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Essay 339 - Sub-fertility

Posted by Aruna R.
A healthy 30 year old woman with a 2 year history of irregular periods has been referred to the fertility clinic because of primary infertility. Investigations show FSH= 54 iu/l, LH=35 iu/l. What will you tell her about the possible causes of her condition? [5 marks]. Discuss the additional investigations that you will undertake [5 marks]. Discuss your subsequent management given that no underlying cause is found [10 marks]

Aruna

The probable diagnosis is premature ovarian failure. The causes are idiopathic , autoimmune, infection like mumps, Chemotherapy and radiotherapy .Genetic coonditions like turner, fragile X syndrome can cause premature ovarian failure.

The investigations include serum estradiole, DEHA-S,DEAH, testostrone, and prolactin level. Thyroid stimulating antibody, antiperoxidase antiboby ,anti androgen antibody and blood sugar levels to find out the autoimmune disease causing polyendocrinopathies.Karyotyping to find out turner, fragile Xsyndrome.Ultrasound(trans abdominal or transvaginal) to find out polycystic ovary syndrome.It is also essential to do prenancy test.
Ovarian biopsy is not necessary for resistant ovary syndrome. In adition to this partner\'s seminal analysis is essential.

Management:
History : in adition to infertility , does she have any other symptoms like hotflushes, sweating ,dryness in the vagina.
since the question said the cause is idiopathic i would not ask other details.
I will explain the diagnosis to the couple and its implications like premature menopause,subfertility and osteoporosis.Spontaneou conception is a possibilitybut it is very rare. the other options are ovum donation or adoption.
The couple should be treated with sympathy and support.Multidisciplanary aproach including counsellors, obstetrician, and endocrinologist .HRT is required after delivery to prevent the symptoms if any.
Written information about the condition and the support group web address are given to her.
Full documentation of the consultation in her notes.
Posted by S P.
sensitively explain the probable diagnosis is premature ovarian failure- the ovaries have had an accelerated follicular atresia. this could be idiopathic as seen in most cases.it could be due to chromosomal anomalies [ turners /fragile x ]. infections - mumps , tuberculosis .autoimmune disorders -associated with other autoimmune conditions such as thyroid disease, pernicious anaemia.metabolic defects - galactosemia . enzyme deficiency-congenital adrenal hyperplasia.could be iatrogenic due to surgical removal or radiotherapy. there is possibility of resistant ovarian syndrome , this clinically indistinguishable , only diferenciated by ovarian biopsy , however confirming it does not alter her management of infertility
BI would do a pregnancy test to .Estradiol level[ can be normal as rarely sporadic ovulation occurs ] , DHEAS, DHEA , Prolactin , 17 OH progesterone[ to r/o CAH}. TSH, antithyroid peroxidase antibody . Anti adrenal antibodies , ChromOsomal analysis .Test of fragile x chromosome . A semen analysis of the partner.
C Take h/o of any associated symptoms of hot flushes , night sweats , vaginal dryness. WIll explain the implications of her condition. POF will lead to premature menopause associated with increased risk of cardiovascular disease , osteoporosis . Although sporadic ovulation does occur it is rare . She has an option of an IVF pregnancy with donor oocyte and partner semen . sucess rates in women with POF being same as age related success rates. Would explain all oocyte donors are pre screened for genetic diseases and infection {as per HEFA ] .Written information to be given Alternatively She can choose no further treatment and adoption . If menopausal symptoms are affecting her OAL ,she can be offered HRT after concelling and about all the benefits and adverse affects Written information of POF to be given . Contacts of supports groups to be given.
Posted by Mohamed D.
Mohamed
What will you tell her about the possible causes of her condition? [5 marks].
Most probably this is a premature ovarian failure or resistant ovary syndrome. The most common cause is idiopathic where no cause will be found. There is a possibility that this could be due to auto immune disease with autoimmune destruction of other organs as the thyroid in Hashimoto’s thyroiditis and adrenal gland in Addison’s disease. Genetic condition is a possibility as mosaic Turner syndrome, and fragile X syndrome. Infection with mumps is another possibility which will induce autoimmune destruction of ovarian tissue.

Discuss the additional investigations that you will undertake [5 marks].
Repeat FSH and LH again for confirmation of diagnosis. Check her inhibin levels as it is more accurate in diagnosis of ovarian failure. Pregnancy test should be checked as she may be pregnant. Serum estradiol need to be evaluated and it may be normal as sporadic ovulation still can occur, but mostly will be low. Karryotyping to find if she had a genetic condition as mosaic Turner or fragile X syndrome. Autoimmune antibodies as thyroid antibodies can be checked. Pelvic ultrasound would find out if she had streak gonads, PCO, or pelvic mass. The partner semen analysis should be checked for plan of their fertility treatment.

Discuss your subsequent management given that no underlying cause is found [10 marks]
In regard to her fertility, she may get spontaneous pregnancy in 5-10% of the cases because of sporadic ovulation still can occur. Treatment options include egg donation and fertilisation with partner’s semen in IVF. Pregnancy rate is good for her age. The other option is adoption, but she should be advised about the long process and waiting time for that.
If she is suffering any menopausal symptoms like hot flushes, or vaginal dryness, she should be counselled about treatment risks and benefits. Diet and exercise should be tries first. Clonidine or SERMs is another options for her symptoms. Vaginal dryness should be treated with lubricants and local oestrogen pessaries. She should advised about the risks of osteoporosis and heart ischemic diseases with early menopause. HRT is good in preserving her bone density and doe not increase her risk of breast cancer if taken till the age of natural menopause. Other wise she can try biphosphonates or tibolone. Treatment of any other organ failure as thyroid or adrenal to optimize her health.
She should have written information about her condition and implications on her health. She should have information about support groups like the international premature ovarian failure association (pofsupport). Her management should be under multi-disciplinary care and her GP should be informed about the condition and management plans.
Posted by A A.
AA (KSA)
a) I would sensitively explain the most probable cause is premature ovarian failure(POF) . POF is of Unknown etiology in most cases (~50%). It could be due to chromosomal abnormalities ( 45X ,47XXY , fragile X syndrome, structural abnormalities of sex chromosomes), Auto-immune disorder like thyroid disease , Addison’s disease ,pernicious anaemia .Viral Infections like mumps .In healthy woman iatrogenic causes like bilateral oophorectomy, Irradiation / chemotherapy are excluded. I would like to repeat the FSH/LH levels to exclude laboratory error or mid luteal high levels of these hormones.
B)
• Repeat FSH, LH to confirm diagnosis. Pregnancy test to exclude pregnancy . Estradiol , androgens, DHEA, DHEA-S to check any associated hormonal disturbance. Serum prolactin to rule out hyper prolactinemia. Abdominal & TVS for steak ovary or any other pelvic pathology. Karyotype for chromosomal abnormalities .TSH & auto immune screen for thyroid & adrenal antibodies. Blood Glucose for diabetes. Bone density scan to estimate bone mineral density as there is risk of osteoporsis. Ovarian biopsy not indicated. Partner semen analysis if not already performed .

•C) Inform her the diagnosis of early menopause in a sympathetic manner. Offer sensitive counseling ,information leaflets & support group information (DAISY NETWORK).Regarding her fertiliy concern ,one option for her is donar egg (after appropriate counseling ) with IVF-ET. The success rate is equivalent to conventional IVF .She may opt to wait for spontaneous conception as spontaneous ovulation and pregnancy may still occur. Other options are straight surrogacy or adoptions which have legal & ethical implications . I would provide her support group detail about surrogacy ( COTS)& appropiate referral. I would explain the impact of early menopause.She would need long term HRT ( Estrogen with cyclical progesterone) until 52 years to protect against osteoporesis , vasomotor symptoms& CVS risks. HRT will not increase her risk of breast cancer till age of natural menopause. Androgen levels may be low , consider testosterone patch if she complains of decreased libido .Routinely not recomended.I would provide her appropriate advice about diet & lifestyle modification.Inquire about her concerns & wishes.Provide follow-up to ensure adequacy of HRT and annual bone densitometry.
Posted by Ir A.
A healthy 30 year old woman with a 2 year history of irregular periods has been referred to the fertility clinic because of primary infertility. Investigations show FSH= 54 iu/l, LH=35 iu/l. What will you tell her about the possible causes of her condition? [5 marks]. Discuss the additional investigations that you will undertake [5 marks]. Discuss your subsequent management given that no underlying cause is found [10 marks]

If
a)I will explain to her that the history and investigations are suggestive of premature ovarian failure. The underlying eitiology is unexplained in most cases. 30 to 40% cases may be secondary to genetic abnormalities, the most common being turner\'s syndrome. Other karyotypic abnormalities and fragile X syndrome may also cause premature ovarian failure. It may have autoimmune etilogy. Infections like mumps can also cause premature ovarian failure.

b) I would like to repeat the serum FSH and LH and also do serum estradiol. I will order serum prolactin, thyroid stimulating hormone and antithyroid antibodies. Serum androgens, DHEA (dehydroxyepiandrostenedione), DHEAS and beta hydroxy progesterone should be measured. A transvaginal scan is done to rule out polycystic ovaries or genital tract anomalies. a karyotype should be done. A baseline bone densitometry should be done. Measurement of antimullerian hormone (AMH) will help in predicting ovarian reserve and may be useful as this patient wants to conceive.

c) The diagnosis is bound to cause significant anxiety and distress. The patient and her partner should be dealt with in an empathic manner and should be counselled and provided with written information and given contact numbers of support groups.
If no underlying pathology is found, spontaneous ovulation may resume in 20% patients and spontaneous conception may occur. However, keeping in view the age of the patient, 2 year history of infertility and raised FSH/LH values, she should be offered in vitro fertilization (IVF) with oocyte donation. The issue needs to be addressed sensitively and will need input from counsellors and medical workers in the subfertility team dealing with these issues. She should be screened for hepatitis B, hepatitis C and HIV. Her partner\'s semen analysis should be done.
If she does not wish to undergo IVF, adoption may be another option.
Lifestyle advice regarding smoking cessation, decreasing alcohol intake and exercise should be given. The long term risks of premature ovarian failure of osteoporosis and cardiovascular disease should be explained to her. The use of hormone replacement therapy (HRT) for osteoprotection should be discussed. If she opts for adoption, combined oral contraceptives may be prescribed as HRT.
Posted by Im F.
a) The probable cause of her infertility seems to be premature ovarian failure (POF) which is very rare in this age group. She should be approached sensitively to explain the causes. She should be told that in most cases there is no cause (idiopathic). It can be related to chromosomal defects (abnormal karyotype) like 45 X (Turner’s syndrome) or 47 XXY followed by mosaicism. There can be structural defects in sex chromosomes like Fragile ‘X’ syndrome. She should be told that it can be due to some autoimmune disorder in some cases and associated with increased risk of other autoimmune diseases like thyroid or pernicious anaemia. It might be related to mumps leading to infection of ovaries. If she had chemotherapy or radiotherapy in past, it can also result in POF. She might have a resistant ovary syndrome.

b) We should investigate her to find cause of POF. Her FSH and LH have already been done. We can do her serum estradiol level which can be normal as sometimes spontaneous ovulation may occur. Serum prolactin, androgens, DHEA, DHEAS and 21 OH progesterone should be done to see the status of hormones. Thyroid stimulating hormone (TSH), antithyroid antibody and serum adrenal antibodies should also be done to rule out autoimmune thyroiditis. A karyotype should be done to find any chromosomal defect like Turner’s and fragile X syndrome. Her bone density scan should be done to assess osteoporosis. A transvaginal scan to assess follicle size can reassure patient but unlikely to give much information. Ovarian biopsy can also be done to rule out resistant ovary syndrome. Finally, semen analysis should also be conducted in order to find male factor infertility so that future planning can be done.

c) There should be a sensitive approach. She should be informed of diagnosis, nature of disease and its implications like premature menopause, osteoporosis and cardiovascular risk. Preferably counseling should be done in presence of partner if she agrees. She should be informed about patient support groups. She should be reassured that sometimes spontaneous ovulation and pregnancy may occur in 20% of patient. Women’s needs should be identified first. She should be asked about menopausal symptoms like hot flushes, night sweats, anxiety, loss of libido, insomnia and irritability and her concern about it whether she needs treatment like HRT or not. As she is keen for pregnancy and under follow up of infertility clinic, so HRT/COCP is not advisable until after diagnosis she changes her mind.
As no underlying cause is found in her case, she should be given option of IVF with oocyte donation. She should be explained that oocyte donation is a procedure in which oocyte from some other female will be fertilized with her partners’ sperm (provided his semen analysis is normal). All the ethical issues (like not having her own genetic child) related to it and protocol as per HFEA should be explained to her. Success rate of oocyte donation should be informed to her. She should be given written information about this procedure. Next option is adoption but it has its own disadvantages like not being the genetic child of couple and sometimes it is time consuming. Last option is wait and see policy for spontaneous ovulation. Vitamin D and calcium should be given to her for bone protection. She should be followed up with DEXA scans. Finally, she should be given information about POF and support groups.


Posted by Chitra.s M.
A.A sensitive approach is adopted.The woman is informed that premature ovarian failure is the most likely diagnosis.This could be due to be due to chromosomal abnormalities like turner\'s mosaic and fragile X syndrome.Premature ovarian failure can be due to an autoimmune cause and may be associated with other autoimmune conditions like diabetes,hypothyroidsm and pernicious anaemia .Infections like mumps may be the cause.It could also be due to resistant ovary syndrome where the follicles are unresponsive to gonadotrophins.However no cause may be found as it may be idiopathic.Written information is provided.
B.Investigations include karyotyping for detection of chromosomal abnormalities like Turner\'s and fragileX syndrome.Thyroid function tests are done for evidence of associated hypothyroidism. Blood sugar estimation is done to look for diabetes mellitus.FSH,LH levels are rechecked for confirmation.Urine pregnancy test is done to rule out pregnancy.Abdomino-pelvic ultrasound scan is done for any pathology .Ovarian biopsy for diagnosis of the cause is not required as the management is not altered.Partner\'s semen analysis is done if not performed previously.
C.The woman is enquired about menopausal symptoms like hot flushes, night sweats and vaginal dryness.She is informed that although spontaneous ovulation and pregnancy may occur, it is rare.Her options for fertility treatment include IVF pregnancy with ovum donation. Adoption is another option.
She is counselled that hormone replacement therapy is required for relief of hot flushes and urogenital symptoms and for long term bone and cardiovascular protection.HRT continued till the age of natural menopause(50 years) is not associated with increased risk of breast cancer.The different options for HRT-combined oral contraceptive pills, oral conjugated estrogen and progestogen and estrogen patches/implants with LNG IUS for endometrial protection is discussed. Advice is given about life style modification like cessation of smoking,maintenance of healthy BMI and aerobic exercises to help prevent bone density loss.She is informed about the increased chances of developing other autoimmune conditions like diabetes,hypothyroidism and pernicious anaemia.Annual screening for diabetes and thyroid function is required.Regular bone mineral density measurement is required to detect bone density loss.
The discussion and the woman\'s views on fertility options and HRT are documented.Written information and details of support groups like POF support group provided.
Posted by Syamala H.
syamalah
ans a: high levels of gonadotropins are suggestive of the fact that ovaries are not responding to its stimulation. the possible diagnosis is of premature ovarian failure or resistant ovary syndrome.it not prudent to make a firm diagnosis on single measurement due to intercycle variabilty in FSH, and repeat testing( preferrably during follicular phase )would be required .there are two issues involved with this diagnosis, first is subfertility and the fact that she will not ovulate after gonadotropin stimulation for an IVF and is left with the option of oocyte donation, complete surrogacy or adoption. the second issue is hypoestrogenemia due to ovarian failure will have long term consequenses on her health and she is at increased risk of cardiovascular disease and osteoporosis. possible causes for her condition are chromosomal abnormality, auto immune destruction or condition like galactosemia, viral infection like mumps or prevoius chemo or radiotherapy. majority of cases cause remains unknown. possibilty of spontaneous conception in 10-20% if karyotype normal. this diagnosis is associated with anxiety and apprehension and she should have counselling by dedicated fertility counseller.
ans b:
additional investigation will include repeating gonadotropin level and serum estradiol. also she can be tested for serum inhibin and antimullerian harmone along with TVS for antral follicle count and ovarian volume for ovarian reserve testing. but ideal test for ovarian reserve that is useful clinically is a matter of debate.
she required testing for karyotype as 40% of premature ovarian failure(POF) are associated with chromosomal abnormality like 45XO or 47 XXY or mosiacism or partial deletion of sex chromosome. also seen in families with fragile x syndrome. testing for antibodies to daignose other autoimmune condition like thyriod disorders pernicious anemia and diabeties.serum prolactin and MRI/CT brain to rule out craniopharyngioma.testing 17 alpha hydroxylase deficiency by measuring serum progesterone, 17 alpha hydroxypregesterone and deoxy corticosterone and confirmed by ACTH stimulation test.semen testing as spontaneous conception still a possibilty in few patients.ovarian biopsy not recommended. DEXA scan for assesment of osteoporosis.
ansc:
managment has to be multideciplinary involving fertility specialist, endocrinologist, counseller and social worker. options for mangment for subferlity are oocyte donation and IVF, surrogacy and adoption. regarding oocyte donation and IVF she should be told about the cost involved and it may not be covered by NHS. also the success rate ranges from 20-30% .disadvantage is of having a child not genetically related to her. second option is surrogacy where a surrogate mother is inseminated with partner semen.legal implications should be explained. in case of adoption involment of social worker would be required and there can be long waiting period. child will be genetically unrelated. she can opt for no treatment. rarely spontaneous conception can occur.
if patient has menopausal symptom treatment is directed for their relief. she would require HRT till the age of menopause.also annual screening for bone loss by DEXA.Life style modification, exercise and stopping smoking calcium and vit D to aviod accelerated bone loss. screening for hyperlipidemia, hypertension diabetes and thyriod disorder would be required annually she is high risk for these diseases .provide written information and support group.
Posted by H H.
H
A healthy 30 year old woman with a 2 year history of irregular periods has been referred to the fertility clinic because of primary infertility. Investigations show FSH= 54 iu/l, LH=35 iu/l. What will you tell her about the possible causes of her condition? [5 marks
I will tell her that her brain hormones (FSH,LH) are high and this means that her ovaries are not functioning well. This can be due to premature ovarian failure POF (ovaries fail to ovulate ,or produce hormones) which at her age occur in 1/1000 women. However, those hormones might be elevated due to another condition called resistant ovary syndrome in which the ovaries do not respond to the high hormone signal from her brain. As she is healthy, her ovarian failure is unlikely to be due to exposure to radiotherapy or chemotherapy, but may be due to chromosomal or auto immune disease not diagnosed and star to present with this condition.
I will tell her that I will need to repeat the test (FSH,LH) , as this might have been measured at the time of ovulation at which these hormones are elevated, though this possibility is unlikely as the patient has irregular period.



Discuss the additional investigations that you will undertake [5 marks
I will repeate serum FSH and LH to see if they are persistantly elevated. Will ask for serum estradiol level which expected to be low in menopausal range.Will check by transvaginal ultrasound TVUS for any growing follicles in the ovaries, these can be monitored for growth by repeated TVUS. Will ask for tests that might detect the cause which is not apprent as shee is healthy ,karyotyping for chromosomal abnormalities such as turner mosiac, fragile X syndrome , autoimmune screen ( thyroid, diabetes, pernicious anemia) .
Will ask for bone density scan as a baseline scan to be compared with subsequent scans. Will ask for serum cholestrole and triglycerides which are elevated in POF. Will ask of semen analysis for her partner to see if he also has a problem.

Discuss your subsequent management given that no underlying cause is found [10 marks]
Patient is sensitvely counselled regarding her condition as it is a hard subject to bring to this lady who is in her early thirties and is seeking to have a baby. I will tell her that she can opt to bring her partner during the discussion. I will tell her that the chances of getting pregnant naturally are near nil, though pregnancies were reported from sporadic ovulation occured. Will tell her she can get pregnant through egg donation,but this would include in vitro fertilisation and embryo transfere and might be costy. She and her partner can adopt a child ,but will need long time of paper work and patience.Patient wishes are respected.
As she has low estrogen levels in the menopausal range, there is risk of osteoporosis and cardiovascular disease , these will be raised in my discussion with the patient. She will need hormone replacement therapy HRT until she is 50 years old. We are replacing her normal level which she would have had if she has not had this problem. Risks of HRT ( breast cancer, increased cardiovascular disease, venous thromboembolism) were shown by studies done in women over 50 and not in these cases. Multidisciplinary in put is needed in treatment including gynecologist, psychiatrist (if patient goes into depression), physician and social worker.
Patient will be followed by yearly bone scans and monitoring of her serum lipids. She is adviced of healthy life style,excersis,diet, stop smoking and alcohol.
Patient given written information about her case and advised to contact support groups which offer the chance of meeting with similar cases and describe acclimitisation with life.
Posted by shahana M.
Primary infertility is distressing to both the couple.eventhough I know that she is having hypergonadotrophic hypogonadismfrom her elevated FSH,and LH and its success rate is limited when compared to unexplained infertility,I would support her ad reassure thather problem needs to be evaluated and treatment can be decided after words after reconfirming the hormonal profile(FSH,LH,Testosterone,Oestradiol, SHBG-which can be abnormal) if possible on day2 of cycle .I would like to get more information from her like,any history of mumps, chemotherapy,radiotherapy,bilateral oohorectomy for torsion,malignancy in the child hood,any auto immune dieaseeven though shi is healthy , family history of similar conditionas all of these are associated with Premature ovarian failure,a cuase for hypergonadotropism.i would ask regarding her menstrual periods again as some patients may lie that they are getting periods evethough pimary amenorrhoea especially oronly withdrawal bleeding with progesterone in case of androgen insensitivity syndrome and pure gonadl dysgenesis or turners syndrome .respectively,Another cause could be ovarian resistant syndrome in which auto antibodies produced against gonadotrophin receptors prevent ovaries to respond on elevated gonadotrophin.i would offer physical examination to find out the possible causesand to decide upon the investigation.
B.The additional investigation apart from repeatedFSH,LH, i w uold like to have testosterone(reduced in premature ovarian failure and turners and pure gonadol dysplasia and normal male level in androgen insensitivity syndrome)oestradiol which is reduced in all these condition.i also will suggest karyotyping to know the chromosomal abnormalities 45x for turner syndrome along with physical examination finding like short stature, webbing of neck, widely spaced nipple), 46xy in androgen insensitivity syndrome(normal or tall height, good breast development, absent pubic or axillary hair) and pure gonadal dysplasia with no poor breast development,mild to mod pubic or axillary hair and trans vaginal +/-trans abdominal ultrasound to look for uterus , size, endometrial thickness,ovaries its presence and size and follicle.uterus and ovaries will be reduced in size with thin endometrium less than 5mm in turners , premature ovarian failure,pure gonadal dysgenesis and they will be absent in androgen insensitivity syndrome with testes in labia or inguinal canal or in the abdominal cavity found out in trans abdominal USG.I will also refer to physician if she is giving history of galactossemia which is seen associated with premature ovarian failure for furthe r management in case responded well mayhelp in conception.
C.if no underlying cause found the cause may be premature ovarian failure due to idiopathic reasons.i will disclose it in a sensitive and supportive manner that no undrlying cuse have been found out , it happens with premaur eovarian failure .It will not affect her health excpt the osteoporosis ,sexual dyspareunia which can be reduced with active intervention like Hormonal replacement therapy after explaining its side effects.regarding conception there is a rare possibility of spontaneous ovulation and conception in which she can have her biological baby,or by donor oocyte ,in vitro fertilisation and embryo transfer and Homonal replacement therapy .The last option is adoption. To prevent osteoporosis hormonal replacement therapy , healthy lifestyle practices like regular exercise, diet restriction if obese,quiting or reducinn smoking, alcohol advised after giving contact address of support gruops and written leaflets regarding premature ovarian failures ,effects on health. and infertility. options with arranging another appointment with consultant
Posted by sonu P.
a)I will tell her the diagnosis of premature ovarian failure sensitively and acknowledge the distress such diagnosis will cause to her. The most common cause of this is idiopathic. Other possible causes are childhood mumps infection, undiagnosed autoimmune conditions, turner’s syndrome or turner mosaic, ovarian dysgenesis, resistant ovary syndrome.

B) I will request a pelvic ultrasound to assess the development of other reproductive organs. Thyroid function test and a fasting blood sugar may suggest an autoimmune component of the diagnosis. I will also request a blood karyotype study especially if there are other phenotypic stigmata of turner’s syndrome like short stature, webbed neck and increased carrying angle. A serum prolactin level and MRI cranium will help to rule out central causes of raised gonadotrophin levels.

c) This diagnosis is associated with a lot of anxiety and distress in patients especially who are trying to conceive. They should be dealt in an empathetic and professional manner. The mainstay of treatment for idiopathic premature ovarian failure is ovum donation and IVF. The possibility of adoption should also be discussed. The legal and ethical issues of ovum donation and adoption should be discussed at a later date with the fertility expert. The patient along with her partner should be given the opportunity to be counseled by a reproductive medicine specialist preferably in a tertiary fertility center. While they are waiting for the appointment from fertility center, support should be provided by a named nurse by locally agreed guidelines. The other issues to consider is hormone replacement treatment in future to decrease the chances of acute and long term consequences of premature ovarian failure like hot flushes,mood swings, psychological issues, vaginal dryness/dyspareunia, cardiovascular disease, osteoporosis etc. The provision of written information and contact details of self help and support groups is invaluable in this situation when patient might not be able to assimilate all the information given in the first consultation.A follow up appointment should be considered on patients request.

Posted by SARO K.
Hormonal profile points to the diagnosis of Premature Ovarian Failure.
Causes:
1.Idiopathic-Most common
2.Genetic/Chromosomal-Turners syndrome,Fragile X syndrome
3.Infection -Mumps
4.Resistant ovary syndrome
5.Chemotherapy,Radiotherapy,surgical
6.Autoimmune - associated with Diabetes,pernicious anemia and hypothyroidism.
7.Galactosemia.

Investigations:
1.Repeat FSH,LH.
2.Serum estradiol
3.Urine pregnancy test to rule out pregnancy.
4.Blood sugar to rule out diabetes
5.serum cholesterol,triglycerides as it is raised in premature ovarian failure.
6.Thyroid function test -TSH and Antithyroid antibodies.
7.TAS/TVS - to see the antral follicles and ovarian volume.
8.Karyotype is offered-turner mosaics.
9.As part of work up of infertile couple,I will offer Husband semen analysis to rule out male factor infertility.
10.DEXA to have baseline bone density for further follow up.
Management:
Sensitive approach to the patient.
Multidisciplinary team includes -gynecologist ,endocrinologist,infertility specialist,midwife,social worker and support group.
Reasurance- chance of spontaneous ovualtion and pregnancy is possible but very rare 1-2%.
Options for infertilty/subfertilty-a.In Vitro fertilisation with donor ovum as they wont respond to gonadotropin stimulation success rate similar tthe age. b.Adoption c.Surrogacy .
Implications of POF:
1.Symptoms of hypoestrogenemia History should include Hot flushes,urogenital symptoms
2.osteoporosis
3.cardiovascular effects-Ischemic heart disease
4.Psychological:depression,anxiety,sleeplessnees
Treatment : includes
1.Lifestyle modification -cessation of smoking,exercise,maintenance of appropriate BMI,Walking,avoidance of alcoholandpractice of meditation and yoga.
2.reinforce that rare chance of spontaneous ovualtion and pregnancy.
3.HRT-COC Pills,oral CEE,Progestogen,Oestogens patches/implants,
LNG-IUS.
4.prevention and treatment of osteoporosis-calcium supplementation,bisphospanates.
5.treat associated medical conditions if found during work up -DM ,hypertriglyceridemia.
6.support group should be offered.
7.Further follow up for routine surveillance should be informed.
Posted by F N.
healthy 30 year old woman with a 2 year history of irregular periods has been referred to the fertility clinic because of primary infertility. Investigations show FSH= 54 iu/l, LH=35 iu/l. What will you tell her about the possible causes of her condition? [5 marks]. Discuss the additional investigations that you will undertake [5 marks]. Discuss your subsequent management given that no underlying cause is found. 10 marks

The diagnosis in her case can be premature ovarian failure (POF),however it needs to be confirmed by taking a detailed history and also the FSH levels needs to be repeated if its not done already.
The possible causes of POF Can be:
Genetic/chromosomal causes: Therefore family history of premature menopause is important,turner syndrome or fragile X chromosome can present with POF as well.Galactosemia and CAH (autosomal recessive) has been associated with POF.
chemotherapy/radiotherapy can cause POF.
POF has been associated with autoimmune disorders like SLE,rhumatoid arteritis,cushing syndrome,pernicious anemia,hypothrodisim and diabetes mellitis.
History of viral infection like mumps and CMV may be assciated with POF.
smoking and excessive alcohol intake may be responsile for POF.
There can be no cause identified in most cases and it can be idiopathic.

B:The harmonal profile needs to be repated,sustained levels of FSH more than 40iu/l can be suggestive of POF.Estadiol levels can be checked,low levels may be suggestive of POF.
antimullarian harmone (AMH) can be requested to confirm the diagnosis.
karyotype can be rquested to determine the genetic cause.
Thyroid function tests and tests for other auto mmune disorders may be requested if history is suggestive of it.
There is no role for doing antiovarian antibodies or ovarian biobsy as it does not change the management of POF.
role of pelvic USS in the diagnosis of POF is limited.

C:
She should be managed sensitively and with great empathy.she will need detailed counselling and psychological support to come to terms with the diagnosis of POF.Therefore a multidiscliplinary team comprising of her GP,gynaecologist,counseller,psychiatrist annd fertility specialist may be involved in her care.
she needs to be aware that she can ovulate spontaneously and there is a chance of spontaneous pregnancy,however the chances are low and egg donation may be needed to achieve a pregnancy.
She should be made aware of the longterm risks of osteoporosis and cardiovascular problems.she will need to use some form of HRT preferably till the age of natural menopause which is between 50-52 yrs in UK.All avaialble form of HRT with information leaflets should be discussed.
Advise on healthy life style modification like smoking,alcohol and exercise should be given.Information on support groups should be provided.
She need to use adequate contraception atleast for 1-2 yrs if not trying for a baby as can ovulate spontaneously.
Posted by Bee N.
A healthy 30 year old woman with a 2 year history of irregular periods has been referred to the fertility clinic because of primary infertility. Investigations show FSH= 54 iu/l, LH=35 iu/l. What will you tell her about the possible causes of her condition? [5 marks]. Discuss the additional investigations that you will undertake [5 marks]. Discuss your subsequent management given that no underlying cause is found [10 marks]


(bee)
A)I will tell her she most likely has premature ovarian failure and its mostly idiopathic. However it can be associated with certain chromosomal anomaly such as Turners syndrome 45XO and mosaics of 47XXY. It is also possible to be of autoimmune origin and can be suspected especially if she has other autoimmune diseases. It can also be caused by Mump virus infection. Treatment with radiotherapy or chemotherapy is also another cause.

B)Additional investigations I will undertake will be to rule out possible causes. I will do an autoimmune screening checking for antiphospholipid antibodies associated with SLE, antithyroid antobodies associted with thyroids disease and antiadrenal antobodies which may be a cause of addison\'s disease.. I will offer her karyotype to check for presence of chromosomal abnormality. I will also carry out tests that will help rule out other endocrine causes of anovulation such as DHEA, DHEA-S and testosterone and 17-OH progesterone which will be deranged in congenital adrenal hyperplasia. I will also want to check for prolactin level in case of hyperprolactinaemia and throid function test to rule out thyroid disease. I will want to do serology for IgG and IgM antibodies against mump virus to check for past or recent infection. I will also want to carry out seminal fluid analysis to rule out male factor contribution to infertility and help decide which option of management is available to her and her partner.

C) If no cause is found I will approach this patient is a sensitive and sympathetic manner. I will discuss management jointly with her and her partner. I will inform her that in cases that are idiopathic, their is 20% chance of spontaneous ovulation. I will tell her one option of management is to do nothing and wait for this to occur but timing of resumption is unpredictable. I will explain that if she however want to go on with assisted conception, the option is to have an egg donor with IVF. I will discuss the increase morbidity associated with IVF. This will enable her to carry the pregnancy which is not biologically hers. I will tell other option will be traditional surrogacy which allows another woman to carry the pregnancy which has been fertilised by her husband/partner by artificial insemination.I will tell her that this arrangement can be undertaken with the surrogate mother with the understanding that the child will be handed over to her a couple of weeks after birth The last will be adoption which allows them to raise and care for a child which as no biological relationship with her or her partner. this choice can be protracted in securing. The process and implications of these treatments will be discussed in further when she has signified the possible options she wishes to consider. This will help her make an informed choice. She is better managed under a multidisciplinary setting of an infertility specialist, gynaecology, general practioner, social worker and possibly psychiatrist if she finds the whole event too stressful. All discussions must be properly documented. She will be informed on long term consequences of premature ovarian failure such as osteoporosis and need to do a baseline dexa bone scan sometime in the near future (after her problem with infertility has been sorted). I will also inform her of her cardiovascular risk as need to embark on HRT after infertility has been managed.
Posted by L S.
LS:
a) What will you tell her about the possible causes of her condition? [5 marks].
Based on her blood test the most likely diagnosis is premature ovarian failure. I will tell her sensitively about the possibility that her ovaries might have undergone premature failure and that she is likely to have early menopause. This can be very upsetting to her as she has come for investigation for infertility and has not had children yet and should be offered psychological support during counselling. Often no cause is found but other conditions which can cause this should be investigated like chromosomal abnormalities (Down syndrome, Fragile X, Turner’s syndrome). Autoimmune diseases also can cause this for example hypothyroidism, Addison’s disease or diabetes mellitus. Enzyme deficiency conditions like galactosaemia can also be a cause. Since she has been previously healthy secondary causes like infective causes tuberculosis, mumps; post chemotherapy or radiotherapy induced or after surgery for bilateral oophorectomy can be ruled out.

b) Discuss the additional investigations that you will undertake [5 marks].
I will carry out a pregnancy test as she has irregular menses based on her last menstrual period date. Chromosomal analysis for karyotyping is performed. Autoimmune disorder test for poly endocrinopathy, thyroid function test and fasting blood sugar are carried out. If there is suspicion of Addison’s adrenocortocotrophic hormone stimulation test is performed. Bone density scan to estimate bone mineral density

c) Discuss your subsequent management given that no underlying cause is found [10 marks]
She should be adequately and sensitively counselled about her condition. The diagnosis , nature of disease and support group like the Diasy Network should be informed from the very beginning of her care so that she can have adequate psychological support. She should be informed that although often infertile, there can still be spontaneous ovarian activity which can result in unscheduled bleeding, menstruation or even pregnancy. Her needs should be addressed which will include fertility and management of menopausal symptoms. She will need long term hormone replacement therapy (estrogen with cyclical progestogen) until the age of 50. The dose of estrogen increased depending on her vasomotor symptoms. Combined oral contraceptive pills are also an option instead of HRT as some prefer it because of their peers uses it. She should be reassured that there is no increase in risk of breast cancer in taking HRT until the average age of menopauseand that it is mainly to control her vasomotor symptoms and to protect against osteoporosis. If she has reduced libido with or without persistent tiredness, she mat benefit from testosterone implant or patch. For her fertility, donor oocyte IVF is the best option if she desires pregnancy. The success rate is equivalent to that of others who undergo conventional IVF. She should be informed that the success is determined by the age of the donated oocyte rather than her age.
Posted by L S.
LS:
a) What will you tell her about the possible causes of her condition? [5 marks].
Based on her blood test the most likely diagnosis is premature ovarian failure. I will tell her sensitively about the possibility that her ovaries might have undergone premature failure and that she is likely to have early menopause. This can be very upsetting to her as she has come for investigation for infertility and has not had children yet and should be offered psychological support during counselling. Often no cause is found but other conditions which can cause this should be investigated like chromosomal abnormalities (Down syndrome, Fragile X, Turner’s syndrome). Autoimmune diseases also can cause this for example hypothyroidism, Addison’s disease or diabetes mellitus. Enzyme deficiency conditions like galactosaemia can also be a cause. Since she has been previously healthy secondary causes like infective causes tuberculosis, mumps; post chemotherapy or radiotherapy induced or after surgery for bilateral oophorectomy can be ruled out.

b) Discuss the additional investigations that you will undertake [5 marks].
I will carry out a pregnancy test as she has irregular menses based on her last menstrual period date. Chromosomal analysis for karyotyping is performed. Autoimmune disorder test for poly endocrinopathy, thyroid function test and fasting blood sugar are carried out. If there is suspicion of Addison’s adrenocortocotrophic hormone stimulation test is performed. Bone density scan to estimate bone mineral density

c) Discuss your subsequent management given that no underlying cause is found [10 marks]
She should be adequately and sensitively counselled about her condition. The diagnosis , nature of disease and support group like the Diasy Network should be informed from the very beginning of her care so that she can have adequate psychological support. She should be informed that although often infertile, there can still be spontaneous ovarian activity which can result in unscheduled bleeding, menstruation or even pregnancy. Her needs should be addressed which will include fertility and management of menopausal symptoms. She will need long term hormone replacement therapy (estrogen with cyclical progestogen) until the age of 50. The dose of estrogen increased depending on her vasomotor symptoms. Combined oral contraceptive pills are also an option instead of HRT as some prefer it because of their peers uses it. She should be reassured that there is no increase in risk of breast cancer in taking HRT until the average age of menopauseand that it is mainly to control her vasomotor symptoms and to protect against osteoporosis. If she has reduced libido with or without persistent tiredness, she mat benefit from testosterone implant or patch. For her fertility, donor oocyte IVF is the best option if she desires pregnancy. The success rate is equivalent to that of others who undergo conventional IVF. She should be informed that the success is determined by the age of the donated oocyte rather than her age.
Posted by Kiran  J.
A healthy 30 year old woman with a 2 year history of irregular periods has been referred to the fertility clinic because of primary infertility. Investigations show FSH= 54 iu/l, LH=35 iu/l. What will you tell her about the possible causes of her condition? [5 marks]. Discuss the additional investigations that you will undertake [5 marks]. Discuss your subsequent management given that no underlying cause is found [10 marks]

A:I will approach her in a sensitive manner and discuss that one of the possibilities is that due to the the pitutary hormones stimulating the ovaries in her body are high that could mean premature ovarian failure or resistant ovary syndrome.
In most of the cases no cause is found.In upto 40% of the cases it could be linked to a genetic underlying cause commonest bieng 45XO mosainc or 47XXY mosiac,fragile X syndrome.Autoimmune conditions can be associated although she is healthy but it can be an undiagnosed thyroid disease or pernicious aneamia.Other possible causes are ovarian injury inflicted by surgeries in the past,radiation/chemotherapy exposure or infections such as mumps or tuberclosis.


b|: Additional investigations include Pregnancy test as irregular periods,she may be pregnant with raised FSH,LH levels.If negative then for repeat FSH and LH 6 weeks after the first one in order to see presistantly raised FSH.Serum estradiol as low levels with raised Gonadotrophins point more towards ovarian failure.Serum prolactin,serum androgens,DHEA /DHEAS and 21 OH progesterone levels.Adrenal hormones can be checked as 2-5%patients have autoimmune adrenal insufficiency.Karyotype to assess for genetic /chromosomal abnormalities.Test for Fragile X syndrome.TSH and thyroid peroxidase antibodies.Imaging consists of TVS to see ovarian volume and size and also if any antral follicles present. A bone scan can be offered if there is confirmed premature menopause.Other investigations include Fasting lipid profile and OGTT to rule out hyperlipidimia and diabetes.Can also consider Anti mullarian hormone and Inhibin B to ovarian reserve.

C; Subsequent management consists of keeping in view the womans wishes.Involve the Endocrinologists,possible help from Psychologist as there could be element of distress and anxiety.GP at the primary level and inform of support groups available.Spontaneous ovulation and pregnancy can occur .If she wishes to get pregnant her options are discussed which consist of ovum donation After care ful councelling and referral to a fertility tertiary care centre.She may also opt for adoption.She should be informed that she is at risk of osteoprosis and cardiovascular disease due to premature onset of menopause .if she doesnt want to undertake the route of ovaum donation and pregnancy,she should be prescribed HRT.She can be given COCP along with HRT as she can get pregnant if spontaneuosly ovulates.HRT can be in the form of tablets,patches,vaginal gels or pessaries.General health advice like wight bearing excercises and healthy diet,cessation of smoking and alcohol should be imparted.
Follow up for Bone scans and auto immune disorders which can be done in primary care.There is a possibility of decreased androgen levels with premature ovarian failure and hence decreased libido which can be alleviated by androgen replacement.
Posted by Bgk H.
bgk

a. Autoimmune diseases possible cause of premature ovarian failure. This may be associated with thyroid disease or pernicious anaemia. Abnormal karyotyping is also a cause. This may be able to detect abnormal karyotyping such as Turner Syndrome (XO). And in some cases there is no identified cause. PCOS is a possible cause. This is most common endocrine disorder in reproductive age is . This is associated with irregular menses, oligo or anovulation, hyperandrogenisme and polycystic feature of ovary. Other rare cause is chemotherapy in the past, but unlikely as patient is healthy before.

b. Investigations are directed to her symptoms and family history. I will perform blood test to look for autoimmune disease. This includes anti thyroid antibodies and adrenal antibodies. I will perform a karyotyping testing to rule out any abnormal karyotyping such as turner syndrome. I will then perform a transvaginal ultrasonography to look for any polycystic appearance of the ovaries.

c. I will inform the patient the probable diagnosis of premature ovarian failure with no identified cause found. This associated with depletion of her follicles reserved. However spontaneous ovulation my still occur in 20% of patient. The consequences such as infertility are a recognised complication. Patient may experience a debilitating menopausal symptom that may require hormone replacement. HRT is also indicated for her bone protection as she is prone to have osteoporosis. Patient may also has the increase risk of cardiovascular complication such as myocardial infarction and hyper cholesterolaemia.

With regards of her fertility, other associated cause of infertility such as tubal patency test need to be done. Her husband semen analysis needs to be checked. This may then be able to proceed with the other management. She has the option of ovum donation. But she needs to have serial injection of hormonal support such as exogenous progesterone. She needs to be informed regarding the process and ethical issue. Surrogacy is another option. Both couple may need to be counselled and informed regarding the process and the ethical issue.
She can be treated conservatively as she may ovulate spontaneously however the chance is very small. She also can consider adoption. Patient info sheet and support group need to be given. Patient choice need to be respected. All options offered to her need to clearly documented inside her case notes.
Posted by A H.
AH
a) I will tell her that she has premature ovarian failure (POF) There are several causes but in the majority of cases (approximately 60% no cause is found.
Chromosomal abnormalities can cause POF, the most common being Turner\'s syndrome. It is also found in women with structural abnormalities, mosaicism, and in families with fragile X syndrome.
Autoimmune conditions can also cause POF, The most common association is hypothyroidism.The auto-immune disorder can be confined to the ovary.
Past infection with mumps or pelvic TB and metabolic conditions like galactosaemia can also be causative.
Iatrogenic causes include previous radiotherapy or chemotherapy, in particular alkylating agents.

b)Additional investigations include serum prolactin; hyperprolactinaemia can cause infertility, secondary amenorrhoea, or may be associated with hypothyroidism.
Serum androgens in particular DHEA and DHEA-S as well as 21-OH progesterone will be done to identify possible enzyme deficiency(for example 17 alpha hydroxylase deficiency) in the steroid biosynthesis pathway which may result in reduced estrogen synthesis.
TSH and anti thyroid anti bodies as well as antibodies to yhe ovary and adrenals will also be done.
Karyotyping for chromosomal abnormalities and to test for fragile X chromosomes will be relevant especially if there are features of Turners syndrome or a family history of mental retardation or POF.
Bone density measrements will be done to assess risk for osteoporosis and as a baseline to monitor treatment.
An ovarian biopsy will not be done as the dagnosis can be made from the history of amenorrhoea and persistently elevated FSH.

c) the patient will be counselled in in honest but sypathetic manner as it will be more difficult to accept the diagnosis given her history of infertility. Because she desires fertility it will be preferable to counsel her and her partner together.The nature of the disease will be explained to her. She will be advised of the differential diagnosis of resistant ovary syndome and that spontaneous ovulation and conception may occur. The long term risk of osteoporosis and abnormal lipid profile as well as cardiovascular disease due to POF will be explained to her.
Information leaflets and contact details for support groups will be given.
HRT will be offered after counselling about the different preparations, route of administration as well as risks and benefits. Combined estogen and progestogen will be needed for endometial protection. Intrauterine progestogen as the LNG-IUS which is also a contraceptive device may not be appropriate for her.
If she experiences decreased libido testosterone can be offered although its routine use is not recommended.
Dyspareunia due to vaginal dryness will be treated with vaginal estrogen.
She will be followed up to ensure compliance and monitor her cardiovascular and osteoporosis risks, and screen for autoimmune conditions.
Regading her infertility several options are available. These include expectant manaagement for an agreed time as spontaneous conception may occur.
Another option is oocyte donation with IVF and embryo transfer. Success rates are at least as for the general IVF programme.
Suurogacy, using the woman\'s own eggs can be done at a licensed centre She will be given contact details for COTS for necessary arrangements.
Other options are adoption or fostering.
Posted by R v P.
RVP

A healthy 30 year old woman with a 2 year history of irregular periods has been referred to the fertility clinic because of primary infertility. Investigations show FSH= 54 iu/l, LH=35 iu/l.
What will you tell her about the possible causes of her condition? [5 marks].


Considering her history and investigation results this is likely to be premature ovarian failure (POF). This should be explained to her in a sympathetic manner as the news is distressing to her and has long term implications both in terms of fertility and her own health.
Most cases of POF has no underlying cause found after investigations(idiopathic). Some may have a family history of POF, therefore, this should be explored.
Auto immune POF is also a recognised cause. Turner mosaics could be apparently healthy but may suffer POF.



Discuss the additional investigations that you will undertake [5 marks].


Her FSH/LH should be repeated after six weeks to check if the elevation of levels are sustained. Serum testosterone, SHBG and androstenidione should be measured and free androgen index calculated to check for hyperandrogenamia associated with poly cystic ovarian disease. Serum DHEAS should be checked to rule out adrenal tumors.
Thyroid profile and antibodies should be tested as auto immmune POF is associated with thyroid disease. Fasting glucose should be checked to rule out undiagnosed diabetes/carbohydrate intolarance secondory to auto immune disease.
Pelvic ultrasound should be offered to rule out PCO. Abdominal USS is indicated if adrenal tumors are suspected.
Karyotype is indicated if Turner mosaism is suspected.


Discuss your subsequent management given that no underlying cause is found [10 marks]

She should have MDT care including a gynaecologist, fertility expert, endocrinologist, GP and counsellors.
Findings should be explained to her in a sympathetic manner. Implications such as infertility, bone density loss and menapausal symptoms should be explained to her. Written information should be offered to her. She should be directed to support groups.

With regards to infertility the first option is do nothing. If she is keen to try assisted reproductive techniques, her partner should be offerd seminal fluid analysis. She should be referred to the regional fertility centre. IVF with egg donation is an option to her and this should be offered. She should be made aware that the resulting child has no genetic resemblence to her and this may have long term implications. Both the couple and the egg donor should be offered appropriate counselling.
Adoptation is also an option for her. This should be offered to her and if keen, referred to the relevent authorities.
POF increases her risk of osteophorosis if untreated. She could also be troubled with menapausal symptoms such as hot flushes night sweats and vaginal dryness. Therefore it is appropriate to offer her combined HRT. Preparations available to her include tablets, patches and vaginal rings. She should be offered the lowest effective dose and titrate against symptom relief. In the context of POF, she should be explained that HRT replaces hormones her ovaries would have naturally produced. Therefore her risks are thought to be minimal. HRT should be offered til the age of natural menopause(50). She should have at least yearly follow up.
It is appropriate to offer her bone protection with Vit D, Bisphosphonates and calcium to prevent osteophorosis. She should be managed by an endocrinologist in this regard. Annual DEXA scans to check bone density for follow up are appropriate.

She should be offerd general lifestyle advice such as healthy diet,regular exercise, stop smoking and alchohol.
Posted by millionaire2004 A.
Ag

A healthy 30 year old woman with a 2 year history of irregular periods has been referred to the fertility clinic because of primary infertility. Investigations show FSH= 54 iu/l, LH=35 iu/l. What will you tell her about the possible causes of her condition? [5 marks].

Explain to her about hypothalamic – pituitary – ovarian axis. Explain that FSH and LH are hormones produced from pituitary gland that needed to stimulate the ovary to produce sex steroids. Raised FSH/LH means that there is problem with ovarian function. It means that the ovaries are failing to develop follicles and produce sex steroids (premature ovarian failure). Tell her that it could be idiopathic . It could be due to pure gonadal dysgenesis (Swyer’s syndrome), where there is depletion of ovarian follicles to begin with. It is autosomal recessive genetic condition Genetic abnormalities such as 46X (turner’s syndrome) or 47XXY (Klinefelter syndrome) could cause accelerated ovarian follicle atresia. There could be problem with ovarian steroids production such as 17 alpha hydroxylase deficiency. There could be problem with FSH/LH receptors on the ovary. It is a genetic defect. It could be due to autoimmune conditions. It is usually associated with other autoimmune disease such as thyroid disease. It could also be due to previous infection such as mumps. Give her written information.

Discuss the additional investigations that you will undertake [5 marks].

Karyotyping to rule out genetic abnormalities (ie Turner’s syndrome, pure gonadal dysgenesis). Repeat FSH /LH level to confirm diagnosis of POF. Serum oestradiol level, which will be low in ovarian failure. Thyroid stimulating hormone (TSH) and anthyroid peroxidise antibody and antibody against adrenal gland because POF associated with other autoimmune disease. Transvaginal scan to look for presence of streak ovary. Husband seminal analysis for planning of future pregnancy. Bone scan to determine bone mineral density.

Discuss your subsequent management given that no underlying cause is found [10 marks]

Counsel the couple sensitively. Counsel the couple that spontaneous conception may still occur because there is still chance of spontaneous ovulation. However, the chances are very low. Her management is with multidisciplinary team consisting of reproductive medicine specialist,endocrinologist, gynaecologist with special interest in POF , councellor, specialist nurse.Assess their needs (ie fertility , menopausal symptoms). If the couple still wishes to get pregnant, her option is IVF with oocyte donation. Explain that the success rate is comparable to conventional IVF. Her other option is for adoption. Explain to her about the effect of POF to her own health. She has increased risk of osteoporosis, cardiovascular disease. Discuss about need for hormone replacement (oestrogen and progesterone). If the couple has no reproductive wishes, hormone replacement can be in the form of combined OCP. Arrange follow up with her GP to screen yearly for cardiovascular risks such as fasting lipid profile. If initial bone scan revealed osteopenia, she needs additional bone support such as bisphosphonate. Give her written information and contact of support group such as Daisy Network. Arrange follow up review.
Posted by Ida I.
I.

A) She has premature ovarian failure, and should be informed that the cause is unknown in most case. Genetic causes are associated with karyotype abnormalities such as 45XO or 47XXY. Abnormalities with the X chromosome such as Fragile X syndrome can also cause this condition. Autoimmune causes of premature ovarian failure would be associated with other underlying diseases such as thyroid disease or pernicious anaemia. Infection with mumps is also a cause, therefore a previous history of mumps is suggestive of an infective cause. Previous history of irradiation or chemotherapy can also predispose to this condition.

B) She would require serum estradiol to assess any circulating estrogen. Serum androgen levels, DHEA, DHEAS and 21- hydroxyprogesterone should be assessed to look for circulating androgens that could cause irregular menses. Serum prolactin levels to look for hyperprolactinemia that could cause irregular menses. Thyroid stimulating hormones and anti thyroid antibodies should be taken to screen for associated autoimmune thyroid disease. Karyotyping has to ascertain genetic abnormalities. Urine pregnancy test necessary to exclude pregnancy. Transvaginal scan done to look at the morphology of the ovaries and to exclude4 PCOS.

C) She should be informed regarding the diagnosis and the nature of the disease in a sensitive manner as the news may be distressing to her. She needs to know she is at higher risk of osteoporosis and cardiovascular disease. Menopausal symptoms, such as hot flushses, irritability and vaginal dryness needs to be discussed. HRT should be started for her in the lowest effective dose after thorough counselling regarding the benefits ( reduction of climecteric symptoms, osteoprotection) and its risks ( breast and endometrial cancer). Vaginal rings or pessaries can be used to treat vaginal dryness. Androgen replacement is not recommended, however is can be considered if she complains of reduced libido. Supplement calcium and Vitamin D tablets can be given to reduce the risk of osteoporosis
She can be informed that spontaneous ovulation can occur in rare cases, and there is also a remote chance of pregnancy. However if fertility is a concern, egg donation is recommended. Surrogacy and adoption are other alternatives that can be discussed.
Regular 6 monthly or yearly follow up has to be arranged to assess her physical and psychological status. She would need yearly bone density scans and mammograms, to assess osteoporosis and for the detection of breast pathology, respectively. She can be referred to the counselor or the psychiatrist if she has feelings of depression due to her condition. She should be referred to support groups, such as The Daisy Network. Written information should be provided for her.
Posted by NIRMALA M.
Nirmala
a. The diagnosis is most likely premature ovarian failure (POF). The most common cause of POF is idiopathic. Out of the recognized causes, immune mediated is the most common one. The other causes are resistant ovary syndrome, chromosomal abnormalities like Turners mosaic, fragile X syndrome, downs syndrome which is very unlikely, Infections like mumps oophoritis, chemotherapy and radiotherapy affecting ovarian function.

b. LH and FSH should be repeated to reconfirm the diagnosis. Other hormonal assays like oestradiol, free androgen assay, SHBG, DHEA, TSH and free T4, prolactin levels. Auto immune antibodies has to be checked to rule out autoimmune conitions affecting thyroid, adrenal, pancreas. Tests to identify pernicious anaemia, fasting blood sugar, anti insulin antibodies to rule out Diabetes. Chromosomal study to rule out turners, downs, Fragile x syndrome. USS to assess ovarian size and volume and to rule out PCOS and to know the endometrial thickness.

c. Once the diagnosis of premature ovarian failure is confirmed, the diagnosis should be broken down to her in a sensitive manner. It is a shocking news for her and time given for her to take the news. She should be explained that there is no cause for her condition. The issues related with her condition is management of fertility and treating her menopausal state. If she still wants to conceive, she should be referred to reproductive unit dealing with IVF pregnancy under Consultant care. She should be adequately counseled regarding further options and treatment. The options are ovum donation,IVF provided partners sperm count is normal, embryo transfer. If she is not willing for this, ovum donation, partners semen IVF and surrogacy could be offered. Adoption is another option. She should be counseled that sporadically she could ovulate. The next management point is to treat her menopausal state and to prevent osteoporosis and protect cardiovascular system. HRT should be started after appropriate counseling after assessing risks. Oral estrogen and progesterone or estrogen patches with oral progestrones could be tried depending upon patients wishes. If there is minimal vasomotor symptoms, tibolone could be started. Regular DEXA scans could be started to assess bone mineral density. Life style advise should be given to stop smoking, exercises, calcium rich diet. Leaflets and support group information given.
Posted by Dr Dyslexia V.
X
a) I will inform her that the most likely cause is premature ovarian failure. It occurs in about 0.1 to 1% woman before the age of 40. Most of the time the cause are idiopathic , while about 40% is due to genetic abnormality such as karyotype abnormality such as Turner’s syndrome XO and other disease such Fragile X syndrome. There is also association with autoimmune disease such autoimmune thyroid disease, adrenal disease (addison’s disease) and type1 diabetes mellitus. Other causes include infective in nature such as mumps. Other causes also include pelvic irradiation and chemotherapy.
b) Additional investigation include urine pregnancy test as it could have been a undetected pregnancy. Plasma estradiol level to assess if possibilities of spontaneous ovulation could occur. Serum thyroid stimulating hormone and antithyroid peroxidase antibodies taken assess presence of autoimmune thyroid disease. Renal profile to detect hyponatremia and hyperkalemia with serum adrenal antibody could be taken to detect autoimmune adrenal insufficiency. A glucose tolerance test done to detect type I Diabetes mellitus . Peripheral blood for karyotyping for detection of Turner’s syndrome and test for Fragile X syndrome. A bone density scan could be done as a baseline and for follow up as she is at risk of osteoporosis. Ovarian biopsy could be offered as well but it is of no clinical significance.
c) She should be informed of her diagnosis and its implication to her fertility in sympathetic manner. She should be informed in about 20% woman that there is spontenous ovulation do occur. Her option should include egg donation from donor with use of IVF and implantation the woman for pregnancy. Other options include surrogacy and adoption. She should be informed on her disease which could cause climacteric symptoms and early menopause. She could be treated with HRT for menstrual regulation and for osteoprotection. Decreased libido due to low androgen level also occurs and androgen replacement could be considered but not used routinely. Follow up should be done with bone density screening and to be vigilant on autoimmune disease if it occurs. Advice on healthy eating, exercise, weight reduction is also given as there is increased risk of cardiovascular disease. She could be reffered to support group like the daisy network.
Posted by Bobey B.
She should be informed sensitively of the diagnosis and that she is probably infertile.
She should be informed that the cause of POF is usually idiopathic .Some cases are attributed to autoimmune disorders such as autoimmune thyroiditis, or pernicious anaemia, polyglandular autoimmune syndrome , others to genetic disorders such as turner\'s syndrome and fragile X syndrome. Infections such as mumps oophoritis, herpes zoster and cytomegalovirus can cause POF. Galactosaemia, an autosomal recessive disorder is associated with premature depletion of ovarian follicles. Chemotherapy and irradiation can sometimes cause ovarian failure.
b) Serum oestradiol levels should be checked as spontaneous ovulation may occur. Serum prolactin, androgens, DHEA, DHEA-S 21 should be performed.
Thyroid stimulating hormone and free thyroxine is recommended, as thyroid dysfunction is more common in those with POF. It is useful to screen for thyroid auto antibodies to document of autoimmune thyroiditis ton aid further management. Adrenal antibodies should be checked, as it is associated with 2-5 % of cases. Karyotyping and chromosomal analysis is useful to identify X chromosome abnormality, Turner\'s syndrome and to test for X fragile chromosome. Anti-mullerian hormone (AMH) may be useful to detect the follicular reserve. Other tests include GTT, vitamin B12 as may be associated with pernicious anaemia .
TV/US to assess uterine size prior to considering fertility treatment and pregnancy, and it is useful to exclude polycystic ovary syndrome. It may reveal small ovaries without evidence of growing follicles.
Bone density scan should be performed to check for osteoporosis. C) Counselling should be given at diagnosis if appropriate. Patients with POF have infertility and hormone deficits. Early discussion and referral to dedicated fertility unit or centre is recommended. It is important for the woman to have a realistic understanding of fertility options. She should be informed that between 5 and 10 % of women with POF may spontaneously become pregnant .Currently no fertility treatment has been found to effectively increase fertility in women with POF. The option of ovum donation with in-Vitro Fertilization should offered after appropriate counselling . The couple may be offered the option of adoption, after they have been trying to conceive their own child.
It is important to initiate hormone replacement therapy, as untreated patients at greater risk of bone loss and osteoporosis. Furthermore, she may develop symptoms of oestrogen deficiency as vaginal dryness and hot flushes. Both of them will respond effectively to oestrogen therapy. The risk of cardiovascular or thromboembolic disease should be taken into account. HRT should then be continued until the natural age of menopause (50 – 52).
The combined oral contraceptive pill is a convenient and more socially acceptable if pregnancy is not desired for this young woman. However, it should be taken continuously to give bone protection. Annual monitoring of TSH, free thyroxine, Vitamin B12 levels should be initiated to screen for development of other associated conditions.
Bone densitometry should be considered at diagnosis . HRT is sufficient to improve bone densitometry . Vitamin D levels should be checked to determine whether supplementation is necessary. Repeating assessing bone densitometry should be considered . Verbal information should be supplemented with written information and support group addresses such as IPOFA.
what is best exercise to increase BMD? Posted by Dr.zartashia S.

walking

swimming

running