قراءة
عرض

Dr.Sumeya

Obgectives
This lecture explain the definition ,types, causes, investigations and lines of treatments for both male and female infertility

Background

Definition:Infertility = “failure to conceive following 1 year of unprotected intercourse if under 35 years of age or six months if over 35”.10-15% couples affectedEtiologyCouples:16% Tubal and pelvic pathology21 % Male problems29% Ovulatory dysfunction18% Unexplaine7% Endometriosis,2%Cervical,3%Uterine,4%Multiple

For a woman with a normal menstrual cycle of 28 days, ovulation occurs around day 14. The average survival time of the oocyte is around 24 hours, while after ejaculation sperm may survive for up to 7 days in the female reproductive tract.

Background

Normal couple: 25-30% chance of pregnancy per ovulatory cycle Primary -Couple has never conceived Secondary - couple has had at least one prior conception

Infertility

Time of Exposure % Pregnant 3 months 60% 6 months 70% 1 year 85% 18 months 90%

Approach to Infertility

Causes Male Female Combined Unexplained

Male Infertility

Anatomy of the testis

Hypothalamic-Pituitary-Gonadal Axis

Male Infertility
HypothalamusCongenital abnormalities of hypothalamuse.g. Kallman’s syndromeStarvation, stress or severe illnessTumors (craniopharyngioma, metastatic tumor)Head injuryInflammation (sarcoidosis)Infection (tuberculosis)XRTDrugs: marijuana,

Male Infertility

Pituitary Endocrine: thyroid, prolactin Tumors Inflammation: sarcoidosis, meningitis Infiltration Infarction Trauma/XRT Drugs: anabolic steroids

Male Infertility

Testis: Congenital: Klinefelters (XXY), developmental disorders Disorders of gonadal steroidgenesis Infection: chlamydia, prostatitis, mumps orchitis Autoimmune Cryptorchidism Tumors; chemo/XRT Drugs / alcohol Vascular: testicular torsion

Male Infertility

Temperature Rise in scrotal temperature Occupation Varicocoele

Male Infertility

Post testicular causes: Impotence/EjaculationA-Neurogenic: medications (α-blockers, methyldopa)B-Endocrine: diabetesCongenital: absence vas deferens (CF)Genetic: cystic fibrosisPrimary ciliary dyskinesia: Kartagener syndromeHypospadiaVasectomy

Male Infertility

Investigations: semen analysis Abstain 2-7 days prior At least 2 samples over different period of time If abnormal: Blood work: FSH, LH, TSH, testosterone, PRL Testicular U/S Chromosomal analysis

Semen

also known as seminal fluid, is an organic fluid that may contain spermatozoa. It is secreted by the gonads ( testis and accessory sex glans). Seminal fluid contains several components besides spermatozoa: proteolytic and other enzymes as well as fructose are elements of seminal fluid which promote the survival of spermatozoa, and provide a medium through which they can move or "swim".

Male Infertility

. Semen viscosity: Normal semen has a viscous texture. Increase in viscosity may occur due to hypofunction of seminal vesicles. High viscosity may affect sperm motility and concentration. Increase in viscosity may reduce the success of intrauterine insemination (IUI) and in vitro fertilization (IVF) . . Appearance of the ejaculate: A normal ejaculate has a homogenous grey-opalescent appearance.A whitish colour may indicate high sperm numbers or presence of leukocytes a yellowish appearance and purulent smell indicate infections. A reddish-brown colour indicates the presence of red blood cells (hemospermia) .


Semen volume: The lower reference limit for semen volume is 1.5 ml (WHO 2010). A small volume may also be due to loss of part of the specimen, retrograde ejaculation, abnormality or infection of accessory sex glands, or ejaculatory duct obstruction. An extremely high volume may indicate inflammation or urine contamination and is associated with lower conception rates . Semen pH: The pH of semen reflects the balance between the pH values of the different accessory gland secretions, mainly the alkaline seminal vesicular secretion and the acidic prostatic secretion. A lower threshold value is 7.2

Microscopic characteristics

Agglutination Agglutination of spermatozoa means that motile spermatozoa stick to each other, head to head, midpiece to midpiece, tail to tail, or mixed, e.g. midpiece to tail. The adherence of either immotile or motile spermatozoa to mucus threads, to cells other than spermatozoa, or to debris is not considered agglutination and should not be recorded as such. The presence of agglutination is suggestive of, but not sufficient evidence to prove the existence of an immunological factor of fertility. When agglutination is observed, semen cultures and antibody assessment should be performed .



The major types of agglutination (WHO 2010): grade 1: isolated <10 spermatozoa per agglutinate, many free spermatozoa.grade 2: moderate 10–50 spermatozoa per agglutinate, free spermatozoa.grade 3: large agglutinates of >50 spermatozoa, some spermatozoa still free.grade 4: gross all spermatozoa agglutinated and agglutinates interconnected.

Progressive motility (PR): spermatozoa moving actively, either linearly or in a large circle, regardless of speed. Non-progressive motility (NP): all other patterns of motility with an absence of progression, e.g. swimming in small circles, the flagellar force hardly displacing the head, or when only a flagellar beat can be observed. Immotility (IM): no movement (). Lower reference limit (WHO 2010): The lower reference limit for total motility (PR + NP) is 40%. The lower reference limit for progressive motility (PR) is 32%.

Sperm morphology Many authors have gone as far as to argue that sperm morphology is a reflection of sperm functional competence and Sperm morphology assessment has been considered a valuable and stable method for predicting the in vivo and in vitro sperm fertilizing ability . Abnormalities of spermatozoa can be classified into head abnormality, neck/midpiece abnormality, tail abnormality, or the presence of cytoplasmic residue. These abnormalities can occur as a single defect or in a combination of two, three or all four abnormalities simultaneously. The reference value for normal sperm morphology determined by Kruger is >14% WHO1999 vs. 2010 the WHO reference values for normal sperm morphology is >4% .

Sperm vitality It is especially important for samples with less than about 40% progressively motile spermatozoa. The lower reference limit for vitality (membrane-intact spermatozoa) is 58 %( WHO 2010). Nowadays, there are several standard tests available for the assessment of the vitality of spermatozoa . One of these tests is based on the principle that dead spermatozoa take up the supravital red stain of eosin-Y, whereas living cells, regardless of their motility stage, will be unstained This assay reflects sperm membrane integrity, particularly the head region which takes up the red stain immediately

Endocrine Tests

The endocrine assessment of an infertile man includes measurements of serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), and perhaps other tests: Serum Testosterone Measurement of a morning serum total testosterone is usually sufficient. In men with borderline values, the measurement should be repeated and measurement of serum-free testosterone may be helpful. Serum Luteinizing Hormone and Follicle-Stimulating Hormone When the serum testosterone concentration is low, high serum FSH and LH concentrations indicate primary hypogonadism and values that are low or normal indicate secondary hypogonadism.

Other Hormones

Serum prolactin should be measured in any man with a low serum testosterone concentration and normal to low serum LH concentration. Although inhibin assays are not widely available outside of research laboratories, low serum inhibin concentrations may be an even more sensitive test of primary testicular dysfunction than high serum FSH concentrations, provided the assay is specific for inhibin B.

TERMINOLOGY

Male Infertility
Tx / Interventions: Treat underlying causes Intrauterine Insemination (IUI) Intracytoplasmic Sperm Injection (ICSI)

TREATMENT

Treatment of male infertility involves the couple. Specific endocrine treatment is available for men whose infertility results from hypogonadotropic hypogonadism. Hypogonadotropic hypogonadism due to hyperprolactinemia can often be corrected and fertility restored by lowering the serum prolactin concentration. If the hyperprolactinemia results from a medication, as is often the case, that medication should be discontinued, if possible. The hyperprolactinemia is caused by a lactotroph adenoma. It should be treated with a dopamine agonist, such as cabergoline or bromocriptine. The process of spermatogenesis normally takes 3 months. As a result, restoration of a normal sperm count usually does not occur for at least 3 and sometimes 6 months or more after the serum prolactin and testosterone concentrations have returned to normal. In some patients, who have a lactotroph macroadenoma, the hypogonadotropic hypogonadism appears to be the result of permanent damage to the gonadotroph cells by the mass effect of the adenoma. Gonadotropin treatment should be instituted for these patients.

Gonadotropin therapy: Treatment is initiated with human chorionic gonadotropin (hCG), 1,500–2,000 IU three times per week subcutaneously or intramuscularly for at least 6 months. hCG has the biologic activity of LH. The hCG dose should be adjusted upward according to symptoms of hypogonadism, serum testosterone concentrations, and semen parameters. Some patients with acquired hypogonadotropic states can be stimulated with hCG alone to produce sufficient sperm. If after 6–9 months the patient remains azoospermic or severely oligospermic, then human menopausal gonadotropin (hMG) or recombinant FSH should be added. • Pulsatile GnRH treatment: Pulsatile subcutaneous or intravenous treatment with GnRH has also been successfully used to treat gonadotropin deficient patients. GnRH has to be delivered in pulses using a portable pump with an attached catheter and needle for many months or years; most patients find it inconvenient to use GnRH therapy for so long.

Genital infection

Infertile men rarely present with symptoms or signs of acute genital infections or prostatitis, but they are sometimes diagnosed as having infections of the urogenital tract by the presence of increased leukocytes in the semen. Despite the absence of symptoms, we typically treat patients who have leukospermia, even if the culture is negative, with at least a 10-day course of antibiotics such as erythromycin or trimethoprim-sulfamethoxazole. A second course of therapy is usually given if leukocytes persist in the semen after antibiotics.

Sperm Autoimmunity

Continuous or intermittent high doses of prednisone (from 40 mg/ day to 80 mg/day) for up to 6 months have been shown in placebo-controlled trials to improve cumulative pregnancy significantly in partners of men with sperm autoantibodies. However, many patients cannot tolerate this regimen because of the adverse effects of high-dose corticosteroid therapy. As a result, most couples prefer to try an assisted reproductive technique, such as ICSI, as primary treatment for sperm autoimmunity.

Empirical Therapy

Many treatments have been used empirically for male infertility, including clomiphene citrate and other hormones and vitamins. Aromatase inhibitors may improve sperm concentrations in men with severe oligozoospermia or azoospermia prior to sperm retrieval for ICSI.

Female Infertility

Fecundability: probability of achieving a pregnancy within 1 menstrual cycle (25%) Fecundity: ability to achieve a live birth within 1 menstrual cycle (6%)

Female Infertility


Female Fertility
Causes Hypothalamus Pituitary Ovary Uterus Vagina Fallopian tube Cervix

Hypothalamic-Pituitary-Gonadal Axis

Female Infertility
Pituitary: Sheehan syndrome Tumors: Pituitary adenoma, metastatic Empty sella syndrome Inappropriate gonadal steroid feedback: estrogen excess: obesity/ tumors estrogen deficiency: aromatase deficiency/ ER gene mutation androgen excess: adrenal or ovarian Hyperprolactinaemia Thyroid dysfunction

Female Infertility

Hypothalamus: Stress Exercise Eating disorders Psychogenic Starvation/stress or severe illness Tumors (craniopharyngioma, metastatic tumor) Head injury Inflammation (sarcoidosis) Infection (tuberculosis) XRT Drugs

Female Infertility

OvaryGonadal dysgenesis - Turner’s Syndrome 45XO XRT / Chemo for childhood malignanciesPremature ovarian failure PCOS

Female Infertility

Uterine abnormalitiesMullerian Agenesis: Mayer-Rokitansky-Kuster-Hauser syndromeAsherman’s syndromeLeiomyoma Luteal phase deficiency

Female Infertility

Vaginal septum Tubal Disease Infections/ STD/PID Ruptured appendix Septic abortion Endometriosis Cervical

Investigations

Blood work: TSH PRL D3 FSH D3 LH Luteal phase Progesterone Imaging: Pelvic Ultrasound HSG Diagnostic Laparoscopy (later) Cervical(post coital test)

Marker of ovarian reserve

Ovulation testing

Ovulation Prediction Kit

Basal body temperature
Basal body temperature changes during the menstural cycle. Progesterone released during the menstrual cycle causes an abrupt increase in basal body temperature by 0.5°C at the time of ovulation.This enables identification of the fertile window through the use of commercial thermometers. •Progesterone levelmeasurement of progesterone in the second half of the cycle to help confirm ovulation

Treatment

Treat the underlying cause Medical Surgical

Medical treatments

DrugsClomipheneHuman menopausal gonadotropin, hMGFSHHuman chorionic gonadotropin, hCGGonadotropin – releasing hormone (Gn-RH) analogsAromatase inhibitorsMetforminBromocriptine


Gonadotropin-releasing hormone

Aromatase inhibitors

Gonadotropins

Human chorionic gonadotropin

COMPLICATIONS
Fertility drugs have the risk of multiple pregnancies Injectable fertility drugs increase the chance of multiple births Careful monitoring: blood tests, hormone tests, ultrasound measurement of ovarian follicle size Because of risk of ovarian hyperstimulation syndrome


is a medical condition affecting the ovaries of some women who take fertility medication to stimulate egg growth. Most cases are mild, but rarely the condition is severe and can lead to serious illness or death.OHSS is divided into the categories mild, moderate, severe, and critical. In mild forms of OHSS the ovaries are enlarged (5–12 cm) and there may be additional accumulation of ascites with mild abdominal distension, abdominal pain, nausea, and diarrhea. In severe forms of OHSS there may be hemoconcentration, thrombosis and distension,oliguria (decreased urine production), pleural effusion, and respiratory distress. Early OHSS develops before pregnancy testing and late OHSS is seen in early pregnancy.

Surgical treatment

Combined infertility
In some cases, both the man and woman may be infertile or sub-fertile, and the couple's infertility arises from the combination of these conditions. In other cases, the cause is suspected to be immunological or genetic; it may be that each partner is independently fertile but the couple cannot conceive together without assistance.

Unexplained infertility

Fertilization

Thank you




رفعت المحاضرة من قبل: Mubark Wilkins
المشاهدات: لقد قام 3 أعضاء و 201 زائراً بقراءة هذه المحاضرة








تسجيل دخول

أو
عبر الحساب الاعتيادي
الرجاء كتابة البريد الالكتروني بشكل صحيح
الرجاء كتابة كلمة المرور
لست عضواً في موقع محاضراتي؟
اضغط هنا للتسجيل