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MRCOG PART 2 SBAs and EMQs

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Essay 238 - Infertility

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		Posted by Mohammad H. Tue Jul 17, 2007 10:05 am
26 year old woman and her 32 year old partner suffer from infertility due to anovulation. (a) Logically outline the likely causes [5 marks]. (b) Logically outline your investigations to identify the cause of anovulation [6 marks]. (c) Evaluate the treatment options to enable the couple to have a child [9 marks]. Causes of anovulation may be ovarian,pituitary,hypothalamic or systemic . Ovarian causes include polycystic ovary syndrome ,premature ovarian faliure that may be idiopathic or due to Turner,syndrome ;galactosemiaor iatrogenic as in cases of radiotherapy or chemotherapyand in cases with absent ovaries as androgen insensetivity syndrome(AIS) Pituitary causes include hyperprolactinaemia due to micro or macro pituitary adenoma ,Sheehan\' syndrome (panhypopituitirsim). Hypothalamic causes as in anorexia nervosa ,or in cases of weight loss (more than 25% loss of original weight),Kallman;syndrome and in tumors that destruct hypothalamic-pituitary course. Systemic causes as hypothyroidism , any chronic deblitating disease as ( chronic renal faliure,heart faliure or uncontrolled diabetes or auto immune disease). INVESTIGATIONS Hormonal profile including prolactin( to asess hyperprolactinemia that is mildly elevated in PCOD and highly elevated in pituitary tumors),thyroid function test (to exclude thyriod problems),gonadotrophins (FSH &LH are expected to be elevated in primary ovarian cases ,FSH/LH ratio>2 in cases of PCOD and to be low in hypothalamic and pituitary cases),androgen which is increased in PCOD and AIS,estrogen and progesterone levels . Ultrasound scanning to detect polycystic ovaries , streak or absent ovaries. Skull x-ray , CT,MRI in cases where pituitary or hypothalamic tumors are suspected . Karyotyping in suspected Turner\'s ,Kallman\'s or AIS Investigations directed towards the suspected systemic cause . TREATMENT For PCOS weight reduction in overweight patients can induce ovulation and improve hormonal profile ,ovulation induction using clomiphene citrate is associated with ~60% sucess in ovulation induction ,gonadotrophins and gonadotrophin releasing homone agonbist in cases of clomiphene resistance , ovarian drilling associated with induction of ovulation without increase in the risk of multiple pregnancy and metformin an that induce ovulation and reduce insulin resistance . In casesc f hyperprolactinaemia ,bromocryptine is the drug of choice to induce ovulation and it can reduce the size of prolactinoma. In cases of weight related anovulation weight gain should be tried before use of ovulatin inducing drug that can be used after patient is above 45 kg . In cases of ovarian faliure IVF with ovum donation is an option for the patient .Treatment of thyroid disorder or other general cause. in cases of AIS adoption is an option hat can eb discussed.
		Posted by ratna N. Tue Jul 17, 2007 02:08 pm
Anovulation is the principal cause of infertility in 1/5th of subfertile couple.The likely causes can be classified on the basis of anatomical site in the hypothalamo-pituitary-ovarian axis where the deficiency exists. Hypothalamic causes: ammenorhea related to stress and weight loss, Kallman syndrome,isolated gonadotrophin deficiencyand idiopathic hypogonadotrophic hypogonadism. Pituitary causes: tumours, necrosis and thrombosis. Hypothalamic pituitary dysfunction: Polycystic ovarian syndrome with associated endocrine disturbances. Ovarian failure: genetic,autoimmune,secondary to chemotherapy and premature menopause. Pointers in the history which includes a detailed menstrual history regarding cyclicity ,bouts of amenorrhoea and clinical examination which will reveal stigmata of polycystic ovarian syndrome,hyperprolactinaemia and anorexia will dtermine the investigations. Regular menstruation is strongly suggestive of ovulation but is not conclusive.A day 21 progesterone showing a level of> 30nmol/l when periods are regular confirms ovulation. If the periods are irregular serial progesterone tracking should be done.If this lady has oligomenorrhoea,primary or secondary amennorhoeaearly referral to a specialist infertility clinic with access toendocrine laboratory facilties and ultrasonography is advisable. Pituitary causes in such cases is assessed by measurement of LH, FSH,prolactin and thyroid funtion on day 2 or 3 of a menstrual period, when absent, after a induced bleed with a short course of progesterone.If a withdrawal bleed occurs then the endometrium is sufficiently oestrogenised, if no bleed occurs it could be due to decreased oestrogen from hypogonadal hypogonadism or decreased FSH LH due to anorexia and stress. FSH may be normal with elevated LH suggests polycystic ovarian syndrome confirmed by measuring androgens sex binding globulin and ovarian ultrasound. She may also exhibit mild elevation of prolactin ,but elevated levels must always be assumed to be caused by pituitary prolactinoma until proven otherwise.A clinical history of galactorrhoea,tunnel vision with amennorhoea, headacheshould prompt imaging of pituitary fosa by MRI. If both FSH LH are elevated possibility of premature ovarian failure should be thought of. She may have menopausal symtoms, famly history and there maybe exposure to pelvic irradiation or chemotherapy. Diagnosis should be confirmed by repeated measurements of gonadotrophinsand oestradiol and a karyotype to rule out Turners mosaics. The treatment would include ovulation induction , before which other considerations should be given importance such as; Relevant investigations to select the approprite treatment, patient couselling especially regarding risks of ovarian hyperstimulation syndrome,multiple pregnancy,possibility of fetal reduction and putative risk of cancer. Ovulation induction either with antioestrogens, gonadotrophins or GnRH agonists if adequate monitoring faclities such as endocrinology and ultrasonography are present to diagnose ovarian hyperstimulation and other ealy pregnancy complications.Protocols for reducing risks, particularlyfor cancelling cycles to preventmultiple gestation and OHSS.Any male factor problems and a semen analysis should be assessed .Tubal patency using hysterosalpingagraphyin low risk and lapaoscopy and dye when endometriosis and adhesions are suspected or if no conception occursafter six treatment cycleswith clomiphene and ovulation confirmed.Advice if her BMI is over 30kg/m2 to reduce weight as it increases he spontaneous ovulation and pregnancy rates,but also evokes better response to ovulation induction regimens.
		Posted by Radhika A. Tue Jul 17, 2007 05:32 pm
A 26 year old woman and her 32 year old partner suffer from infertility due to anovulation. (a) Logically outline the likely causes [5 marks]. (b) Logically outline your investigations to identify the cause of anovulation [6 marks]. (c) Evaluate the treatment options to enable the couple to have a child [9 marks]. a) The causes of anovulation could be categorised as those due to hypothalamo-pituitary causes, hypothyroidism,ovarian reasons. Hypothalamo-pituitary causes : Hypothalamic Acquired - Sudden severe weight loss due to exercise or starvation, mental stress, following infections like encephalitis, trauma. Congenital : Congenital absence of releasing hormones Pituitary causes : Prolactinomas causing continuous high levels of prolactin inhibiting pulsatile synthesis of gonadotrophins, craniopharyngioma Congenital : empty sell syndrome Hypothyroidism may also be acquired or congenital; also results in the inhibition of the pulsatile gonadotrophin synthesis Ovarian causes of anovulation include chromosomal abnormalities eg Turner\'s syndrome (early follicular atresia), B galactosemia, viral illnesses and cancer chemotherapeutic agents causing premature ovarian failure or idiopathic premature ovarian failure, polycystic ovaries, adult onset adrenal hyperplasia b)Investigations to identify the cause : Clinical evidence for prolactinomas ( galactorrhea, headache, difficulty in vision), hypothyroidism ( weight gain, lethargy) and symptoms of hypogonadism should specifically elicited, weight gain , menstrual irregularity and hirsuitis pointing towards PCOS/CAH. The priority of investigations would proceed as per the presenting features. I would like to get a day 2/3 transvaginal sonography done to assess the ovarian volume, substance and look for any evidence of polycystic ovaries.I would like to get the hormonal profile to start with thyroid function tests and serum prolactin levels in the presence of galactorrhea . CT scan of the brain would confirm a prolactinoma.In the presence of clinical suspicion of PCOS, serum free and total testosterone with glucose tolerance test and fasting insulin levels need to be done. In the presence of evidence of ovarian failure or if the results are normal, serum FSH/LH and serum estradiol levels confirm ovarian failure. c) The treatment options available are the treatment of the original reason for anovulation. 1. Prolactinomas - I would like to start her on bromocriptin starting with lower doses slowly increasing upto 7.5 mg per day. Ovulation may be acheived at lower doses. Cabergoline as per the existing evidence is better avoided in people planning pregnancy since safety profile in early pregnancy is yet nor proven. 2. Hypothyroidism needs to be corrected with l- thyroxine . Repeat thyroid profiles need to be done after at least 1 month after starting treatment. 3. PCOS : In case of obesity , I would like to advise her to take measures to lose weight since loss of even 10% weight is known to be beneficial. I would also like to start her on Metformin for at least three months to assist weight loss, increase chances of ovulation. In case the above measures fail to acheive ovulation, I would like to induce ovulation with clomiphene initially going on to gonadotrophins and GnRha after maximum of 200mg of clomiphene if ovulation is not acheived. Prior to ovulation induction, I would like to confirnm tubal patency with a Hysterosalpingogram and also confirm normal semen parameters.
		Posted by Valerie T. Tue Jul 17, 2007 10:10 pm
A 26 year old woman and her 32 year old partner suffer from infertility due to anovulation. (a) Logically outline the likely causes [5 marks]. (b) Logically outline your investigations to identify the cause of anovulation [6 marks]. (c) Evaluate the treatment options to enable the couple to have a child [9 marks]. a) The causes of the anovulation infertility can be divided into the following categories: hypergonadotrophic hypogonadism, hypogonadotrophic hypogonadism, ovarian dysfunction and endocine causes. Hypergonadotrophic hypogonadism is caused by failure of the ovary to respond to gonadotrophin hormones. The absence of the negative feedback from follicular inhibin B and oestradiol, leads to the pituitary gland producing excessive amounts of gonadotrohin hormines. Premature ovarian failure and resistant ovary syndrome are conditions that cause hypergonadotrophic hypogonadism. Hypogonadotrophic hypogonadism is caused by failure of the pituitary gland to produce gonadotrophin hormones. This can be due to destruction of the pituitary gland by infection eg. tuberculosis, by ischemia eg Sheehan\'s syndrome, by tumour eg craniopharyngioma or by radiation of the brain. Hypothalmic dysfunction can lead to a decrease or no production of gonadotrophic releasing hormone, eg excessive exercise, stress or anorexia nervosa. Causes of hypogonadotrophic hypogonadism may also be congenital eg Kallmann\'s syndrome. Ovarian dysfunction can be caused by polycystic ovary syndrome. Endocrine causes such as hyperprolactinemia and hypothyroidism can cause anovulation. b) I would calculate the body mass index. I would do the luteinizing hormone and follicle stimulating hormone blood tests. They should be done between the 2nd and 4th day of the menstrual period. I would do a serum progesterone blood test on day 21 of a regular 28 day menstrual cycle. Levels in excess of 30 nmol/l will indicate that ovulation has occurred. If the cycle was irregular or not lasting for 28 days, I would do serial progesterone tests. I would do a prolactin blood test. If there were symptoms of hypothyroidism, I would do thyroid function tests. I would do an ultrasound scan to identify any ovarian pathology such as polycyctic ovaries. c) The treatment option depends on the cause of the anovulation. In cases of hypergonadotrophic hypogonadism such as premature ovarian syndrome and resistant ovary syndrome, the treatment that can be offered is oocyte donation. These cases will not respond to ovulation induction. Hypogonadotrophic hypogonadism. Normalization of body weight in those with excessive weight loss will result in ovulation without need of medical intervention. Ovulation induction can be achieved with the pulsatile administration of GnRH or daily administration of gonadotrophins. Prolactioma can be treated medically. If the cause is polycstic ovary syndrome (PCOS) and the patient has an elevated BMI, weight loss would be beneficial. 80% of women with PCOS and obesity, have achieved ovulation after the weight has returned to normal. Anovulation in PCOS can also be treated medically using Clomiphene, GnRH or gonadotrophins. Clompihene is very effective, however it is associated with side effects and there is an increased risk of multiple pregnancies and OHSS. Surgical methods can also be used to treat anovulation in PCOS. These methods are wedge resection and ovarian drilling. Wedge resection has been shown to be effective in treating anovulation, however it has been associated with many complications such as tubal damage and adhesions. The complications outweigh the benefits of the procedure. Ovarian drilling has been shown to be very effective and associated with less complications than wedge resection. There is also a reduced risk of multiple pregnancy and ovarian hormone hyperstimulation syndrome.
		Posted by Malar R. Wed Jul 18, 2007 07:32 am
The causes of anovulation can arise from abnormalities at different levels of the hypothalamic- pituitary-ovarian axis. The commonest cause of anovulation is polycystic ovarian syndrome which is at the ovarian level. The ovaries can also fail to ovulate in premature ovarian failure secondary to causes such as previous irradiation and chemotherapy or karyotyping problems as in Turner\'s syndrome. Chronic illness, low BMI, anorexia nervosa and excessive exercise can lead to hypothalamic suppression and lead to anovulation.Pituitary tumours can suppress pituitary function and lead to anovulation by the overproduction of prolactin.Also previos meningitis can affect the hypothalamus and pituitary gland and stop GnRH release and stop ovulation. Serum FSH should be performed as a high level might indicate premature ovarian failure and should be repeated in 6 weeks to confirm persistent high levels. LH levels should be done and a high LH:FSH ratio might be suggestive of PCOS. Serum prolactin if more than 500 can be linked with a prolactinoma which if susoected needs to be investigated further with a brain MRI.Low Sex hormone binding globulin and high testosterone levels might indicate PCOS. USS of pelvis can indicate polycystic ovarian morphology.The patient\'s blood can also be karyotyped to look for Turner\'s syndrome if clinically suspected.The patient\'s BMI should be calculated and a BMI of less than 18 might be suggestive of anovulation due to hypothalamic anovulation. The options of treatment depend on the cause of the anovulation. In PCOS, the patient should be advised to lose weight as this can spontaneously achieve ovulation.This requires patient motivation and weight loss can be achieved better in a weight loss programme with a dietician input.Also she should be advised to stop smoking as this also improves ovulation. Clomifene, an anti oetrogen, can be started in PCOS. This can achieve ovulation in about 60% of patients but not all of them manage to conceive. It is cheap but is associated with multiple pregnancy and a small risk of ovarian hyperstimulation syndrome. It requires monitoring of follicles by transvaginal scanning to minimise risk of hyperstimulation. Clomifene has also been tries in conjunction with metformin to improve ovulation. There is currently limited data on the success rate of achieving pregnancy on this regime. It is suggested that this regime might increase the rate of ovulation.Metformin is safe and requires liver function monitoring at the start of treatment. Intrauterine insemmination is an option combined with ovulation induction with clomifene in PCOS. 4 cycles of treatment can achieve cummulative pregnancy rates of 22%.This regime requires regular monitoring in hospital but is not as expensive as in vitro fertilisation. GnRH analogues can be used to stimulate ovulation. They are effective but are associated with a risk of multiple pregnancy and ovarian hyperstimulation. They can cause thrombocytopenia and osteoporosis and their use is limited to a amximum of 6 months.They require intense monitring in hospital. Laparoscopic ovarian drilling can also achieve ovulation rates similar to GnRH analogues. They however carry operative risks but do not cause ovarian hyperstimulation. In vitro fertilisation is another option which can achieve conception rates of about 20% per cycle. It is expensive and requires intensive hospital monitoring with the risks of ovarian hyperstimulation and multiple pregnancy. If the cause of anovulation is premature menopause (previous ovarian iradiation/Turner\'s syndrome), then egg donation is an option followed by IVF and embryo replacement. The success rate is about 22% per treatment cycle but is expensive. In the case of a prolactinoma, it can be treated medically with bromocriptine or cabergoline or surgically if it is a macroadenoma.Ovulation would be expected to recover after treatment and fertility should return to normal. Hypothalamic suppression due to low BMI or chronic illness can be corrected by treating the cause. Weight gain is associated with spontaneous ovulation and conception.Optimising chronic illness can also restore fertility but this might be difficult as in cystic fibrosis or chronic renal failure.
		Posted by Idris O. Wed Jul 18, 2007 08:54 am
a) The causes of anovulatory infertility include hypothalamic pituitary failure which may be due to anorexia nervosa with BMI<19. It may also be caused by hypothalamic pituitary dysfunction caused by PCOS if the patient is overweight and have features of hyper androgenism. The third cause would be ovarian failure which may be due to Turner\'s syndrome, mumps during adolescent or pelvic tuberculosis. The presence of galactorrhoea with features of raised intracranial pressure may suggest hyperprolactinaemia with a prolactinoma. In the latter, use of drugs which increase prolactin levels should be enquired like anti-depressants, anti-psychotic drugs and anti-hypertensives like methyl-dopa. Enquire about symptons of thyroid disease in particular hypothyroidism which also causes hyperprolactinaemia. b) Investigation would be directed to determine the cause of the anovulation. A pelvic USS would suggest PCO if ovarian volume >10cm3 or presence of > 12 follicles at the periphery of the ovary. It can also diagnose streaked ovaries in Turner\'s syndrome. Hormonal profile with menstrual FSH and LH and oestradiol would be low in anorexia nervosa. There would be high LH relative to FSH ( ratio 3/1) in PCOS in addition to increase free androgen index and androstenedione. The FSH level is raised > 20 iu/l in ovarian failure. Serum prolactin levels usually in excess of 2000miu/ml in prolacinoma and imaging with CT/MRI may be required. Free T4 and TSH with serum prolactin if there are symptoms of thyroid disease. Mid -luteal phase progesterone usually < 30mM/l performed on two occassions confirms anovulation. c) Treatment would be arranged in a specialised fertility centre to optimize the best chances of fertility. General measures include commence supplemental folic acid 400mcg daily until 3/12 of pregnancy(5mg if on anti-epileptic drug or previous baby with neural defects). Rubella screening and offer immunisation and postpone pregnancy by 1month. Cervical smear as opportunitistic sreening if none since the age of 25years. Life style modification with reduction in alcohol intake and stopping smoking(refer smoking cessation group). Maintain BMI between 20-25 with good diet and exercise. Hyperprolactinaemia is treated with stopping anti-dopaminergic drugs the patient is taking and use of dopamine agonists. Bromocriptine is less well tolerated because of side effects and cabergoline or the newer drug quinagolide may have to be tried. Macroadenoma is treated with transphenoidal hypophysectomy in addition to bromocriptine or cabergoline. Hypothyroidism is treated with L-thyroxine. Oocyte donation would be necessary in ovarian failure. Restoration of body weight would restore ovulation in anorexia nervosa and rarely may require pulsatile GnRH analogue. Treatment of anovulation in polycystic ovarian syndrome usually initiated with weight reduction if BMI>30. This may bring about spontaneous ovulation or improve the effectiveness and reduce the side effects of ovulation induction drugs. Clomiphene citrate remains the first line drug with ovulation rate of 70-85% but conception rate of only 40-50% due to its anti-oestrogenic effect on the cervical mucus and the endometrium. The risk of multiple pregnancy is 11% and risk of OHSS very small. Patients who ovulate but not pregnant after 6 courses of clomiphene should be offered IUI with clomiphene because it increases pregnancy rate. Patients who have not responded to clomiphene and have a BMI>25 should be offered clomiphene and metformin since increases ovulation and pregnancy rates. Clomiphene citrate is not usually recommended for use > 12months because of the small risk of ovarian cancer.Tamoxifen may be used in patients that cannot tolerate clomiphene. Gonadotrophin is used as second line for ovulation induction to treat refractory anovulation. It is associated with increased risk of multiple pregnancy (20%) and OHSS and close monitoring required. Though effective associated with increased cost. GnRH analogues with/without gonadotrophins is used in IVF cycles to prevent spontaneous LH surge. This reduces cancellation rate and increase pregnancy rate per treatment cycle but associated with increase multiple pregnancy and OHSS. It\'s usefulness is also limited by cost. Surgical treatment with ovarian drillng is usually a last consideration and is as effective as gonadotrophin treatment and more cost-effective with no additional risk of OHSS or multiple pregnancy. It is however associated with anaesthetic risk especially in the obese patient and risk of adhesion formation from the operation. The risks of long term ovarian failure or ovarian carcinoma is not known. The last option opened to this patient is adoption. Written information would be provided for this discussion and contact details of support group. A follow up would also be arranged.
		Posted by Saad A. Wed Jul 18, 2007 05:18 pm
The causes can be hypergonadatotrophic anovulation (ovarian failure), hypothalamic pituitary dysfunction (normo gonadotrophic anovulation) and hypothalamic pituitary failure (hypothalamic anovulation) and hyperprolactinemic anovulatin .The cause of ovarian failure could be premature ovarian failure (POF) due to chromosomal abnormality (Turner?s syndrome), iatrogenic due to radio and chemo therapy, auto immune disorders and resistant ovaries .The second cause could be due to normogonadotrohic anovulation includes polycystic ovary. The third hypogonadotrophic failure causes are cranial tumours like cranio phyrangiomas, trauma like Sheehan?s syndrome, Kallman syndrome (GnRH neuron defect). The fourth group is hyper prolactinemic an ovulation include macro/micro adenoma drugs which induce hyper prolactinemia (benzodiazepine for Schizophrenia, metoclopramide, and cimitidine. b. The investigations are done after detailed history and examination. The patient should have her tubal patency test and semen analysis. FSH and LH if raised indicate ovarian failure; these are raised in case of POF, resistant ovaries, streak ovary (Turner). LH: FSH ratio is raised in polycystic ovary. FSH, LH levels are low in cranial tumours, Kallman syndromes. Karyotyping is required to identify chromosomal disorders like Turner?s syndrome. Prolactin levels are checked to detect prolactinemia and other causes. CT scans, MRI are needed for size and location of micro and macro adenoma. Ultrasound is needed for polycystic ovaries although the scan might be negative. Testosterone, DHEAS, estradiol is also needed for ovarian polycystic disease diagnosis. Ovarian biopsy is need for diagnosis of resistant ovaries but is not usually done. c. The treatment is according to the cause. For polycystic ovaries weight loss is needed in obese. Medical and non medical methods of ovulation induction are used. Clomiphene (50-100mg) for 2-5 days of the cycle(6 cycles) cause 60-80% pregnancy rate and cumulative conception rate is 40-50%. It is associated with multiple pregnancies in 5-10% and miscarriage is 10-20%. There is risk of ovarian cancer (after 12 cycle use). Gonadotrophins are used if not responding to clomiphene. HMG (nomegone,puregone) recombinant FSH (metrodine) if used in 75 u dose is effective. Follicular tracking and estradiol levels are needed to be monitored to prevent ovarian OHSS syndrome. There is increased risk of multiple pregnancies (20-25%).The cumulative conception rate is 50-60%. Laparoscopic ovarian drilling has same efficacy as gonadotrophin .There is no need for monitoring of estradiol or follicular tracking and no risk of multiple pregnancies and OHSS. The effect is uptil 6-12 months. There is 30-40% miscarriage rate, but there are risks associated with anaesthesia and operation like adhesion, haemorrhage and VTE. Metformin is used in obese patients for an ovulation. Aromatase inhibitors (letrozole) are under trial.If cause is hpyper prolactinemia bromocriptine is effective but is associated with side effects like nausea, vomiting and Raynaud?s syndrome. However carbergoline is very effective if given twice daily. For macro adenoma if large is treated by neuro surgeon .If patient is using drugs they should be stopped. In case of ovarian failure oocyte donation is advised after detailed counselling of patient and partner. If the above measures failed the patient and partner are advised for artificial reproductive techniques like IVF.Adoption can also be advised but it is associated with moral and ethical issues.
		Posted by AMNA K. Thu Jul 19, 2007 04:34 am
a.) Causes of anovulation can be divided broadly into hypgonadotrpohic hypogonadaism in which pituitary gland fails to produce gonadotrophins leading to the lack of ovarian stimulation. This could be congenital (kallman syndrome)or acquired due to damage to the pituitary gland by tumor, (benign non functioning adenoma/cranio pharanginoma) inflammation (Tuberculosis),ischemia of pituitary gland(seehan,s syndrom) or radiotherapy of brain. Hypothalamic dysfunction (excessive exercise, psychological stress, anorexia nervosa) can also lead to hypogonadotrophic hypogonadism. An ovulation could be because of normogonadotrophic hypogonadism which mostly include patients with polycystic ovarian syndrome(PCOS) and patients with congenital adrenal hyperplasia, adrenal tumors and androgen producing ovarian tumors Hypergonadotrphic hypogonadism which includes premature ovarian failure or its variant ovarian resistant syndrome can also be the cause of anovulation. b.) Investigations advised depend upon clinical suspicion of diagnosis and include serum FSH and LH levels on day 1-3 . An elevated level(normal is 2-10IU/l FSH and for LH is 2-14 IU/l) of both hormones is highly suggestive of impending/ premature ovarian failure(POF). On the other hand elevated level of LH indicates polycystic ovarian syndrome(PCOS) as it is elevated in 40% of patients with PCOS. Previous criteria of an elevated ratio of LH :FSH of>2 :1 for the diagnosis of PCOS is no more applied now. Raised androgen (testosterone, androstenedion) also point to PCOS. Elevated levels of DEHA-S is also seen in patients with PCOS. Insulin r?sistance occurs in 30 to 60% of cases of PCOS so raised fasting insulin level can also help to diagnose it Normal levels of serum prolactin(4oo 600U/l) excludes hyperprolactenemia as a cause of anovulation and if serum prolactin level is 1000U/l then CT/MRI of pitutary fossa is advised to exclude pituitary tumours. In 20% of patients with PCOS serum prolactin level is raised. Pelvic USS is requested for characteristic morphology of PCOS(10 or more follicles of <10mm in diameter in each ovary arranged around anecho dense stroma and ovarian volume of 10cm). Patient,s karyotyping is advised if raised level of serum gonadotrophins(30 IU/l) is found to diagnose Turner syndrome as a cause of POF.Thyroid function test will be advised if patient is symptomatic. c.) Treatment options depend upon the cause identified. If PCOS is the diagnosis and her body mass index (BMI) is high(>25kg/m) then weight reduction, diet alterations and exercise will be advised. If normal BMI or no response after weight reduction then medical induction of ovulation with chlomiphen citrate which is the first drug of choice in a dose of 50-150mg orally from day 2-6 for maximum 12 cycles can be prescribed .It should only be advised if there is an access to ultrasound monitoring to reduce the risk of multiple pregnancy. It induces ovulation in 70%-85% of the cases with 40%-50% conception rate. However is associated with side affects of hot flushes and visual disturbances and twin pregnancy(1-5%). Patient must be counseled about putative risk of ovarian cancer if therapy is continued beyond 12 cycles(NICE ). Another drug that can be advised is metformin(insulin sensitizer) with potential advantage of unifollicular ovulation and increased insulin sensitivity although associated with few side effects(nausea , vomiting, flatulence) If chlomiphene citrate and metformin fail to induce then gonadotrophins (both recombinant and human menopausal gonadotrophin) can effectively induce ovulation ,there is an ncreased risk of multiple pregnancy and ovarian hyper stimulation syndrome(OHSS) so need uss monitoring for follicular tracking. Laparoscopic ovarian drilling(LOD) is another option if medical induction of ovulation fails and has an advantage of not requiring ultrasound follicular tracking and induces ovulation in 80% of the patients with normalization of leutinizing hormone concentration and good pregnancy rate (40%-69%), but is associated with inherent risk of anesthesia and surgical risks(bowel, bladder and blood vessel injury). Option of gonadotrophin with or without intrauterine insemination or in vitro fertilization can be offered if all other strategies to induce ovulation fail. Hyperprolactinoma can be treated with dopamine agonist(bromocriptine or cebergoline) . Side effects associated with bromocriptine( mostly GIT) are tolerable if taken with food. Rarely surgery is required in drug resistant cases cebergoline has a better side effect profile and compliance.. If POFis the diagnosis then ovum donation after appropriate counseling can be advised.Option of adoption can be discussed with the patient if needed.
		Posted by Dr Mamta D. Thu Jul 19, 2007 08:37 pm
a) The causes of anovulatory infertility can be divided in to three main categories according to the level of disruption between hypothalamic - Pituitary - ovarian axis & ovary. Anovulation may be due to hypergonadotrophic - hypogonadism due to premature ovarian failure and resistant ovary syndrome as a result of failure of ovary to respond to gonodotrophins stimulation. Hypogonadotrophic hypogonadism occurs due to failure of pituitary gland to produce gonadotrophins. This includes causes like destruction of pituitary gland by tumor (Benign non functioning adenexa, craniocpharyngioma), tuberculosis, ischemia (Sheehan?s syndrome,) rare congenital causes like kallman?s syndrome and destruction of pituitary by surgery or irradiation. Hypothalamic dysfunction may result from excessive, weight loss psychological stress or anorexia nervosa when pulsatile secretion of GnRH is slowed or stops. The cause of anovulation may be due to ovarian dysfunction as seen in PCOS (normogonadotrophic anovulation). Lastly, endocrine disorders like hyperprolacteinamia and hypothyroidism may lead to anovulation leading to infertility. b) The investigations advised in this case are guided by history and clinical examination. A regular menstrual history is suggestive of ovulatery cycles and history of irregular cycles or amenorrhoea may point towards anovulation hence investigations advised include S. Progesterone level (> 30 mmd/L) is suggestive of ovulation. S. FSH/ LH & E2 on day 2 of cycle or withdrawal bleed if cycles are irregular should be done in all women to ascertain the cause of anovulation. A high FSH and levels LH points towards hyperganodotrophic hypoganodism and a low FSH and levels LH point towards hypogonadotrophic hypogonadism while an altered LH/FSH ratio >2 is an indicator of PCOS although this criteria is no longer used. A normal serum prolactin level excludes hyperprolacteinemia as a cause of anovulation, however slight elevation may be seen in PCOS. Pelvic USS should be requested in all women with PCOS showing characteristic morphology of arrangement of multiple follicles (> 10 in no. < 10 mm dia ) around central dense anechoic stroma. Karyotype should be advised in case of raised gonodotrophins (FSH>30IU/L) to diagnose. Turner?s syndrome if there are other stigmata presents. A serum prolactin level >1000 IU/L is indicative of prolactinoma and CT/ MRI of pituitary fossa should be advised to exclude pituitary tumour. Thyroid function tests should be advised if history is suggestive of thyroiddysfunction. c) The therapeutic options for anovulatory infertility depends on the cause of anovulation. First of all, normalization of body weight in underweight (BMI <19) and obese patients (BMI>29) can help to regain ovulation without medical intervention and dietician referred should be sought. Ovulation induction in PCOS women can be achieved by weight normalization (if obese), medical or surgical methods. The medical methods include use of clomiphene citrate, gonadotrophins and GnRH agonists. Clomiphene citrate should be given orally, started as 50 mg daily from day 2 of cycle for 5 days, results in ovulation in 80% cases and conception in 40% cases. Its use should be restricted to 6 months to avoid risk of ovarian cancer. Clomiphe use should be monitored developing with follicular tracking to detect the risk of OHSS and multiple pregnancy. Clomiphene resistant cases should be given gonadotrophins, its use need careful follicular tracking and may be associated with risks like OHSS & multiple pregnancy. GnRh use is restricted to women with anovulation due to clomiphene resistant cases and in cases or hypogonadotrophic hypoganodism. Laparoscopic ovarian drilling is a surgical option, should be used in clomiphene resistant women. It involves focal destruction of ovarian stroma with laser or diathermy associated with negligent risk of OHSS and multiple pregnancy and is less costly. The complications include injury to bladder, bowel and vessels, anesthetic risks and reduction of ovarian reserve. Medical treatment of prolactinoma with Cabergoline or Bromocriptine helps in regaining ovulation. The women with anovulatory infertility due to ovarian failure and resistant ovarian syndrome should be offered oocyte donation. Women with anovulatory infertility who fail to respond to ovulation indication with IUI should be offered IVF.
		Posted by Saad A. Fri Jul 20, 2007 01:31 am
Dear paul Please check my answer. Best regards
		Posted by AMNA K. Fri Jul 20, 2007 01:39 am
Dear paul donot forget to check my answer
		Posted by Natalie P C. Sat Jul 21, 2007 02:55 am
Answer A WHO classification of anovulation is as follows. Type 1 is hypothalamic ?pituatary failure where causes include stress, weight loss, Kallman syndrome, gonadotrophin deficiency. There are low gonadotrophin levels. Type 2 is hypothalamic ? pituitary dysfunction where gonadotrophin (Gn) levels are normal and the main cause is polycystic ovarian syndrome (PCOS). Type 3 is due to ovarian failure and causes include premature ovarian failure like Turner?s syndrome, Down?s syndrome, Idiopathic and 47 XXX syndrome. Estrogen is low and gonadotrophins are high. B I would calculate BMI and ask about recent weight loss. Excessive weight loss can cause type 1 and raised BMI is often seen in women with PCOS. I would do karyotype especially if clinically she has any syndromic features. I would do a hormone profile eastradiol , LH, FSH day 2 (which if high suggests ovarian failure).Male hormone levels including testosterone and androstedione may be high in PCOS. Levels of SHBG may also assist. A progesterone challenge test would produce no bleeding for women with type 1 and 3. Some women with type 2 would respond with a withdrawal bleed. Prolactin levels may be high so these can be done especially in women with galactorrhoea. C If a woman has type 2 PCOS then the least invasive method to help her is oral ovulation induction agents such as Clomiphine Citrate. Ovulation rate are 20-25% with pregnancy rate of up to 70% over 6 months. The drug is generally well tolerated with some patients having side effects such as nausea, hot flushes, mood swings. Ovarian hyperstimulation syndrome (OHSS) is quite uncommon and multiple pregnancy rates are 7%. She would need regular scanning for follicular tracking to assess her body?s response to the drug so the dose can be regulated to reduce OHSS and multiple pregnancies. Intrauterine insemination (IUI) with Gn stimulation can be offered if she has no success with clomiphene or if she has type 1. Success rates are 10-12% per cycle. This procedure is moderately invasive requiring collection and preparation of sperm before the IUI and as she is anovulatory she would require ovulation induction with all the attendant side effects. Use of Gn has higher multiple pregnancy and OHSS rates. Intrav fertilisation is the most invasive of the options. This is offered to type 1 and 2 women with failed IUI treatment or women with type 3 who accept egg donation. These women who have ovarian failure will not respond to ovulation induction and require egg donation. Eggs can be difficult to source and these women must be offered counselling. IVF success rates are the highest of the 3 options at 20-27% per cycle but also with the highest OHSS (20-30%) and multiple pregnancy (20%) rates. This is also the most invasive of the options require minor surgery for egg collection with it?s anaesthetic and surgical risks such as bleeding and infection.
		Posted by Sabahat S. Sat Jul 21, 2007 03:37 am
About 1 in six couples suffer from infertility. A) The likely cause could be obvious from a good relevant history. Duration of cohabitation or duration of having unprotected sexual intercourse is important. Previous H/O contraception, the method or the duration for which it was used should be elicited. Irregular menses with cycles of longer than 35 ? 40 days, (oligomenorrhora), obesity, amenorrhoea ( no menses since > 6 months ) , along with complaints of hirsutism, weight gain, acne, are indicative of polycystic ovary disease.Any breast secretions (in the absence of breast feeding ) indicate hyperprolactinaemia.There may be H/O headache, visual field defects in pituitary macroprolactinomas.A history of radiotherapy or chemotherapy may indicate pitutary failure ( in brain irradiations )or premature ovarian failure.History of viral illness (e.g Mumps ) could be a reason for premature ovarian failure which may be associated symptoms of hot flushes, decreased libido, vulvovaginal atropy ( recurrent UTI, superficial dyspareunia ). A history of meningitis, encephalitis, brain tumor, head trauma may be indicative of pituitary damage. History of weight loss, excessive / strenuous physical exercise, or stress could be the reason for hypothalamic dysfunction. A history of thyroid disorders, or symptoms of cold intolerance, constipation, dry skin, previous thyroid surgery, lethargy may indicate hypothyroidism. Any severe systemicillness like renal failure, uncontrolled IDDM, is important. History of diarrhoea, weight loss ,signs of malnutrition, e.g crohns disease could be present. A history of any previous child birth followed by severe PPH & failure of lactation may be indicative of sheehans syndrome. There could be obvious signs of short stature, low set hair line, broad shield like chest , with widely spread nipples, ill developed breasts, wide carrying angle to indicate Turners syndrome which is associated with premature ovarian failure. B) Serum FSH, LH ( may be high ) estrogen ( high ) testosterone ( normal or high along with sonological evidence of multiple ovarian follicles in the cortex issuggestive of PCOS. Serum prolactin levels (at rest, not under stress ) more than 400 gm/ml in hyperprolactinaemia . x-ray skull should be done to rule out a pituitary prolactinoma. MRI skull is done to delineate any space occupying lesion, compressing the pituitary or pituitary stalk. Serum TSH, LH, FSH, GH, prolactin, ACTH all may be low in Sheehans syndrome. High ACTH, low cortisol is indicative of Cushing disease. High serum cortical with low serum ACTH is present in Cushing syndrome ? TSH, T3 T4 should be done. High T3, T4 with low or normal TSH is indicative of hyperthyroidism where as low T3, T4 & high TSH is present in hypothyroidism. Laproscopic could be done delineate the ovarian morphology in PCOS,streak ovaries in Turner syndrome. Ovarian biopsy is rarely required to establish the diagnosis in premature ovarian failure or resistant ovary syndrome. Karyotyping is required in Turner syndrome to establish the diagnosis. C) Watchful expectancy, and not initiating any treatment is an option the couple have, depending on the severity of the condition. Many of the couples subsequently achieve pregnancy spontaneously by this method. In PCOS, weight reduction, dietary advice & moderate daily exercise, if applicable, is greatly helpful. Ovalution induction is done by clomiphene citrate, metformin, gonadotrophin & GnRHa. She should be councelled regarding the risk of OHSS (5- 10%) & regular foliculometry is therefore required. Laparoscopic ovarian drilling is equally effective in ovulation induction with the added advantage of not requiring follicle tracking, decreased risk of multiple gestation & OHSS. The requirement for GA is a disadvantage & it is an invasive procedure. Bromcriptine, is useful in hyperprolactinaemia.There, but side effects limit its efficacy (nausea, dizziness, hypotension ) & so it has to be started gradually with low dose at bed time & with meal. Cabergoline has a much tolerable side effect profile & less frequent ( twice weekly initially & then once weekly ) dosing. These drugs can be used along with clomiphene citrate for ovalution induction & treatment stopped when PT is positive. In case of hypothyroidism, thyroid hormone replacement is required in consultation with an endocrinologist . Attaining a enthyroid status is helpful in reestablishing regular ovulation. In case of anorexia nervosa, or Bulemia, supportive counselling in addition to advise regarding weight gain & maintaining a normal weight, stress reducing measures, cutting down on strenuous excessive exercise is helpful in recovery of normal ovulatory cycles. In malabsorbtion syndrome ( gluten enteropathy ) a gluten free diet, iron, foliate, B12 supplementation & treating malnutrition is helpful. Avoiding alcohol, smoking, and illicit recreational drugs is advantageous. Folic acid supplementation should be started. Control & stabilization of any chronic systemic conditions e.g. renal disease, uncontrolled IDDM should be done. Supplementation with pituitary hormones (FSH, LH, GH, ACTH) is required in-patient with hypopitutarism (Sheehan?s syndrome). In Turner syndrome, donor Acolyte with IVF & embryo transfer is an option. In resistant ovary syndrome retrieval of her Acolytes (to enable genetic parenthood of their off spring) with IVF embryo transfer could be done, in case all such treatments fail the couple should be counseled regarding the option of adoption. Psychological support & supportive counseling at all stages is integral to the management of an infertile couple.
		Posted by AMNA K. Sat Jul 21, 2007 06:29 pm
Dear paul Thanks for marking my answer.
		Posted by Saad A. Sat Jul 21, 2007 08:41 pm
THANKS FOR EVALUATING MY ANSWER. REGARDS