sonohysterography with contrast media- a less invasive method of diagnosing fallopian tube obstruction; sensitivity and specificity similar to laparoscopic chromotubation.

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Laparoscopy : Dye injected into the cervix during a laparoscopy operation can be observed spilling out of the tube if patent. This is a most reliable test as it is directly visualized. Advantage of the test is that identified abnormalities such as tubal obstruction, pelvic adhesions, and endometriosis, can be treated at the time of diagnosis. Disadvantages are that it is an operative procedure and requires the patient to be admitted to the hospital for at least one day.

3. What work-ups are necessary? The following algorithms are from the National Guideline Clearinghouse’s Diagnosis and Management of basic infertility.

Additionally:

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Post-Coital test : • Sims-Huhner test : In this test, a drop of mucous is removed from the cervix not later than 12 hours (preferably within 2 hours) after coitus. The mucous is examined under a microscope for sperm and their motility, if any. The test is said to be positive, if there are at least 5 motile sperms found in the cervical mucous.

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Kremer Test : A drop of mucous at the time of ovulation is collected and placed on a glass slide. A drop of the husband’s semen is placed near it. Invasion of the mucous by the sperm is examined under a microscope. Donor semen with the wife’s mucous and donor mucous with the husband’s semen can also be used for differential diagnosis.

Hormone assays : Tests for TSH, T3, T4, prolactin level, insulin level and androgen level should be done. Conditions like hypothyroidism, hyperprolactinemia, and PCOD can cause infertility by interfering with normal ovulation. Blood tests : VDRL test, ESR for any infections, blood glucose test.

References: •

Berek, J. Novak’s Gynecology, 14th edition.

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http://www.aafp.org/afp/20070315/857ph.html

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http://www.gynaeonline.com/infertility.htm

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http://www.gynaeonline.com/causesfemaleinfertility.htm

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http://www.gynaeonline.com/investigationsfemaleinfertility.htm#investigation s

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http://www.gynaeonline.com/treatmentfemaleinfertility.htm#treatment

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http://www.guideline.gov/summary/summary.aspx?ss=15&doc_id=5567&strin g= Institute for Clinical Systems Improvement (ICSI). Diagnosis and

management of basic infertility. Bloomington (MN): Institute for Clinical Systems Improvement (ICSI); 2004 Jul. 47 p. [85 references]