MOHD HANAFI SURYASUPERVISOR: RAJ DR. TAN NUGROHO MICHAEL CIPTO RIYANTO WONG ANGEL KWAN NUR AINURA CPC FATIN AKMAL
HISTORY • 33 | nullipara | obese • Fertility | after 5 years marriage • Menarche: 13 (regular)• Currently: Irregular menses | Weight gain • Day 2: FSH 3.5 mIU/ml | LH 5 mIU/ml
DEFINITION: INFERTILITYInfertility is defined as Primary happened failure to Infertility in woman conceive who has after one never year of conceived unprotected coitus at Secondary happened frequent Infertility in a woman intervals. who has conceived before
MALE: INFERTILITY ADVICES – 2nd most common cause – BMI > 29 may reduced fertility. – increased scrotal temperature. – excessive alcohol consumption (NICE,2004). – smoker’s sperm concentration is on average 13-17% lower than non-smokers. (Jenkins et. al 2003)
FEMALE: INFERTILITY ADVICES – declines with age. (NICE, 2004) – Moderate weight loss (Health Education Authority, 1996). – limit their alcohol intake (Jensen et al 1998). – stop smoking (RCOG, 1998). – Genital tract infection (Winter and Ahmad, 1998)
WHAT IS PCOS• Is a heterogenous disorder affecting the reproductive, endocrine and metabolic systems.• PCOS is often complicated by chronic anovulatory infertility and hyperandrogenism with the clinical manifestation of oligomenorrhoea, hirsutism and acne
PATHOPHYSIOLOGY: PCOSGenetically have insulin receptor disorderand thus insulin resistance-HYPERINSULINAEMIA During puberty- GH spurt- IGF1 ↑↑ Hyperinsulinaemia+IGF1 cause ovarian hyperstimulation Ovarian hyperstimulation- cause thecal cell hyperplasia and excessive androgen production
PATHOPHYSIOLOGY: PCOSHYPERINSULINAEMIA- also act on liver to reducesex hormone binding globulin (SHBG)- increasefree testosterone Increased LH production by anterior pituitary relative to FSH. Cause theca cell stimulation. Cyst formation Follicles do not mature due to premature surge in LH. Decreased FSH:LH cause inability of ovary to convert androgen to estrogen.
HOW TO DIAGNOSE: PCOS• Rotterdam criteria for diagnosis• The diagnosis of PCOS requires the exclusion of all other disorders that can result in menstrual irregularity and hyperandrogenism: congenital adrenal hyperplasia cushing syndrome androgen secreting tumours hyperprolactinaemia
HOW TO DIAGNOSE: PCOS Rotterdam criteria for diagnosis Two or more of the three following criteria: • polycystic ovaries (either 12 or more peripheral follicles or increased ovarian volume up to 10mm3)1 • -via TVUS • oligo- or anovulation (manifested as oligo- or amenorrhea)2 • clinical and/or biochemical signs of hyperandrogenism.3
CLINICAL AND/OR BIOCHEMICALSIGNS OF HYPERANDROGENISM Clinical Biochemical• Early sign-acne • Free serum• Later develop testosterone hirsuitism or level (not more even male than 5nmol/L) pattern alopecia
A raised luteinising hormone/follicle- stimulating hormone ratio (LH:FSH 2:1) is NO LONGER a diagnostic criteria!!!!
SCENARIO • Husband: Seminal fluid – severe oligoasthenoteratoazoospermia • Day 21 serum progesterone – not ovulating• Ovarian stimulating induction + IVF
PREPARATION: SEMEN SAMPLING• Advice patient - abstinence from sex and masturbation for 2 - 7 days prior• collected in a private room near the laboratory to limit the exposure of the semen to fluctuations in temperature and to control the time between collection and analysis• semen sample needs to be complete & should report any loss of any fraction of the sample
COLLECTION: SEMEN SAMPLING• obtained by masturbation and ejaculated into a clean and wide mouthed container• specimen container should be kept at ambient temperature, between 20 C and 37 C• placed on the bench or in an incubator (37 C) while the semen liquefies.
HOME: SEMEN COLLECTION • Sample need to be completed. Report if incomplete. • Record the time of semen production and sent to lab within 1H. Temperature kept between 20 C and 37 C during transport of sample • Noted at report place of collection (home / outside the lab)
CONDOM: SEMEN COLLECTION • Collected in a condom during sexual intercourse • Only special non-toxic condoms designed used • Information on how to use the condom, close it, and send or transport it to the laboratory. • Record the time of semen production and sent to lab within 1H. Temperature kept between 20 C and 37 C during transport of sample • Noted at report place of collection (home / outside the lab)
SEMEN ANALYSIS: WHO Volume • > 1.5 mL pH • ≥ 7.2 Total Sperm • 39 × 10^6 spermatozoa per Number ejaculate Sperm • 15 × 10^6 spermatozoa per mlConcentration
SEMEN ANALYSIS: WHO 2010• Sperm Motility : – 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. – Total motility (PR + NP) is 40% – Progressive motility (PR) is 32%
SEMEN ANALYSIS: WHO 2010• Sperm Vitality (membrane-intact spermatozoa): 58% or more• Sperm Normal Morphology (regular oval head, with a connecting mid-piece and a long straight tail): > 4%
NOMENCLATURE: WHO 2010• Normozoospermia: total number of spermatozoa, and % of progressively motile (PR) and morphologically normal spermatozoa ≥ lower reference limits• Oligozoospermia: Total number of spermatozoa <39 106 spermatozoa per ejaculate or concentration of spermatozoa <15 106 spermatozoa per ml• Asthenozoospermia: Progressively motile (PR) spermatozoa <32%
NOMENCLATURE: WHO 2010• Teratozoospermia: < 4% morphologically normal spermatozoa• Azoospermia: No spermatozoa in the ejaculate• Aspermia: no semen (no or retrograde ejaculation)
OLIGOASTHENOTERATOZOOSPERMIA• Total number/concentration of spermatozoa, and percentages of both progressively motile (PR) and morphologically normal spermatozoa, below the lower reference limits
COMMENT ON THE REASON OF USING4 DAY 21 PROGESTERONE TEST
CRITERIA FOR TEST1. Normal menstrual cycle2. Length of menstrual cycle (28 days)3. Not on hormonal therapy/OCP/ hormonal contraception interfere normal hormonal changes4. If on OCP, stop at least 1 month before test
Ideal progesterone test done 21 days afterbreeding(Progesterone is high)
- Normal Day 21 progesterone level in functioning corpus luteum > 30ng/ml- ↓ Day 21 progesterone level Anovulatory cycles (no ovulation & no corpus luteum formation to secrete the progesterone) Abnormal menstrual cycle Length of the menstrual cycle On hormonal therapy/OCP/ hormonal contraception
INDICATIONS OF IVF• Tubal problems: blocked or damaged Fallopian tubes• Severe endometriosis• Pelvic inflammatory disease with severe adhesion• Male factor• Unexplained infertility
COMPLICATIONS OF IVF• IVF is basically a safe procedure.• As with any medical or surgical procedure, a few patients undergoing IVF treatment will experience side effects and complications.• The most common complications associated with IVF treatment are the: Failure of treatment The possibility of ectopic pregnancy. Ovarian hyperstimulation Bladder, bowel injury and other Multiple pregnancy, risk related to egg retrieval
WHAT IS IVF?The steps of IVF are as follows:• Ovulation Induction• Retrieval• Insemination of eggs and embryos culture• Transferring embryos to the uterus
OVULATION INDUCTION• optional if women can ovulate normally• the stimulatory phase of an IVF cycle must begin on the third day of the menstrual cycle.• patients receive daily injections of gonadotropins – hormones, which stimulate your ovaries to produce multiple eggs.• The ultimate goal of IVF stimulation is to achieve the maximum number of mature follicles- eggs- without over stimulation.
OVARIAN HYPERSTIMULATION SYNDROME (OHSS) Mild to Moderate majority of women have a mild or moderate form of the syndrome and invariably resolve within a few days unless pregnancy occurs, that may delay recovery. complain of pain, a bloated feeling and mild abdominal swelling. In a small proportion of women, the degree of discomfort
OVARIAN HYPERSTIMULATION SYNDROME (OHSS) Severe Very rarely is severe and the ovaries are very swollen. The woman will feel ill, with nausea and vomiting, abdominal pain. Fluid accumulates in the abdominal cavity and chest, causing abdominal swelling and shortness of breath. Reduction in the amount of urine produced. These complications require urgent hospital admission to restore the fluid and electrolyte balance, monitor progress, control pain and in some very serious cases, termination of pregnancy. Complications associated with severe OHHS include blood clotting disorders, kidney damage and twisted ovary (ovarian torsion).
CAUSES OF OHSS Women with polycystic ovaries. Over response to fertility drugs. Young thin women.High estrogen hormone levels and a large number of follicles or eggs. Administration of GnRh agonist. The use of hCG for luteal phase support.
RETRIEVAL When the eggs are“ready”, that is, the majority Mature eggs will be collected that we ask the male partner of eggs are ripe for by ultrasound guided needle to produce a semen sample harvesting but they are not aspiration. yet truly mature. Retrieval is done after atleast 3 mature follicles of 18 It is at this time, shortly This technique is performed mm or more to produce a rafter the conclusion of the in the office with IV sedation.mature egg, a final injection egg retrieval, must be taken. minor surgical-Follicles are located by ultrasound and then a needle is guidedThis final shot is called HCG. through the vaginal wall into the ovary to aspirate the eggs from the follicles.
INSEMINATION OF EGGS AND EMBRYO CULTURE ICSI IVF intracytoplasmic sperm injection In-Vitro Fertilisationinject a single sperm into each egg. decision regarding the number of embryos to transfer is not always easy 48 hours the fertilized eggs – now depends on such things as patient age, past IVFcalled embryos – will be left alone in cycles and the quality of the embryos. the incubator- for 3 to 5 days. objective is to maximize the chance of pregnancythe embryos will have been carefully while minimizing the chances of multiple examined pregnancies.
TRANSFERRING EMBRYOS TO UTERUSthe embryos will be transferred by placing very smallflexible catheter into your cervix and injecting theembryos. continue to take Progesterone (shots, pills or pessaries) A pregnancy test will be done 2 weeks after the transfer If the test is positive Progesterone shots are continued as instructed (serum B-HCG).
6TH WEEK AFTER IVF• c/o lower abdominal pain associated with per vaginal bleed for 2/7• pain more marked on right side radiated to the back • vomited several times • pain temporarily relieved by analgesia
ON EXAMINATION • Blood pressure: 90/60 mmHg (↓) • Pulse rate: 110 beats per minute (↑)• Abdomen examination: tender on the right iliac fossa (RIF) with no mass palpable• Vaginal examination: cervical os was closed with some old blood seen on posterior fornix • Minimal cervical excitation and no adnexal mass palpable
Ectopic pregnancy• Pregnancy occurring in sites other than endometrium of the uterus.Threatened miscarriage• Vaginal bleeding (usually fresh bleed and painless) with a closed cervix prior to 22 weeks of pregnancyMolar pregnancy• Pregnancy in which a hydatid mole develops from the trophoblastic tissue of the early embryonic stage of developmentImpending miscarriage (inevitable)• Onset of miscarriage process and will end as either complete, incomplete or septic miscarriage
EVENTUALLY• An emergency laparatomy was done and found to have 2 litres of haemoperitonium and ectopic pregnancy of right tube.• Subsequently, right salphingectomy was done and she was discharged after 3 days from ward.