{"id":430,"date":"2020-08-13T20:37:21","date_gmt":"2020-08-13T20:37:21","guid":{"rendered":"https:\/\/brooksidepress.org\/basic_obgyn\/?page_id=430"},"modified":"2022-09-08T16:54:26","modified_gmt":"2022-09-08T16:54:26","slug":"infertility","status":"publish","type":"page","link":"https:\/\/brooksidepress.org\/basic_obgyn\/advanced-training\/infertility\/","title":{"rendered":"Infertility"},"content":{"rendered":"<p><iframe loading=\"lazy\" title=\"vimeo-player\" src=\"https:\/\/player.vimeo.com\/video\/169756462\" width=\"640\" height=\"360\" frameborder=\"0\" allowfullscreen=\"allowfullscreen\"><\/iframe><\/p>\n<p>Duration 17:30<\/p>\n<input type='hidden' bg_collapse_expand='69e9dc17298f82007115429' value='69e9dc17298f82007115429'><input type='hidden' id='bg-show-more-text-69e9dc17298f82007115429' value='Show Transcript'><input type='hidden' id='bg-show-less-text-69e9dc17298f82007115429' value='Hide Transcript'><button id='bg-showmore-action-69e9dc17298f82007115429' class='bg-showmore-plg-button bg-blue-button  '   style=\" color:#ffffff;\">Show Transcript<\/button><div id='bg-showmore-hidden-69e9dc17298f82007115429' ><\/p>\n<h2><span style=\"color: #000000\"><strong>Infertility<\/strong><\/span><\/h2>\n<p><strong><u>APGO objectives<\/u><\/strong><\/p>\n<ul>\n<li style=\"list-style-type: none\">\n<ul>\n<li>Define infertility<\/li>\n<li>List the causes of male and female infertility<\/li>\n<li>Describe the evaluation and initial management of an infertile couple<\/li>\n<li>Describe the psychosocial issues associated with infertility<\/li>\n<li>Describe the ethical issues confronted by patients with infertility<\/li>\n<li>Identify the impact of genetic screening and testing on infertility associated treatments<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p><strong><u>Definition<\/u><\/strong><\/p>\n<p>In normally fertile couples, the chance for pregnancy is between 15 and 20% per cycle. 70% of all couples will attain a pregnancy within 6 months, and about 85% within a year.<\/p>\n<p>Infertility is the inability to achieve a pregnancy with regular intercourse and no contraception within one year. For women age 35 or older, infertility begins at six months.<\/p>\n<p>Infertility may be further described as \u201cprimary\u201d or \u201csecondary\u201d<\/p>\n<ul>\n<li style=\"list-style-type: none\">\n<ul>\n<li>Primary Infertility means the patient has never been pregnant.<\/li>\n<li>Secondary infertility means the patient has previously been pregnant, but has been unable to conceive again.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p><strong><u>Causes of male and Female Infertility<\/u><\/strong><\/p>\n<p>Human reproduction requires coordination of several critical factors, including normal motile sperm, ovulation, and an unobstructed passage for the sperm to meet the egg.<\/p>\n<p>Large numbers of sperm must be available at the cervix. They must be able to ascend through the cervix, uterus, and fallopian tubes and subsequently have the capacity to fertilize the egg.\u00a0 Reduced numbers of functionally normal sperm is considered a \u201cmale factor,\u201d and contributes to infertility in 30-40% of couples.<\/p>\n<p>There are a variety of causes of male factor infertility.<\/p>\n<p><strong>Hypothalamic-Pituitary Disorders.<\/strong><\/p>\n<p>Normal spermatogenesis requires normal pituitary FSH and LH release.<\/p>\n<p>Any disorder, which disrupts these signals, may lead to low sperm counts. Fewer than 15 million sperm per cc is considered low.<\/p>\n<p>Hypothalamic Pituitary disorders that may cause low sperm counts include Idiopathic gonadotropin deficiency, Kallmann Syndrome (or congenital GnRH deficiency), Hypothalamic or Pituitary tumors, Chronic systemic illnesses, Hyperprolactinemia, certain Pharmacologic agents (Androgens, Estrogens, Glucocorticoids), and Obesity.<em>\u00a0<\/em><\/p>\n<p>The absence or destruction of functional testicular tissue may also cause male factor infertility.<\/p>\n<p>Examples of such conditions include Klinefelter Syndrome (46XXY), Y chromosome microdeletions, Cryptorchidism, Pharmacologic agents (specifically chemotherapeutic agents), environmental toxins (such as smoking), infections (viral orchitis) and chronic systemic illnesses.<\/p>\n<p>Finally, an unobstructed pathway from the epididymis to the urethral meatus is required for sperm to be emitted during intercourse.<\/p>\n<p>Obstructions may be caused by epididymal cysts, congenital bilateral absence of the vas deferens, and infections such as gonorrhea and Chlamydia, which can cause scarring of the vas deference.<\/p>\n<p>Erectile or ejaculatory problems such as spinal cord disease, retrograde ejaculation, or erectile dysfunction may cause male factor infertility, as can Kartagener syndrome (or primary ciliary dyskinesia).<\/p>\n<p>For pregnancy to occur, sexual intercourse must take place shortly before or with ovulation. This timing is important because while normal sperm can remain functional inside the woman\u2019s body for up to several days, the egg is only viable for fertilization for 12-24 hours after ovulation.<\/p>\n<p><strong>Ovulation Disorders<\/strong><\/p>\n<p>Ovulation problems are found in 20-40% of all infertile couples. \u00a0Problems may occur anywhere along the hypothalamic-pituitary-ovarian axis.<\/p>\n<p><strong><em>Hypothalamic Pituitary Disorders<\/em><\/strong><\/p>\n<p>Any condition interfering with the pituitary signals of FSH or LH, which are necessary for normal follicular recruitment and maturation, can lead to ovulation failure.<\/p>\n<p>Examples include Idiopathic gonadotropin deficiency, Kallmann Syndrome (or congenital GnRH deficiency), Hypothalamic or Pituitary tumors, Chronic systemic illnesses, Hyperprolactinemia, Thyroid dysfunction, Pharmacologic agents (Androgens, Estrogens, Glucocorticoids), and Obesity.<\/p>\n<p><strong><em>Primary Ovarian disorders<\/em><\/strong><\/p>\n<p>Abnormally functioning ovarian tissue may also cause anovulation.<\/p>\n<p>One example is premature ovarian insufficiency. This insufficiency may be linked to ovarian dysgenesis, prior use of chemotherapy, pelvic radiation therapy, or may be from a genetic predisposition.<\/p>\n<p>Another leading cause of anovulatory infertility is polycystic ovary syndrome (or PCOS).\u00a0 Although often considered a disorder of the ovary, this disease is the result of a complex pathophysiology involving the hypothalamus, pituitary, and ovary.<\/p>\n<p><strong>Passageway<\/strong><\/p>\n<p>Sperm need an unobstructed passage to meet the mature egg, as well as an optimal environment for the pregnancy to implant and grow.<\/p>\n<p>This requires that the cervix is patent, the fallopian tubes are open and functional, and a normal uterine cavity, with a\u00a0 receptive endometrium, is present. While cervical and uterine factors are infrequent causes of infertility, tubal and peritoneal pathology comprise 30-40% of all causes of infertility.<\/p>\n<p><strong><em>Cervical Factors<\/em><\/strong><\/p>\n<p>Cervical mucous functions as a healthy reservoir for sperm.<\/p>\n<p>If the cervical glands are reduced in number due to previous cervical excision procedures (such as cone biopsies, or LEEP procedures) this may lead to reduced cervical mucous.\u00a0 Cervical procedures may also cause scarring and cervical stenosis.<\/p>\n<p><strong><em>Uterine Factors<\/em><\/strong><\/p>\n<p>Fibroids may contribute to a uterine factor if they have a submucous component or distort the uterine cavity, as can endometrial polyps.<\/p>\n<p>Uterine scarring (Asherman\u2019s syndrome) or the absence of a uterus altogether (also known as Mayer-Rokitansky-Juster-Hauser syndrome) may cause uterine factor infertility.<\/p>\n<p><strong><em>Tubal and Peritoneal Pathology<\/em><\/strong><\/p>\n<p>Tubal and Peritoneal pathology together comprise a large proportion of the most common etiologies of infertility.<\/p>\n<p>Pelvic inflammatory disease, tubo-ovarian abcess, and prior gonorrhea or chlamydia infections may cause long-term structural changes which ultimately compromise tubal integrity and function.<\/p>\n<p>These abnormalities may not only lead to infertility, but may also increase the risk for ectopic pregnancy.\u00a0 Conversely, a history of ectopic pregnancy should be a red flag to the practitioner for the possibility of underlying tubal disease, especially if tubal surgery (like a salpingostomy) is performed.<\/p>\n<p>Endometriosis is a condition in which ectopic endometrial tissue is found on the peritoneum, ovary, tube, and sometimes in extrapelvic organs, and has a strong association with infertility.<\/p>\n<p>With severe endometriosis, inflammation and scar tissue are considered major contributors to infertility. But with lesser degrees of endometriosis, it may be unclear whether the endometriosis is the cause for infertility, or rather represent an effect of some other factor that causes both the endometriosis and the infertility. Endometriosis is present in between 9 and 50% of infertile women.<\/p>\n<p><strong><em>Unexplained Infertility<\/em><\/strong><\/p>\n<p>In approximately 10-15% of all couples, there is no identifiable reason for infertility; these couples are considered to have unexplained infertility.\u00a0 This doesn\u2019t mean there is no cause. Rather, it means that whatever is causing the infertility is not yet detectable with our proven methods.<\/p>\n<p>Some unexplained infertility relates to natural reproductive ageing, and the likely underlying etiologies relate to anomalies in gametes or implantation, for which there are no recognized validated tests.<\/p>\n<p><strong><u>Evaluation<\/u><\/strong><\/p>\n<p>The evaluation of an infertile couple should begin with a history and physical examination.<\/p>\n<p>This includes the duration of infertility, the results of any prior testing or treatment, and the couple\u2019s sexual history, particularly coital frequency.<\/p>\n<p>For the female, inquiry is made about her obstetrical history (if any), gynecologic history, and menstrual history. Significant historical issues would include Galactorrhea, Hirsutism, Dyspareunia or Pelvic Pain<\/p>\n<p>Noted are prior contraceptive use, any history of surgical procedures in the genital area or abdomen, and any STD history.<\/p>\n<p>In addition to inquiring about any chronic medical illnesses or surgical history, family history is important. Evidence may be found for premature ovarian insufficiency, recurrent pregnancy loss, infertility, or other inheritable disorders.<\/p>\n<p>It is important to also ask about the couples\u2019 ethnic background in order to offer the most targeted preconception genetic screening tests<\/p>\n<p>A Social History is obtained, to include an assessment of occupational exposures, use of alcohol, tobacco, or recreational drugs.<\/p>\n<p>Current medications and allergies are noted.<\/p>\n<p>Her physical exam will include height, weight, signs of androgen excess, examination of the thyroid, breasts, and a pelvic exam.<\/p>\n<p>The male partner is generally referred to a urologist, or family physician with special skills in evaluating and treating male infertility.<\/p>\n<p><strong>Testing<\/strong><\/p>\n<p>The laboratory evaluation of the infertile couple involves an assessment of (1) Ovarian reserve (2) Tubal Patency (3) Assessment of ovulatory and Endocrine function and (4) Male factor (through a semen analysis)<\/p>\n<p><strong><em>Ovarian Reserve Testing<\/em><\/strong><\/p>\n<p>The most dynamic component of infertility testing is the assessment of ovarian reserve.\u00a0 Ovarian reserve testing aims to determine the functional capacity of a woman\u2019s remaining eggs.\u00a0 It is important to remember that these tests do not tell whether a woman can or cannot get pregnant, they simply offer a guide for the practitioner in determining the likelihood of success with fertility treatment.<\/p>\n<p>In general there are 3 validated tests for ovarian reserve.<\/p>\n<p>The first day of a menstrual flow is day 1. On Day 3, blood tests are obtained, including an FSH, an estradiol, and an ultrasound scan for antral follicle count. An FSH level &gt;10-20 IU\/mL is considered abnormally high, suggesting the ovary is not responding normally. This is related to a poor chance for success with fertility treatment.\u00a0 Transvaginal ultrasound is used to determine the number of antral follicles; low numbers of follicles correlates with poor ovarian reserve.<\/p>\n<p>An elevated estradiol level (&gt;60-80pgmL) in the presence of a normal FSH level is also associated with a poor prognosis for fertility treatments. Women with poor ovarian reserve tend to demonstrate premature follicle recruitment, which results in an abnormally high estradiol.<\/p>\n<p>The cycle independent test for ovarian reserve is Antimullerian Hormone level (AMH).\u00a0 AMH levels reflects the availability of primordial follicles, declines with advancing maternal age, and is absent at menopause. Age-adjusted normal values are used to evaluate the reproductive potential for infertile women.<\/p>\n<p><em>Assessing Tubal Patency<\/em><\/p>\n<p>There are several ways to assess tubal patency.<\/p>\n<p>Hysterosalpingogram (HSG) utilizes real time fluoroscopy to image the passage of radio-opaque dye, injected through the uterus and out of the fallopian tubes.<\/p>\n<p>Abnormal tubal morphology and the absence of free spill in to the peritoneal cavity can be helpful surrogate makers for the presence of extra-tubal pelvic adhesive disease.<\/p>\n<p>More recently, Sono-hysterosalpingography with saline instillation has become a popular replacement for HSG.\u00a0 This technique utilizes Doppler flow to visualize the tubes as they fill with saline; the presence of fluid in the cul de sac confirms patency of at least one fallopian tube.\u00a0 If either of these tests are abnormal or indeterminate, the gold standard assessment of tubal patency is chromotubation at the time of laparoscopy.<\/p>\n<p><strong>Assessment of ovulatory function and Endocrine evaluation<\/strong><\/p>\n<p>The single best predictor that a woman is ovulating regularly is the presence of regular menstrual cycles every 21 to 35 days.\u00a0 However, lab and imaging studies can also be done to confirm this.<\/p>\n<p>In a woman with typical 28-30 day cycles, serum progesterone values on cycle days 21-24 should be elevated (&gt;3 ng\/dL), reflecting ovulation.<\/p>\n<p>Progressive follicular growth and then collapse with ovulation can be visualized with serial transvaginal ultrasounds, confirming development and release of an egg.<\/p>\n<p>Women with a history suggesting ovulatory dysfunction should undergo a thorough endocrine evaluation.\u00a0 This includes serum TSH, FT4 and fasting prolactin levels, and targeted evaluation of male hormone levels in those women with complaints or signs of androgen excess.<\/p>\n<p><strong>Male Factor (Semen analysis)<\/strong><\/p>\n<p>The final component of the infertility evaluation is the semen analysis.<\/p>\n<p>The male partner should provide a specimen after 2-5 days of abstinence.\u00a0 The specimen is evaluated based on several criteria: volume, concentration, motility, and morphology.\u00a0 Abnormalities in any one of these parameters may warrant additional evaluation by a urologist.<\/p>\n<p>For instance, if no sperm is visualized (azoospermia), this may suggest gonadal failure (if normal volume ejaculate is present) or obstruction (if low volume ejaculate is present).\u00a0 In the former, a serum FSH, E2, Testosterone and prolactin level should be obtained.\u00a0 In the latter, a thorough physical exam should be performed by a urologist.<\/p>\n<p><strong>Preconception Counseling<\/strong><\/p>\n<p>Another important component of the initial evaluation is centered on preconception counseling.<\/p>\n<p>Here, we have a unique opportunity to ensure adequate testing and preconception treatment to lower antenatal risks.\u00a0 All pre-existing medical conditions should be assessed and optimized prior to pregnancy.\u00a0 Titers for rubella and varicella should be obtained to determine ongoing immunity.<\/p>\n<p>Finally, preconception genetic screening should be offered.\u00a0 This screening can include an assessment of carrier status for cystic fibrosis, spinal muscular atrophy, thalassemia, and sickle cell disease, amongst others.<\/p>\n<p><strong><u>Management<\/u><\/strong><\/p>\n<p>In some cases, infertility is a result of a single major problem that is preventing pregnancy. In other cases, there are a number of minor factors, none of which will completely prevent pregnancy, but collectively may prolong the time to pregnancy.<\/p>\n<p>The choice for fertility treatment is dependent on the couples\u2019 initial evaluation.\u00a0 Targeted treatment is best for isolated abnormalities, such as anovulation or azoospermia.\u00a0 However, when more than one abnormality exists, or the evaluation is normal, a more empiric approach should be considered.\u00a0 Consultation with a reproductive endocrinologist and infertility specialist is critical to determine the best treatment approach for couples with infertility.<\/p>\n<p><strong><u>Psychosocial issues associated with infertility<\/u><\/strong><\/p>\n<p>Numerous studies have shown increased symptoms of stress and anxiety in infertile women compared to the general population; not only is the diagnosis stressful, but chronic stress itself may reduce the success of fertility treatment (although the mechanism for this is poorly understood).<\/p>\n<p>There are reasons for increased stress&#8211;the diagnosis of infertility can impact the couples\u2019 relationship, their relationship with family and friends, their financial well-being, and potentially their outlook on life.\u00a0 Ultimately, both diagnosis and treatment requires not only a physical commitment from the couple, but an emotional and financial commitment as well.<\/p>\n<p>As the infertile couple is vulnerable to psychosocial issues, it is important for the practitioner to recognize signs of stress, depression, and anxiety.\u00a0 Professional counseling, through a psychiatrist, psychologist, social worker, marriage or family therapist can be very helpful, and sometimes relationship or life-saving.\u00a0 Consider referral for counseling if a patient or her partner experience any of the following:<\/p>\n<ul>\n<li style=\"list-style-type: none\">\n<ul>\n<li>Persistent feelings of sadness, guilt, or worthlessness<\/li>\n<li>Social isolation<\/li>\n<li>Loss of interest in usual activities and relationships<\/li>\n<li>Depression<\/li>\n<li>Agitation and or anxiety<\/li>\n<li>Mood swings<\/li>\n<li>Constant preoccupation with infertility<\/li>\n<li>Marital problems<\/li>\n<li>Difficulty with \u201cscheduled\u201d intercourse<\/li>\n<li>Difficulty concentrating or remembering<\/li>\n<li>Increased use of alcohol or drugs<\/li>\n<li>Changes in appetite, weight, or sleep patterns<\/li>\n<li>Thoughts about Suicide or Death<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>The ASRM patient website (ReproductiveFacts.org) provides several resources addressing the concerns of couples who have been given a diagnosis of infertility or who choose to pursue treatment. \u00a0Links to support groups and other national organizations, including Resolve (ww.resolve.org), American Fertility association (TheAFA.org), and the InterNational Counsil on infertility information dissemination, Inc (inciid.org), are also provided.<\/p>\n<p><strong><u>Ethical Issues in Reproductive Medicine<\/u><\/strong><\/p>\n<p>As the field of reproductive medicine evolves, so does the ethics of practice.<\/p>\n<p>As humans, we value the right to reproduce, to build a family, and to take care of that family.\u00a0 As practitioners, we have an obligation to understand the risks, benefits, and indications of treatment, and also the impact of treatment (or of no treatment) on the individual, the couple, and to society\u2014 we must use the available technologies in the most conscientious way.<\/p>\n<p>The American Society of Reproductive Medicine provides guidance for tackling some of the most common ethical issues in practice.\u00a0 Examples include:<\/p>\n<ul>\n<li style=\"list-style-type: none\">\n<ul>\n<li>Child rearing ability and the provision of fertility services<\/li>\n<li>Embryo donation<\/li>\n<li>Disparities in access to care<\/li>\n<li>Disposition of abandoned embryos<\/li>\n<li>Fertility treatment when the prognosis is poor or futile<\/li>\n<li>Oocyte or embryo donation in women of advanced age<\/li>\n<li>Financial compensation of oocyte donation<\/li>\n<li>Use of pre-implantation genetic diagnosis, and<\/li>\n<li>The use of family members as gamete donors and surrogates.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>To help address these issues, infertility centers may collaborate with legal counsel, and draft office policies and procedures. It is important to ensure open dialogues with patients from the beginning of treatment to help in developing accurate expectations.<\/p>\n<p><strong><u>Impact of genetic screening and testing associated with infertility treatments<\/u><\/strong><\/p>\n<p>One of the most significant breakthroughs in reproductive medicine has been the evolution and usage of preimplantation genetic screening (PGS) and genetic diagnosis (PGD).<\/p>\n<p>Preimplantation genetic screening refers to the testing for aneuploidy, or copy number variations of the autologous and sex chromosomes.<\/p>\n<p>Preimplantation genetic diagnosis refers to testing for specific single gene disorders, if the parents are known carriers. Examples include Cystic Fibrosis, Spinal Muscular Atrophy, Thalassemia, Fragile X Syndrome, Sickle Cell anemia, Hereditary Breast\/Ovarian cancer (BRCA1 and BRCA2).<\/p>\n<p>The process of preimplantation genetic screening first requires the couple to undergo in vitro fertilization (IVF).\u00a0 The female partner will take injections to stimulate follicle development, and then she subsequently undergoes an ultrasound guided oocyte retrieval.<\/p>\n<p>After retrieval, the cohort of mature eggs are selected and injected with the male partner\u2019s sperm through a process called intracytoplasmic sperm injection (ICSI).<\/p>\n<p>While a number of embryo biopsy strategies have been used with varying degrees of success, most centers have moved towards genetic analysis at the blastocyst stage.<\/p>\n<p>At this stage, the embryo contains hundreds of cells, which have further divided into what will ultimately become the fetus (inner cell mass) and the placenta (trophectoderm).\u00a0 Several cells from the trophectoderm are biopsied and subjected to genetic analysis, which may include comparative genomic hybridization or next generation sequencing.<\/p>\n<p>Although effective and reasonably safe, there are drawbacks to blastocyst biopsy. One is the possibility of placental mosaicism, which can reduce accuracy.<\/p>\n<p>To counteract this risk, patients are still advised to undergo routine noninvasive prenatal screening during pregnancy (in cases of PGS) and consider invasive prenatal screening (in cases of PGD).<\/p>\n<p>Another drawback to blastocyst biopsy is the possibility of having no embryos survive to the blastocyst stage in vitro, which means there would be no embryos to biopsy.<\/p>\n<p>To counteract this risk, couples often \u201cbatch\u201d their IVF cycles, meaning they undergo several cycles of IVF back-to-back to increase the pool of embryos available for analysis, especially if the female partner has decreased ovarian reserve.<\/p>\n<p>Ultimately the current literature suggests that the chance of live birth after the transfer of a euploid embryo, regardless of the age of the recipient, is approximately 65%.<\/p>\n<p>The implications and usage of PGD are clear:\u00a0 couples can elect to reduce their risk of having a child with a disease that causes significant morbidity or mortality, if they themselves are carriers.<\/p>\n<p>The indications for PGS however are still evolving.<\/p>\n<p>Patient populations described to potentially benefit from this technology include couples in whom the female partner is of advanced maternal age, couples with a history of recurrent pregnancy loss or recurrent implantation failure following previous IVF cycles, and women with uterine anomalies or prior poor antenatal outcomes who require the lowest risk for multiple gestation.<\/p>\n<p><em><u>\u00a0<strong>Resources<\/strong><\/u><\/em><\/p>\n<p><em>Practice Committee of the American Society for Reproductive Medicine.\u00a0 Definitions of infertility and recurrent pregnancy loss: a committee opinion.\u00a0 Fertility and Sterility 2013; 99:63<\/em><\/p>\n<p><em>Practice Committee of the American Society for Reproductive Medicine.\u00a0 Diagnostic evaluation of the infertile male: a committee opinion.\u00a0 Fertility and Sterility 2015; 103:e18-25<\/em><\/p>\n<p><em>Practice Committee of the American Society for Reproductive Medicine.\u00a0 Diagnostic evaluation of the infertile female: a committee opinion.\u00a0 Fertility and Sterility 2015; 103:e44-50<\/em><\/p>\n<p><em>Practice Committee of the American Society for Reproductive Medicine.\u00a0 Female Age Related fertility decline.\u00a0 Fertility and Sterility 2014; 101:633-4<\/em><\/p>\n<p><em>American Society for Reproductive Medicine.\u00a0 Infertility Counseling and Support: When and Where to Find it.\u00a0 Fact Sheet.\u00a0 <\/em><a href=\"http:\/\/www.reproductivefacts.org\"><em>www.reproductivefacts.org<\/em><\/a><\/p>\n<p><em>Ethics Committee of the American Society for Reproductive Medicine.\u00a0 American Society for Reproductive Medicine.\u00a0 (2011-2016) <\/em><a href=\"http:\/\/www.asrm.org\/Ethics\/Reports\"><em>www.asrm.org\/Ethics\/Reports<\/em><\/a><\/p>\n<p><em>Bayer, S. R., Alper, M.M., &amp; Penzias, A.S. (2002).\u00a0 The Boston IVF handbook of infertility: A practical guide for practitioners who care for infertile couples.\u00a0 Boca Raton, FL: Parthenon.\u00a0 <\/em><\/p>\n<p>Dr. Nayak<\/p>\n<p><\/div>\n<hr \/>\n<p><iframe loading=\"lazy\" src=\"https:\/\/www.youtube.com\/embed\/attcQgvt5Iw\" width=\"560\" height=\"315\" frameborder=\"0\" allowfullscreen=\"allowfullscreen\"><\/iframe><\/p>\n<p>Duration 9:34<\/p>\n<input type='hidden' bg_collapse_expand='69e9dc172a1517024333808' value='69e9dc172a1517024333808'><input type='hidden' id='bg-show-more-text-69e9dc172a1517024333808' value='Show Teaching Transcript'><input type='hidden' id='bg-show-less-text-69e9dc172a1517024333808' value='Hide Teaching Transcript'><button id='bg-showmore-action-69e9dc172a1517024333808' class='bg-showmore-plg-button bg-blue-button  '   style=\" color:#ffffff;\">Show Teaching Transcript<\/button><div id='bg-showmore-hidden-69e9dc172a1517024333808' ><\/p>\n<p class=\"p2\">Mullerian Anomalies<\/p>\n<p class=\"p3\">Jehnsen J, Liang A<\/p>\n<p class=\"p4\"><b>Clinical cases applicability: <\/b>Mullerian anomalies, primary amenorrhea, recurrent pregnancy loss<\/p>\n<p class=\"p4\"><b>Learning objectives: <\/b><\/p>\n<p class=\"p5\">1) Describe the embryologic origins of the reproductive tract<\/p>\n<p class=\"p5\">2) Identify genes and hormones involved in sexual differentiation<\/p>\n<p class=\"p4\">3) Understand the mechanisms of how Mullerian anomalies form<\/p>\n<p class=\"p4\"><b>What are the embryologic origins of the reproductive system? <\/b><\/p>\n<p class=\"p4\">Mesoderm <span class=\"s2\">\uf0e0 <\/span>Urogenital ridge<\/p>\n<p class=\"p4\">1) Genital ridge <span class=\"s2\">\uf0e0 <\/span>undifferentiated gonad <span class=\"s2\">\uf0e0 <\/span>ovary\/testis<\/p>\n<p class=\"p4\">2) Nephrogenic cord <span class=\"s2\">\uf0e0 <\/span>kidneys<\/p>\n<p class=\"p4\">3) Paramesonephric (Mullerian) ducts <span class=\"s2\">\uf0e0 <\/span>fallopian tubes, uterus, upper vagina<\/p>\n<p class=\"p4\">4) Mesonephric (Wolffian) ducts <span class=\"s2\">\uf0e0 <\/span>ureters, male genital ducts, seminal vesicles<\/p>\n<p class=\"p4\"><b>How does sexual differentiation occur (see figure 1)? <\/b><\/p>\n<p class=\"p4\"><b>SRY gene <\/b>(Sex-determining Region of the Y chromosome) in the short arm of Y chromosome <span class=\"s2\">\uf0e0 <\/span>encodes for SRY protein (previously known as testis-determining factor &#8211; TDF)<\/p>\n<p class=\"p4\">SRY protein <span class=\"s2\">\uf0e0 <\/span>chain of events leading to gonad differentiation into testes and production of <b>anti-mullerian hormone <\/b>and <b>testosterone <\/b><\/p>\n<p class=\"p4\"><b>What are key hormones in fetal male development (see figure 1)? <\/b><\/p>\n<p class=\"p7\">&#8211; Testosterone <span class=\"s3\">\uf0e0 <\/span>persistence and differentiation of wolffian (mesonephric) duct<b>s <\/b><\/p>\n<p class=\"p4\">&#8211; Anti-mullerian hormone (produced by Sertoli cells)<span class=\"s3\">\uf0e0 <\/span>regression of mullerian ducts<\/p>\n<p class=\"p4\"><b>What are conditions required for normal fetal female development (see figure 1)? <\/b><\/p>\n<p class=\"p8\">&#8211; Considered the \u201cdefault\u201d<\/p>\n<p class=\"p4\">&#8211; Absence of SRY, testosterone &amp; Anti-mullerian hormone <span class=\"s3\">\uf0e0 <\/span>regression of wolffian ducts and persistence of <b>mullerian (paramesonephric) ducts <\/b><\/p>\n<p class=\"p4\"><b>What causes mullerian anomalies (see figure 2)? <\/b>Affects 2-4% in women with normal reproductive outcomes, 5-25% for women with adverse reproductive outcomes; NORMAL ovarian function with normal secondary sex characteristics<\/p>\n<p class=\"p9\"><span class=\"s4\">1) Errors in <b>organogenesis <\/b>\u2013 Mullerian agenesis (\u201cMRKH\u201d <\/span>Mayer Rokitansky K\u00fcster Hauser), all or part of the mullerian tract fails to form or is underdeveloped: absent vagina, variable uterine development<\/p>\n<p class=\"p4\">2) Errors in <b>fusion <\/b><\/p>\n<p class=\"p10\">a. Uterine didelphys \u2013 \u201cdouble uterus\u201d, two mullerian ducts fail to fuse, duplication of the reproductive structures<\/p>\n<p class=\"p10\">b. Bicornuate uterus \u2013 Fundus is indented, partial fusion of the mullerian ducts<\/p>\n<p class=\"p4\">c. Unicornuate uterus \u2013 asymmetric lateral fusion defect \u2013 one cavity usually normal, while other duct poorly developed (+\/- rudimentary horn)<\/p>\n<p class=\"p4\">3) Errors in <b>septal resorption <\/b><\/p>\n<p class=\"p5\">a. Septate uterus (complete or partial) \u2013 Normal external surface of the fundus (compared to bicornuate), incomplete resorption of the midline septum between the 2 mullerian ducts<\/p>\n<p class=\"p4\">b. Arcuate uterus \u2013 slight midline septum with minimal, and often broad, fundal cavity indentation<\/p>\n<p class=\"p4\"><b>Why are mullerian anomalies associated renal anomalies? What is the incidence? <\/b><\/p>\n<p class=\"p5\">&#8211; Paramesonephric system develops with the renal system (both originate from the urogenital ridge)<\/p>\n<p class=\"p4\">&#8211; Renal anomalies are found in 20-30% of women with mullerian defects<\/p>\n<p class=\"p2\">Mullerian Anomalies<\/p>\n<p class=\"p3\">Jehnsen J, Liang A<\/p>\n<p class=\"p4\"><b>Figure 1 <\/b><\/p>\n<p class=\"p4\"><b>Figure 2 <\/b><\/p>\n<p class=\"p4\">References:<\/p>\n<p class=\"p5\">&#8211; Beckmann, Charles R. B. (Eds.) (2010) <i>Obstetrics and gynecology.<\/i>Baltimore, MD : Wolters Kluwer Health\/Lippincott Williams &amp; Wilkins<\/p>\n<p class=\"p5\">&#8211; DeCherney AH, Nathan L, Laufer N, Roman AS. <i>CURRENT Diagnosis &amp; Treatment: Obstetrics &amp; Gynecology, 11e<\/i>; 2013<\/p>\n<p class=\"p5\">&#8211; Renu D, Rao B G, Ranganath K, Namitha. Persistent mullerian duct syndrome. Indian J Radiol Imaging 2010;20:72-4<\/p>\n<p class=\"p4\">&#8211; Iverson RE, DeCherney, AH, Laufer, MR. Clinical manifestations and diagnosis of congenital anomalies of the uterus. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (2017)<\/p>\n<p><\/div>\n<hr \/>\n<p><iframe loading=\"lazy\" src=\"https:\/\/www.youtube.com\/embed\/auoVVD0Vgow\" width=\"560\" height=\"315\" frameborder=\"0\" allowfullscreen=\"allowfullscreen\"><\/iframe><\/p>\n<p>Duration 2:15<\/p>\n<input type='hidden' bg_collapse_expand='69e9dc172a5001052021788' value='69e9dc172a5001052021788'><input type='hidden' id='bg-show-more-text-69e9dc172a5001052021788' value='Show Transcript'><input type='hidden' id='bg-show-less-text-69e9dc172a5001052021788' value='Hide Transcript'><button id='bg-showmore-action-69e9dc172a5001052021788' class='bg-showmore-plg-button bg-blue-button  '   style=\" color:#faf7f7;\">Show Transcript<\/button><div id='bg-showmore-hidden-69e9dc172a5001052021788' ><\/p>\n<p>00:03<br \/>\nwe&#8217;ve been trying for about a year and<br \/>\n00:05<br \/>\nfriends dripped throughout that year it<br \/>\n00:07<br \/>\nstarts to get pregnant and and I think<br \/>\n00:09<br \/>\nthen a shadow of doubt started to creep<br \/>\n00:11<br \/>\nin for both of us for both myself and my<br \/>\n00:13<br \/>\nhusband we started to wonder you know<br \/>\n00:15<br \/>\nshould something have happened for us it<br \/>\n00:17<br \/>\nwasn&#8217;t so much a shock it was gradual it<br \/>\n00:20<br \/>\nhappened you know every month my period<br \/>\n00:22<br \/>\nrotella I&#8217;d be here two days before it<br \/>\n00:23<br \/>\nwas gob feeling his dragging pains in my<br \/>\n00:25<br \/>\nstomach I just thought there would be<br \/>\n00:27<br \/>\nsomething simple and straightforward<br \/>\n00:28<br \/>\nthat we&#8217;d overlooked and there wasn&#8217;t<br \/>\n00:31<br \/>\nand and they said we needed to see a<br \/>\n00:33<br \/>\nspecialist which was very very scary and<br \/>\n00:35<br \/>\nI remember at that point I think this<br \/>\n00:38<br \/>\nwas the first of my burst into tears and<br \/>\n00:40<br \/>\ndoctors and waiting rooms the first of<br \/>\n00:42<br \/>\nmany I have to say I think the shock of<br \/>\n00:44<br \/>\nit and also it felt very serious all of<br \/>\n00:47<br \/>\na sudden and if we were seeing a<br \/>\n00:49<br \/>\nspecialist a fertility specialist then<br \/>\n00:51<br \/>\nthere was a problem with our fertility<br \/>\n00:53<br \/>\ncomplete kicking the team&#8217;s I think you<br \/>\n00:56<br \/>\nknow it said before it&#8217;s you&#8217;re born<br \/>\n00:58<br \/>\ninto thinking you know you&#8217;re in here on<br \/>\n01:00<br \/>\nthis earth to do what you&#8217;re doing you<br \/>\n01:02<br \/>\nyou have children and you pass on your<br \/>\n01:04<br \/>\nname you pass on your bloodline and all<br \/>\n01:08<br \/>\nthat rubbish really but exist because<br \/>\n01:10<br \/>\nit&#8217;s not have assist you but it might<br \/>\n01:12<br \/>\nnot happen because I think that&#8217;s the<br \/>\n01:14<br \/>\none of the most difficult things about<br \/>\n01:16<br \/>\nit really you do feel that you are not<br \/>\n01:18<br \/>\nthe same as everyone else that you&#8217;ve<br \/>\n01:19<br \/>\nkind of failed as a woman somehow<br \/>\n01:22<br \/>\neveryone else seems to be able to do<br \/>\n01:23<br \/>\nthis thing so easily and you just grow<br \/>\n01:25<br \/>\nup expecting that you&#8217;ll be able to have<br \/>\n01:27<br \/>\nchildren if you want to and discovering<br \/>\n01:30<br \/>\nthat you can&#8217;t it&#8217;s really hard to<br \/>\n01:33<br \/>\ndescribe how much that affects you<br \/>\n01:35<br \/>\nactually how much it affects the way you<br \/>\n01:36<br \/>\nsee yourself and how you feel about<br \/>\n01:38<br \/>\nyourself and I realized as I sort of<br \/>\n01:42<br \/>\nwent into it I had no idea what it<br \/>\n01:44<br \/>\nentailed at all and I think I think it&#8217;s<br \/>\n01:48<br \/>\nthis thing that&#8217;s kind of thrown around<br \/>\n01:50<br \/>\nand people always just as soon as a as<br \/>\n01:52<br \/>\nan option and first of all they assume<br \/>\n01:55<br \/>\nthat without any real understanding of<br \/>\n01:57<br \/>\nhow often it doesn&#8217;t work you know for<br \/>\n02:00<br \/>\none thing and just the physical and<br \/>\n02:03<br \/>\nemotional toll it takes on you<br \/>\n02:06<br \/>\nyou<\/p>\n<p><\/div>\n<hr \/>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Duration 17:30 Duration 9:34 Duration 2:15 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