A Couple s Guide to Infertility (Eric Daiter, MD Board Certified in Reproductive Endocrinology and Infertility)

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1 A Couple s Guide to Infertility (Eric Daiter, MD Board Certified in Reproductive Endocrinology and Infertility) The goal of this guide is to provide a medical expert s answers to the common questions: Do I have infertility? What causes infertility? How are specific problems with fertility diagnosed? Which treatments for infertility are successful and what are their risks? o Decisions, decisions, decisions o Successful ovulation treatments o Successful male factor (sperm) treatments o Successful pelvic factor treatments What options exist if all of the infertility testing and treatments do not successfully result in a pregnancy? Do I have infertility? Couples have their own expectations on how quickly a pregnancy should occur, usually based on a combination of personal, family, community and cultural beliefs. When these expectations are not met, a concern about infertility often develops. Medical scientists have studied normal human fertility rates by looking at the number of months (or ovulation cycles) from stopping contraception to achieving a pregnancy (called time to pregnancy or TTP), using large amounts of data compiled from several different countries around the world. These scientists at the World Health Organization discovered that 85% of couples would achieve a pregnancy on their own within 12 months of intercourse without contraception. One year of unprotected intercourse without a spontaneous pregnancy has become the basis for the standard medical definition of infertility.

2 The American Society of Reproductive Medicine re examined this definition in 2008 and suggested that an infertility evaluation should be considered after 6 months of unprotected intercourse without a spontaneous pregnancy in couples where the woman is 35 or more years old. They identify a general decrease in fertility rates with increasing maternal age, making early diagnosis and treatment especially important for women at least 35 years of age. Many couples already know that they have a fertility problem, based solely on their own histories. These couples can seek medical advice on fertility without 6 12 months of unprotected intercourse. Examples include but are not limited to the following list. If a woman does not have menstrual cycles or has highly irregular menstrual cycle intervals with only a few cycles per year, then she should anticipate a problem getting pregnant. A reproductive age woman will normally ovulate each month and have monthly menstrual intervals if she does not become pregnant. A woman with signs of impending menopause, such as increasingly irregular and longer menstrual cycle intervals and hot flashes, should have her egg reserve checked by an infertility expert with blood work or an ultrasound. A woman with a prior tubal ligation, who currently desires to become pregnant again. A woman with extensive pelvic surgery for such problems as endometriosis, pelvic adhesions, fibroids, and ovarian cysts may have reduced fertility or an increased chance of an ectopic pregnancy. A woman with previously identified pelvic problems such as large fibroids, blocked fallopian tubes, prior sexually transmitted disease (which often damage the fallopian tubes), ovarian cysts, endometrial polyps, or scar tissue in the uterus or pelvis. A man with a prior vasectomy, trying to have a baby. A man with prior chemotherapy or radiation therapy for cancer. What causes infertility? Identifiable causes of infertility can be grouped into female egg issues (including problems with ovulation, irregular menstrual cycles intervals, hormonal imbalances), male infertility (including low sperm count, abnormal sperm motility or shape, decreased sperm function), and female pelvic problems (including blocked or damaged fallopian tubes, endometrial polyps, scar tissue, endometriosis). Unexplained infertility is when the cause of infertility is not yet identified. The cause for infertility remains unexplained in only about 5 10% of couples after a thorough evaluation has been completed, so completion of all available diagnostic tests is often very helpful. Most medical research concludes that roughly one third of infertility problems are entirely a female problem, one third are entirely a male problem and one third are a combination of male and female problems. Therefore, assumptions regarding the likely causes (for example, I m sure it is his fault or it s probably her fault ) are often misleading and a thorough evaluation really needs to be completed to identify the actual problems.

3 (Caption: Recognized causes of ovulation dysfunction may involve the ovary, the pituitary gland, the hypothalamus or the central nervous system. This drawing of a mature ovarian follicle containing an egg only lists ovarian causes for ovulation problems) Common female causes of infertility include (1) ovulation disorders that may result from stress, including emotional stress or physical stress due to excessive exercise, starvation or binge dieting, hormonal imbalances involving the thyroid gland, excessive prolactin secretion or excessive androgenic hormones, dietary intake of large amounts of estrogen containing foods, certain medications, prior ovarian or pelvic surgery, injury to the ovary

4 (Caption: Pelvic factor infertility can include any condition or event that interferes with the ability of an egg to meet a sperm (normally within the fallopian tube) or the subsequent implantation of a resulting embryo (fertilized egg). Generally, a mature egg develops within an ovarian cyst (follicle) and normally is released into the pelvis at ovulation (#1). Sperm is released into the vaginal vault during sexual intercourse (#2) and during or shortly after intercourse some of the sperm will move from the semen into the cervical mucus (#3). The sperm cannot survive in the vagina due (largely) to a difference in ph (acidity) between semen (alkalinic) and the vaginal canal (acidic). Sperm that has successfully moved into the (more friendly) cervical mucus then travels up to the fallopian tube periodically looking for eggs. Human fertilization normally occurs in the fallopian tube (#4) and the pre implantation embryo subsequently enters the uterine cavity. Implantation normally occurs within the uterine cavity (#5).) and (2) pelvic disorders that may result from scar tissue or damage to the fallopian tubes or uterine cavity as a result of inflammation due to infection, endometriosis, ruptured ovarian cysts, pelvic surgery, or the presence of foreign materials; fibroids,

5 persistent nonfunctional ovarian cysts, endometrial polyps (Caption: Recognized causes for abnormal sperm production or function may involve the testes, the pituitary gland, the hypothalamus or the central nervous system.) Common male causes of infertility include (1) abnormal sperm production or function possibly resulting from undescended testes at birth, bladder surgery as a newborn, a varicocele, genetic abnormalities, poor dietary habits, excessive use of tobacco or alcohol or drugs, exposure to environmental toxins such as heat or some chemicals, certain medications and (2) problems with the delivery of sperm at intercourse possibly related to erectile dysfunction,

6 premature ejaculation, blockage within the vas deferens or urethra tubes that allow transport of testicular sperm from within the scrotal sac through the pelvis and penis How are specific problems with fertility diagnosed? For couples with difficulty getting pregnant, with no previously identified cause, I start with a thorough medical history, including any history of irregular menstrual cycles or pregnancies. Then I often suggest four basic diagnostic tests that are relatively affordable, low risk, easy to perform, and provide a lot of valuable information. The woman s blood is checked for hormone imbalances (that can lead to problems with the eggs that are released at ovulation) and ovarian reserve (the relative supply of eggs remaining in the ovaries that are able to be fertilized and might result in a successful pregnancy). This blood work is ideally performed on menstrual cycle day 2 4, where cycle day 1 is the first day of heavy flow. The man s semen is checked for several variables including sperm concentration, sperm motility and the shape (morphology) of the sperm. A semen analysis is very informative, however, it cannot provide very reliable information about sperm function (the sperm s ability to fertilize an egg).

7 The woman s cervical mucus is examined several hours after having sex to determine whether the sperm within the mucus is moving normally. For several days prior to ovulation, sperm usually lives comfortably within the cervical mucus for several days after intercourse and travels periodically up to the fallopian tubes to attempt to fertilize an egg. A hostile cervical mucus and sperm relationship can result in few or no sperm being able to travel to the fallopian tubes to fertilize the egg.

8 (Caption: The timing of the postcoital test within the menstrual cycle is important, since the ability of sperm to survive within cervical mucus is normally dependent (indirectly) on the circulating concentrations of ovarian hormones. Ideally, the postcoital test will be performed 1 2 days prior to ovulation. The postcoital test should (ideally) not be performed within 4 hours of intercourse (relations, sex) since complement mediated immobilization of sperm takes about 4 hours to maximally develop. Sperm is thought to live in mucus for up to 2 3 days, so the postcoital test can be performed greater than 10 hours after intercourse. A vaginal speculum is inserted and the cervix is centered. A syringe or catheter is usually placed into the cervix and (a sample of) mucus is withdrawn. This mucus is then immediately placed onto a slide, a coverslip applied, and the sample viewed under a microscope for identification of motile sperm. The grading of the postcoital test is controversial. Most often, greater than 5 progressively motile sperm per high power field (400 X magnification) is considered normal. This test is not particularly uncomfortable (generally similar in discomfort to a pap smear).

9 A hysterosalpingogram (HSG) is performed between cycle days This HSG test uses x rays to provide information about the uterine cavity (including the presence of scar tissue, endometrial polyps or fibroids within the cavity) and the fallopian tubes (including any blockages, dilatation, abnormal spillage). I offer to perform the HSG test myself for any of my ongoing patients since they rarely have discomfort when I perform the test, I can make adjustments during the test to obtain the most amount of information, I get immediate results that I can review with my patients, and the test often costs less. (Caption: This exam is usually done within a radiology suite that is equipped with an x ray machine capable of flouroscopy and a monitor (to view the study in progress from beginning to end). A speculum is placed within the vaginal vault and the cervix centered. A catheter with a balloon tip can be fed through the cervix into the uterine cavity or the anterior lip of the outer cervix can be grasped with a tenaculum (a grasping instrument) while an acorn tip catheter is inserted into the external os (opening) of the cervix (gentle pressure is applied to the cervix). Once the vaginal instruments are in place, the patient may be repositioned, flouroscopy is turned on and

10 radio opaque dye (liquid that can be visualized by xray) is slowly injected into the uterine cavity so as to outline the cavity and any filling defects (usually polyps, submucosal fibroids, or adhesions). Prior to injection of dye, the catheter should be flushed with dye to limit the number of air bubbles that are injected into and seen within the uterus. The dye should normally then be seen entering, filling and spilling from the fallopian tube(s). If the fallopian tube does not fill with dye, this identifies a proximal tubal occlusion, which can often be corrected with proximal tubal catheterization. If there is no spill from the distal end of the fallopian tube, it is important to distinguish a dilated (inner) tube (hydrosalpinx) from a normal appearing tube. If there is spillage of dye from the distal end of the fallopian tube this fluid normally moves freely throughout the pelvis. If there is loculated flow of dye into the pelvis, this suggests peritubal adhesions. When the initial entry of dye into the uterine cavity is slow, there is greater ability to visualize subtle abnormalities within the uterine cavity and there is (very significantly) less patient discomfort. This test can be very uncomfortable if the operator is not careful or experienced. Therefore, I typically offer to perform this test myself for all of my patients having the procedure. My patients rarely have significant discomfort with this test. I order prophylactic antibiotics for all of my patients undergoing hysterosalpingogram to limit the possibility of reactivation of a dormant infection within the reproductive tract. This is especially important for women with a history of prior tubal damage or infection.) Any abnormalities that are revealed by these diagnostic tests are discussed along with their appropriate treatment options. If the results from these initial basic tests are all normal, or the treatments for test abnormalities do not result in restored fertility, then further diagnostic testing is indicated. Many pelvic abnormalities, including endometriosis and pelvic adhesions, may be suspected by a woman s symptoms or medical history, but can only be diagnosed by direct visualization. A pelvic evaluation with laparoscopy and hysteroscopy is minimally invasive day stay surgery (an overnight stay in the hospital is not necessary) and can identify and treat most pelvic pathology that causes reduced fertility. The success of this surgery at restoring reproductive potential largely depends on the skill of the surgeon, so tremendous care should be exercised when choosing your doctor to perform this procedure. I believe finding a board certified Reproductive Endocrinology and Infertility specialist is a good start, when available, and finding one that specializes in pelvic repair rather than focusing their clinical practice primarily on IVF can also be very helpful. If the pelvic evaluation is normal, or an experienced and skilled reproductive surgeon repairs the pelvis without restoration of fertility, then treatments for unexplained infertility are usually appropriate. These treatments can include the use of ovulation enhancing medications during controlled ovarian hyperstimulation (attempting to produce several mature eggs per ovulation cycle) coupled with either intrauterine insemination (IUI) or in vitro fertilization (IVF). Which treatments for infertility are successful and what are their risks? 1) Decision, decisions, decisions

11 There are many different treatment alternatives for infertility. Therefore, several important decisions should be considered prior to choosing the most appropriate treatment, including The treatment should always fit the diagnosis. This is extremely important but is often overlooked. For example, ovulation problems have different treatments than male factor infertility or female pelvic abnormalities. Far too often, I hear that a treatment designed to treat one specific problem is being used to treat an unrelated problem. In vitro fertilization (IVF) should not be used as a panacea (universal treatment) for all infertility problems. Specific treatment directed at an identified problem (whether an ovulation problem, male factor, or pelvic problem) is often more effective, less expensive, and has less overall risk. IVF is a wonderful and effective treatment when it is selected appropriately. Sometimes you need to decide whether to fix it, replace it, or effectively go around it. This is particularly true when a pelvic problem is encountered. Pelvic repair may restore fertility but involves surgery and success often depends on the skill of the surgeon. IVF is a procedure that can often successfully circumvent ( go around ) an existing pelvic problem (such as a prior tubal ligation or pelvic damage that is not repairable), but generally IVF does not repair any pelvic abnormalities and the couple needs to be comfortable with this type of procedure. Generally, I attempt to identify pathology (problems) and specifically suggest repairing or treating those problems. My outlook is that if I can successfully identify and repair the abnormalities causing reduced fertility then the couple s natural reproductive potential will be restored. Treatment for infertility can differ in terms of cost, character (more or less artificial or natural in character), and medical risks. 2) Ovulation treatments When a woman has very irregular or no naturally occurring menstrual cycles, there is generally a problem with egg development (maturation). In addition, many women with regular menstrual cycle intervals can have problems with their eggs. Therefore, it is routine to assess ovulation with a thorough history, blood work directed at hormonal imbalances (that may result in an ovulation dysfunction) and egg reserve, and ultrasound examinations. If blood work and ultrasound exams are not accessible, then a complete menstrual and medical history is fairly reliable. The first line of treatment for an ovulation problem is treating an identified underlying cause, such as physical or emotional stress, through guided therapy; a hormone imbalance, such as those involving thyroid or prolactin concentrations, which can often be treated effectively with medication; dietary intake of large amounts of food containing hormones, especially estrogen like compounds, which can be removed or reduced from the diet; and medications that can effect ovulation, which can often be adjusted or changed to similar medication with less effect on ovulation. If the underlying cause of the ovulation problem is not identifiable, or if it is identified and treated without restoration of normal ovulation, then ovulation induction with medication is usually warranted. The two types of medications that are available and effective are Clomiphene citrate (Clomid, Serophene), a pill taken as 1, 2 or 3 pills a day for 5 days. This medication is not expensive, requires little monitoring and has few severe complications.

12 Clomiphene citrate can restore significantly more regular menstrual cycle intervals in about 85% of women, and is often used as a first line treatment for women with polycystic ovarian syndrome and women with presumed stress related ovulation problems (when an adequate egg reserve has been demonstrated). The main side effects include hot flashes, abdominal discomfort, breast tenderness, and moodiness. Complications include multiple pregnancy (twin rate is less than 10% and triplets are uncommon), ovarian cyst development (possibly with significant abdominal distension and pain), or abnormalities of the cervical mucus (which may reduce the sperm s ability to fertilize the egg in the fallopian tube). Injectable monotropins or gonadotropins, which contain FSH to stimulate the development of eggs within ovarian follicles. These medications are generally very expensive, require significant monitoring with blood work and ultrasounds, and have some possible severe complications. Menotropins and gonadotropins are very effective and result in successful egg maturation in up to 90% of women who failed to induce ovulation using clomiphene citrate. Also, since these medications often produce several mature eggs per cycle, there are more targets to try to fertilize per cycle. Therefore, injectable medication cycles can also be used for many male factor problems and some pelvic problems. The medications have no common side effects but complications include multiple pregnancies (twins may be as high as 25% of pregnancies and triplets (or more) in up to 5% of pregnancies), ovarian hyperstimulation syndrome with significant fluid shifts (bloating and dehydration) and pelvic pain, and rarely ovarian torsion (twisting of the ovary).

13 If these medications are ineffective or do not result in a pregnancy, it is possible to also consider donor eggs along with in vitro fertilization. With donor eggs, the chromosomes are those of the female egg donor and not those of the female trying to conceive, so the infertile couple must consider the importance of this fact carefully. Donor eggs should only be used if the couple trying to conceive is comfortable with their use. When donor eggs are used, the eggs are most often retrieved from the egg donor, fertilized in vitro with the husband s sperm, and transferred into the wife s uterus so that she can conceive and carry the pregnancy. This treatment is usually extremely expensive, can result in a child carrying a genetic abnormality from the egg donor (even if there is a normal chromosomal analysis since these tests do not discover all genetic diseases), and can result in an infection from the egg donor to the embryo recipient. Although the egg donor is thoroughly tested for most infections prior to the procedures, the eggs are fertilized immediately after retrieval without a 6 months quarantine (as with donor sperm) to allow for further infectious disease testing. Male (sperm) factor treatments When a man is found to have abnormal sperm production or function, most often by semen analysis, I routinely obtain a thorough medical history and blood work for the hormones that are involved in normal sperm production. Ideally, treatment can be directed at an identified underlying cause. Although these are less commonly identified than with ovulation dysfunctions, examples of treatable causes of abnormal sperm include:

14 narcotic drug use or abuse, which can be modified or eliminated, pituitary FSH or LH secreting tumors, which can be treated surgically if they are looked for and identified, hemochromatosis, an excess in circulating iron, which is a very rare cause of sperm abnormalities, exposure to excessive heat, including that due to a varicocele, frequent long hot baths, or sitting on heated seats for long periods of time, cigarette or alcohol abuse, which can be reduced or eliminated, medications or foods containing anabolic steroids and some other medications, which can often be eliminated or changed to other effective medication that does not have a significant impact on sperm production If no underlying treatable cause is identified, or if the treatment of all underlying causes does not result in restoration of normal sperm production, then several alternatives are available. Intrauterine insemination (IUI) is a relatively simple office procedure that places sperm directly into the uterine cavity, next to the opening of the fallopian tube, at the time of ovulation and effectively bypasses the need for sperm placed within the vaginal vault to enter and cross the cervical mucus into the lower uterine cavity. This IUI procedure essentially delivers the available sperm to the end of their natural journey through the female reproductive tract and therefore increases the likelihood that this sperm will find and fertilize an egg within the fallopian tube. The IUI procedure requires sperm washing, which removes the active sperm from the liquid semen (since the semen has components that cause severe uterine cramping). IUI is often successful in couples with a mild to moderate male factor. IUI should be relatively inexpensive, for example, at my office the procedure only costs 200 dollars. Intrauterine inseminations are also safe, with the major concern being an increased chance for transmission of an unrecognized infection from the husband to the wife (since the infectious organism may survive the washing procedure and it might be able to cross the wall of the uterine cavity more efficiently than the wall of the vaginal vault).

15 (Caption: Sperm collected by manual ejaculation into a clean container is processed (washed) to remove the sperm from the semen (liquid) and this sperm is then resuspended in an inert buffered media that is safe to place within the uterine cavity. Unwashed (whole) semen with sperm is (generally) not placed within the uterine cavity since the semen contains molecules called prostaglandins that may cause severe uterine contractions (cramps). To perform the insemination, a speculum is placed into the vaginal vault, the cervix is centered so that the opening of the os is clearly seen, washed sperm within media is drawn up into a sterile catheter and syringe (the usual volume of media for insemination is 0.5 ml), the tip of the catheter is slightly bent to negotiate the (occasionally tortuous) course through the cervical canal, and the catheter is gently fed into the uterine cavity. Once inside the uterus, the sperm and media is slowly injected into the cavity. Discomfort or cramping is (in my experience) rare with intrauterine insemination) Injectable menotropins or gonadotropins along with intrauterine insemination (IUI), where the female partner is injected with FSH containing medication for several days in order to produce multiple mature eggs (potential targets for the sperm to fertilize) and IUI is performed around

16 ovulation (to deliver active sperm closer to the eggs). These cycles of controlled ovarian hyperstimulation can effectively increase pregnancy rates, however, these medicated cycles are generally very expensive, require frequent monitoring with blood work and ultrasounds, and have risks. The major risks of an injectable medication cycle (controlled ovarian hyperstimulation) include multiple pregnancies (the twining rate is about 25% per pregnancy and the triplet rate may be as high as 5% per pregnancy), hyperstimulation syndrome (uncommon with close monitoring but can involve dehydration and abdominal bloating as a result of major fluid shifts within the body), and twisting of the ovary (rare but can cause severe pain if the ovarian torsion cuts off the ovaries blood supply). Assisted fertilization with intracytoplasmic sperm injection (ICSI), places sperm through the outer wall of the egg directly into the egg s cytoplasm, resulting in successful fertilization and the development of a normal pre implantation embryo about 70% of the time. The sperm must be living, but otherwise, the success of ICSI is largely independent of sperm quality (even immature sperm heads without tails can be used as long as they are alive). ICSI requires IVF (in vitro fertilization) and is generally extremely expensive. The risk specific to ICSI includes the possibility of passing along a Y chromosome abnormality (that resulted in the male partner s abnormal sperm production) if the offspring is also male. Studies currently available (2012) have not identified any other congenital abnormality that is increased in offspring born following ICSI. (Caption: Intracytoplasmic sperm injection, ICSI, uses a very thin glass needle to pick up one microscopic size sperm and inject that sperm cell through the zona pellucida (shell of the egg) and the cell membrane directly into the cytoplasm of the egg)

17 If these treatments are inaccessible or they do not result in a pregnancy, then anonymous donor sperm is commonly available. This donor sperm is generally frozen and quarantined for at least 6 months while the donor is evaluated for infectious diseases, so it is a bit less efficient compared to fresh sperm in terms of fertilizing eggs. The use of donor sperm also means that the male partner s genetic heritage will not be passed on to the offspring. Donor sperm varies in cost, largely depending on the available supply for specific samples. Donor sperm is usually delivered into the uterine cavity by IUI and it does not have known risks in terms of increased birth defects or miscarriages. When there is a problem with the delivery of sperm at intercourse then IUI is usually effective at delivering motile sperm into the uterine cavity. Pelvic Abnormalities A pelvic factor problem with either egg fertilization within the fallopian tube or embryo implantation into the uterine cavity is often suggested when there is a fertility problem in a couple with regular menstrual cycle intervals and a normal semen analysis. Essentially, if a couple is infertile and the eggs and sperm appear to be normal, then a pelvic problem is likely. I routinely suggest a hysterosalpingogram (HSG, to evaluate the uterine cavity and to determine whether the fallopian tubes are open) and a postcoital test (to assess whether the sperm is comfortable within the cervical mucus) for all patient couples with difficulty conceiving. When the hysterosalpingogram reveals an intrauterine filling defect (submucosal fibroid, endometrial polyp, scar tissue) or abnormal fallopian tubes (blocked, dilated, or irregular tubes) then these abnormalities should be repaired. A talented Reproductive Surgeon can usually repair the problem with laparoscopy or hysteroscopy, which are minimally invasive same day surgical procedures that have low risk and rapid recovery periods. If the repair is successful, natural reproductive potential is often restored. If the repair is not performed, then trying to go around the problem with IVF is often unsuccessful or has limited success since these ongoing problems can reduce embryo implantation. An exception is when the female partner has had a prior tubal ligation and now has a normal uterine cavity with blocked tubes on HSG. These women are often very successful at conceiving with IVF. When the postcoital test determines that the sperm cannot survive and move normally within the cervical mucus, then timed intrauterine inseminations (IUI) will deliver the motile sperm above the level of the mucus directly into the uterine cavity and this should restore fertility (assuming all other factors are normal). The IUI procedure is a low cost office procedure with few risks. If the hysterosalpingogram (HSG), postcoital test, ovulation tests and semen analysis are normal, or all identified abnormalities have been treated and the couple cannot successfully conceive, then the cause of infertility remains unexplained. In this situation there are two main treatment alternatives, one designed to further investigate the possibility of an unrecognized pelvic factor and the other to circumvent (go around) a possible pelvic factor. Pelvic evaluation with two minimally invasive minimal risk same day surgical procedures, laparoscopy and hysteroscopy, to further investigate the pelvis for abnormalities that could not be detected using the previously completed diagnostic tests. Problems that can often be found during a pelvic evaluation (laparoscopy and hysteroscopy) include endometriosis, pelvic adhesions (scar tissue), nonfunctional ovarian cysts, fimbrial agglutinations, and small defects within the uterine cavity (that can not be seen by hysterosalpingography). An experienced

18 talented Reproductive Surgeon can successfully treat most of these abnormalities with restoration of reproductive potential so choose this surgeon carefully. These procedures may also result in decreased menstrual pain, irritable bowel symptoms (like diarrhea or constipation) during menses, and elimination of abnormal uterine bleeding (such as menstrual spotting before or after the menstrual flow). In my experience, these procedures are almost always covered by medical insurance so the out of pocket cost for a patient is minimal. The amount of risk involved with these surgical procedures is minimal, but could include bleeding (these procedures involve so little bleeding that they are often referred to as bloodless surgery ), infection (these procedures involve very small incisions and they are performed in a sterile environment like an operating room where the surgeons wear sterile gowns so infection is rare), and inadvertent injury to surrounding tissues (the possibility of burn injuries when cautery devices are used is significant so I routinely use a high end CO2 laser that has ultrapulse power settings to virtually eliminate burn injuries to allow more thorough surgery with much less risk). (Caption: Operating rooms are designed for surgical procedures requiring anesthesia. The general appearance of an operating room should be clean, bright and uncluttered. Ornamental or decorative items are typically not seen, however, a radio is often heard. Most of the instrument stands are metallic and may be covered with sterile drapes. Nonsterile equipment for the case may be large and is brought into the room as needed.)

19 In vitro fertilization (IVF) is a procedure that generally involves stimulating the maturation of several eggs using injectable fertility drugs, retrieval of these eggs by needle aspiration under ultrasound guidance, fertilization of the retrieved eggs in the laboratory (in vitro) possibly using assisted fertilization techniques such as ICSI, laboratory culture of the fertilized eggs (preimplantation embryos) for several days within an incubator, and transfer of the developing embryos into the woman s uterus. In a high quality IVF center, the clinical pregnancy success rate may be greater than 80% per cycle for highly selected donor egg cycles (in which the egg donors are selected specifically for their likelihood of pregnancy success with IVF) and greater than 60% per cycle for couples with entirely favorable characteristics (younger female with an abundant egg supply and good quality sperm). The cost of at least most of the IVF procedures is sometimes covered by medical insurance, but for uncovered components or when IVF is not a covered service the out of pocket cost can be extremely high. At my office we have several patients with no medical insurance undergoing IVF and I try to help out as much as possible with donated medications and discounted rates for services, but the cost still generally remains high for these couples. Risks of IVF include multiple pregnancies (about 20 25% of pregnancies are twins and less than 3% are triplets), ovarian hyperstimulation syndrome (involving potentially serious fluid shifts within the body), and ovarian torsion (twisting of the ovary, which is very uncommon). These risks are taken very seriously and I limit the number of embryos transferred back to dramatically reduce the risk of higher order multiple pregnancies, monitor egg development very carefully and use the latest techniques to trigger ovulation to reduce the risk of ovarian hyperstimulation syndrome when the risk is elevated, and treat ovarian torsion rapidly to try to minimize the damage to the ovary that is caused by twisting around its vascular pedicles.

20 (Caption: The embryology laboratory (and staff) should be immediately available during the oocyte (egg) retrieval procedure. In this IVF retrieval room setup there is a pocket (slide) door near the foot of the retrieval table that opens up directly into the embryology laboratory. The Reproductive Endocrinologist retrieves ovarian follicular fluid with the eggs at the foot of this table (under ultrasound guidance) and these eggs are immediately passed off to the Embryologists for evaluation and culture.) What options exist if all of the infertility testing and treatments do not successfully result in a pregnancy? If a couple has any concern about the quality or completeness of their fertility treatments at a particular infertility office, I routinely suggest a second opinion at a completely different office. If the couple has been seen at an infertility practice that centers their attention on IVF, then I think it makes best sense to obtain a second opinion at an infertility office that centers their attention on pelvic repair (and visa versa). If the couple has only been treated at an OB GYN office, I suggest a second opinion at an infertility specialist s office whenever available.

21 I rarely suggest that a couple gives up trying to have a baby as long as they have eggs that continue to mature and ovulate, available sperm, and a pelvis that may allow fertilization within the fallopian tube and embryo implantation into the uterine cavity. I have personally had many patients who have become pregnant with simple fertility treatments, after a successful pelvic repair with laparoscopy and hysteroscopy, and with in vitro fertilization. I have also had several patients who have tried at least one cycle of every available fertility treatment and unfortunately did not conceive. With these patients, I strongly suggest that they consider trying less medical treatment rather than more treatment (or continued treatment with what has already not worked). Sometimes a couple will take time off from actively trying to conceive. The couple will stop going to infertility offices regularly and just try to enjoy each other and their lives, develop some fun hobbies, work together on a joint project and remember why they got married in the first place that they love one another. It is always a good idea to live a healthy lifestyle: regular exercise, a healthy diet, and adequate sleep. In many cases, focusing attention on something other than fertility, anything else really, while remaining sexually active will allow a pregnancy to occur naturally. Sometimes a couple will start Yoga for Fertility, Acupuncture for Fertility or herbal treatments. In American Medical Schools, homeopathic treatments are generally not taught, and so I have little expertise in these areas. However, there are several interesting studies that suggest that these techniques or treatments may be effective for fertility care and I have had several patients who have turned to these treatments and thankfully have become pregnant. It is unclear to me whether time away from the stress of medical treatment, the homeopathic remedies, or some other factor is responsible for the improved success but I am always happy when a couple achieves their goals. As long as the homeopathic treatments that are proposed have negligible risk to the couple I think the potential benefits often outweigh the risks for those interested in these types of remedy. For couples that have tried the available medical testing and treatments, and possibly the available natural treatments, without successfully having a baby, I suggest continuing to try on their own for as long as they want throughout their reproductive years while keeping in mind the knowledge that they tried everything in their power to make it work. In several such situations, patients of mine have called me many years later to inform me that their miracle pregnancy finally arrived, just like I told them that it might.

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