MRCOG PART II ESSAY 279 - Infertility

A healthy 30 year old woman and her healthy 37 year old partner are attending the fertility clinic because of a 3 year history of primary infertility. Following full investigations, no cause has been identified. (a) Critically evaluate the available treatment options [8 marks]. (b) Discuss the steps you would take to minimize the risk of major complications associated with the treatment of this couple [12 marks].

a.)The most probable diagnosis is unexplained infertility. The treatment options are expectant management ,IUI(intrauterine insemination), IVF( in vitro fertilisation) ICSI.

 As per NICE guidelines IUI can be offered upto six months with stimulated or unstimulated cycle.. Cumulative conception rates of 8-16% over 3-6 cycles  have been reported . It is simple easy to perform , does not need complex stimulation protocols .It is less expensive as compared to IVF and easily available. The risk of ovarian hyperstimulation syndrome is minimal. The disadvantage is that the  success rate is less than IVF /ICSI.

IVF is an effective treatment for unexplained infertility. It has a success rate of  >20-30% live birth rate per cycle.

It may not be available free of cost in NHS especially if couple has previous children.

It has some inherent complications like Ovarian hyperstimulation 5-30%.which can be life threatening in critical cases.  Risk of multiple pregnancy may be 10-15%. There is risk of ectopic pregnancy 2-20% , risk of visceral injury in case of embryo retrieval procedures. There can be intraperitoneal bleeding , infection due to egg  retrieval .

ICSI can be offered in IVF failure . It has advantage of micromanipulation of gametes and improved fertilisation rates as compared to IVF. The pregnancy rate is the same. The disadvantage is increased risk of y chromosome abnormalities in male fetus which needs more evidence.

b.) Complications of assisted reproduction are OHSS, multiple pregnancy, ectopic pregnancy, visceral injury.

OHSS (ovarian hyperstimulation syndrome ) can be prevented using the lowest dose of gonadotropin or shortest period o time. FSH dose should not exceed 450 units.

Use of gonadotropin antagonist is advocated. Use gonadotropin agonist by long down regulation protocol. Dose is individualised depending on age , bmi . Young women , BMI<30, with PCOS (polycystic ovaries) high risk of ohss should be given recombinant or urinary gonadotropins instead of HCG.

AMH (anti mullerian hormone )is being used as  marker to identify cases which may get ohss. Coasting is the process of stopping gonadotropin inj in case of excessive ovarian response in order to prevent ohss. If  response does not settle cycle cancellation and freezing embryos is an option to prevent life threatening ohss.

Cabgolin, quinqgolide are dopamine antagonist used to prevent ohss though strong evidence is lacking.

Avoid HCG in case estradiol >15000pg/ml, >20 follicles on usg.Units offering IVF should have protocols in place for early diagnosis and treatment ofOHSS

Multiple pregnancy prevented by single embryo transfer at blastocyst stage. Offer ultrasound monitoring for multiple follicles and explain risk of multiple pregnancy. For women less than 37 years offer single embryo transfer or first and second cycle as pregnancy rate same as double embryo.

Oocyte retrieval done by  trained operator or under supervision to avoid visceral injury. Conscious sedation can be used. Strict aseptic precautions and use o antibiotics can prevent infections. If difficulty anticipated procedure can be done under laparoscopy or after adhesiolysis.    Failure of IVF  can lead to distress and can be avoided by not doing embryo transfer if endometrial thickness is <5mm as chance of pregnancy is very less.

USG guided embryo transfer improves success rate. Avoid natural cycle IVF where there may not be ovarian stimulation.

 Ectopic pregnancy can be prevented by laparoscopic cliiping of fallopian tubes or salpingectomy of  hydrosalpinx.  

Early pregnancy failure may be avoided by use of progesterone for luteal phase support. Metformin has been used for cases of PCOS to prevent miscarriage but strong eveidence is lacking .

Psychological counselling is important to relieve stress ans anxiety. Adequate written information and support group like infertility.in details are provided.

A healthy 30 year old woman and her healthy 37 year old partner are attending the fertility clinic because of a 3 year history of primary infertility. Following full investigations, no cause has been identified. (a) Critically evaluate the available treatment options [8 marks]. (b) Discuss the steps you would take to minimize the risk of major complications associated with the treatment of this couple [12 marks].

expectant management is safe option , it doesnot carry risks like OHSS and multiple pregnancy. it has cumulative pregnancy rate of 80% and 90% after 12 months and 18months. it may increase stress , anxiety , unsatisfaction. it may not be acceptable to the couple. it include advice about avoiding smoking , NSAIDs , reducing alcohol. Advice about healthy diet and frequency of coitus also included.

empirical antiestrogens like clomiphene citrate can be an option for those couples who are not satisfied by expectant management and cant afford Assisted reproductive techniques.it carries risk of OHSS. 

6 cycles of unstimulated IUI is another option , not associated with risks like OHSS, it is costeffective package for younger women  but not more beneficial than expectant management over 6months.unstimulated fallopian sperm infusion may be more effective than uIUI. 

stimulated IUI has higher pregnancy rate , less cost effective . it is associated with higher risk pof multiple pregnancy.

IVF using single embryo transfer has lower multiple pregnancy rate , more effective in younger women.if IVF fails , ICSI ( intracytoplasmic sperm injection ) is another option .

b :    Risk of OHSS can be minimised by use of GnRH antagonists instead of agonists for ovarian stimulation. use of intravenous albumin around the time of oocyte retrieval also reduces its risk. coasting is a process of clinical and biochemical  judgement of ovarian hyperstimulation , followed by stopping gonadotrophins injections to reduce OHSS risk . it leads to atresia of small and intermediate size follicles hence risk of OHSS is reduced. use of progesterone for luteal phase support instead of HCG is another way of reducing the risk. use of lowest effective dose of HCG for ovarian stimulation can also reduce the risk of ovarian hyperstimulation. 

use of cabergoline from day of eggcollection has been proposed for reducing hyperstimulation of ovaries. cycle cancellation is another effective way but has psychological and financial implications.

risk of multiple pregnancy can be reduced by minimizing the number of embryoes transferred. RCOG recommends that no more than two embryo should be transferred in IVF cycles .selective single embryo transfer can reduce the risk of multiple pregnancy .

occyte retrieval has risks of intraperitoneal bleeding 0.2% and pelvic  infection 0.4% . it can cause injury to ovaries and other pelvic viscera. skilled , experienced operator , aseptic techniques and use of antibiotics can reduces these risks.

ovarian torsion can occur in early pregnancy after OHSS , early diagnosis and de torsion by laproscopy /laprotomy can preserve ovarian function.

ectopic pregnancy can occur in 2-11% of IVF  cycles . 1% risk of hetertrophic pregnancy . laproscopic clipping of hydrosalpinges/  salpingectomy reduce occurence of ectopic pregnancy in fallopian tubes.long term risks of ovarian cancer may be associated with gonadotrophin use and clomiphene use for more than 12months.

psychlogical morbidity , anxiety and stress can be reduced by psychological support , reassurance , partner support and wriiten information . 

this unexplained infertility, so the pregnancy can occur without treatment. i would give them advice on llife style reeduction alcohol, sexual intercourse at least every other day. but it carries anxiety to patients that no treatment.patient  can be given clomid tab 50mg twice 5 days for 6 cycle but there is a potential arisk of overian cancer. the cevical mucous can be be

this unexplained infertility, so the pregnancy can occur without treatment. can be given advice on llife style reduction alcohol, sexual intercourse at least every other day. but it carries anxiety to patients, that no treatment given.patient  can be given clomid tabs 50mg twice 5 days for 6 cycle but there is a potential arisk of overian cancer and it may decrease fertility by affecting cevical mucous. stimulated IUI can be given for 3 cycles with clomid or gonadotrophin injections. gonadotrophin inection can be given alone. IVF is an option but it is costly and carries risk overian hyper stimulation and multiple pregnancy. ICSI is an option but it carries risk of congenital malformation deletion of Y chromosome

b) psychological trauma can occurduring treatment, so support  is essential throughout . the major risk include overian hyperstimulation syndrome (OHSS) which can be decreased by identifying the risk factors like slim patient, previous OHSS, POCS, and avoid them. the step up regieme can be used.luteal  hcg injection not to be  given. GnRh antagonist can be used better than agonist . and even cancellation of the cycle can be done if severe. multiple pregnancy and it is complication like preterm delivery, preeclampsia, iugr,congenital malformation and feto fetal transfution. this can be reduced by follicular tracking,and transfer no more than two embryos, and if it occur fetal reduction can be done. during oocyte retrival infection and haemorrhage can occur which can be prevented by  expert person and antibiotic given. ectopic pregnancy can occur prevented proper transfer of embryos. congenital malformations can be prevented by preimlantations diagnosis and screening. also antenatal screening can be done

A healthy 30 year old woman and her healthy 37 year old partner are attending the fertility clinic because of a 3 year history of primary infertility. Following full investigations, no cause has been identified. (a) Critically evaluate the available treatment options [8 marks]. (b) Discuss the steps you would take to minimize the risk of major complications associated with the treatment of this couple [12 marks].

A)

this unexplained infertility, one option  the pregnancy can occur without treatment by expectent management, patients can be given advice on llife style reduction alcohol, sexual intercourse at least every other day. but it carries anxiety to patients because no treatment given them .patient  can be given clomid tablets 50mg twice 5 days for 6 cycle but there is a potential risk of overian cancer and it may decrease fertility by affecting cevical mucous. stimulated IUI can be given for 3 cycles with clomid or gonadotrophin injections. gonadotrophin inection can be given alone . IVF is an option but it is costly and carries risk of overian hyper stimulation and multiple pregnancy. ICSI is an option but it carries risk of congenital malformation deletion of Y chromosome

b) psychological trauma can occur during treatment, so support  is essential throughout . the major risk include overian hyperstimulation syndrome (OHSS) which can be decreased by identifying the risk factors before treatment  like slim patient, previous OHSS, POCS, and avoid them. the step up regieme can be used.luteal  hcg injection not to be  given. GnRh antagonist can be used better than agonist . and even cancellation of the cycle can be done if severe and freezing of embryos. multiple pregnancy and it is complication like preterm delivery, preeclampsia, IUGR, congenital malformation and feto fetal transfution. this can be reduced by follicular tracking,and transfer no more than two embryos, and if it occur fetal reduction can be done. during oocyte retrival infection and haemorrhage can occur which can be prevented by  expert person and antibiotic given. ectopic pregnancy can occur prevented proper transfer of embryos. congenital malformations can be prevented by preimlantations diagnosis and screening. also antenatal screening can be done

A) Offering ovulation induction with clomiphene citrate in one option. It increases the chance of pregnancy. It blocks estrogen receptors at hypothalamic pituitary axis which results in increased production of FSH and LH. Clomiphene induces ovulation in 70-85% of women with a 40-50% conception rate. It is recommended for a maximum of 12 cycles.  Treatment should be given only in circumstances which allow ultrasound monitoring of the ovary during at least the first cycle of treatment to ensure that they receive a dose that minimises the risk of  multiple pregnancy.

The other option is to offer  intra uterine insemination which increases the chance of pregnancy. Intra uterine insemination is more effective than no treatment.  During intra uterine insemination fallopian sperm perfustion should be offered using a large volume solution of about 4 ml which improves the pregnancy rates compared with standard insemination techniques. 

Another option is to offer three stimulated cycles of in vitro fertilisation. Ovulation induction is carried out by Human menopausal gonadotropin, urinary FSH and recombinanat follicle-stimulating hormone which are equally effective. The use of gonadotrophin therapy for ovulation induction is associated with risk of ovarian hyperstimulation and multiple pregnancy. 

Intracytoplasmic sperm injection should be considered if  a previous IVF cycle has resulted in failed or poor fertilization. This improves fertilsation rates compared to IVF but once ferltilisation is achieved the pregnancy rate is no better than with in vitro fertilisation.

(b) Discuss the steps you would take to minimize the risk of major complications associated with the treatment of this couple?

The major complications associated with ther treatment of this couple are multiple pregnancy with its associated complications. ovarian hyperstimulation and  risk of pelvic infection due to uterine instumentation.

Multiple pregnancy  is  associated with increased perinatal mortality  . Ultrasound monitoring of follicular activity and adjusting the dose of clomiphene can minimise the risk of multiple pregnancy.

The transfer of no more than three embryos according to HFEA guidelines minimises the risk of high order muliple births.

. Ovarian hyperstimulation syndrome Identification of Another major complication is ovarian hyperstimulation syndrome ( OHSS) . OHSS is characterised by ovarian enlargement, increased vascular permeability and fluid shifts. Mainly seen during ovulation induction by gonadotrophins.

Prediction of OHSS is important in preventing OHSS such as identifying some patient characteristics like young age , low body weight and previous OHSS which are associated with developing OHSS.  Cautious administration ovulation induction regimen such as  low doses of FSH  is appropriate for them. of Mon-follicular ovulation induction using gonadotrophin in a chronic low dose step-up regimen carries a lower risk of over- stimulation. 

For oocyte maturation, use of gonadotrophin antagonist rather than agonist is associated with reduced risk of OHSS.

In case of excessive ovarian response due to gonadotrophins, coasting is associated with reduced riks of OHSS. Coasting is stopping the gonadotrophin injection while continuing pituitary suppression. Lacks evidence from randomised studies. Coasting for more than 3 days is associated with reduced pregnancy rate. 

Single embryo transfer, blastocyst transfer and elective cryopreservation also reduce the risk of OHSS.

Providing luteal support with progesterone which is as effective as HCG also reduces the risk of OHSS.

In the presence of excessive ovarian response, cancellation of the cycle may be considered to avoid late OHSS but the risk of early OHSS is uneffected. Elective cryopreservation is an alternative to cancellation of the cycle.

For minimising the risk of pelvic infection at the time of egg collection no touch technique of the catheter tip should be used.  Before undergoing uterine instrumentation during IUI, egg collection or embryo transfer,she should be offered screening for chlamydia screening using NAAT testing of endocervical swabs or urethral samples to facilitate antibiotic prophylaxis. 

a)The lack of identifiable reason for unexplained infertility makes the treatment empirical.Conservative management, ovulation induction  with or without IUI, IVF-ET are the main approachesin the management of unexplained infertility. I will tell her that  approximately 60% of couples with unexplained infertility will conceive within 3 year . In this treatment there is no risks except waiting period , however results are less good with primary infertility.While considering this option woman’s age has to be considered , as in her case this can be a suitable one.Results of IUI are not better than conservative management . It is not expensive but need to collect and to insert timely.Ovulation induction with clomiphene citrate  with timed sexual intercourse can also be tried but results are not better than conservative managemaent, but instead carries the risks of multiple pregnancy.The cumulative pregnancy rate of COS with gonadotrophins and IUI is  around 40%but the benefit of IUI over timed sexual intercourse  is controversial and firm evidence is lacking. This option is less stressful, less physically demanding , less  expensive  and better pregnancy rate. IVF-Et is the last resort. It is  expensive. The cost of 3 COS –IUI  cycles is comparable to 1 IVF. It provides   detailed information of fertilized ovum and the embryo before implantation.

b) The Risks of OHSS can be prevented by identifying the high risk woman like young age, low BMI, Previous OHSS and history of PCOS and avoiding high doses  of Gonadotrophins and using    gonadotrophins  antagonist .Close follicular tracking to be done to monitor the growth  and to avoid HCG injection  if high estradiol level. To  abandone the  embryo transfer and cancel the ivf ycles ,or to freeze the embryo and later transfer when the estradiol levels are reduced to < 13000 pmole/l. This will reduce the severity of OHSS but not its incidence.  During oocyte retrieval  there is risks of visceral injuries , bleeding and infection and this can be minimized  if procedure is carried by experienced and  skilled person , approaching by transvaginal route under ultrasound guidance and antibiotic cover.Multiple pregnancies are associated with  serious maternal morbidity ,perinatal morbidity and mortality . To reduce the risks of multiple pregnancy  U.K. legislation and guidance has restricted  the number of embryo transfer to two except in woman > 40 years where maximum  3 can be transferred. Selective single embryo transfer  for selected good prognosis  patient is  recommended by the HEFA. If  high order multiple birth occurred ,every effort should be made to do selective reduction and minimizing multiple pregnancy  but this carries psychological and financial issuesRisks of ectopic  pregnancy can be reduced by  selective fallopian tube clipping and salpinghectomy and early scan and follow up .Risks of miscarriages can be reduced with progesterone  support in luteal phase due to suppressed  LH bydown regulation . Risks of anxiety and psychological  issues can be best minimized by good team   effort  , support groups and  providing   information leaflets.

a.        

a. Treatments include expectant management, which is associated with up to 92% live birth rate in women of this age, after 3 years of trying to conceive. This is unpredictable but is safe and cost effective, in the absence of pathology. It is however associated with continued anxiety for the couple.

Six cycles of Intrauterine insemination is a suitable alternative. This improves pregnancy rate in such couples and is recommended. It is cheaper than IVF, and carries minimal risks for the couple. Intrauterine deposition is preferred to intracervical deposition of semen. Pregnancy may be improved further by intrafallopian introduction of semen.  Couples should ideally be screened for STI eg Chlamydia, Hep B, HIV rubella immunity  prior to undergoing assisted reproduction, and vaccinated for rubella at least one month prior to attempting conception, and Hep B vaccination.

A further alternative is ovulation induction using antiestrogens clomiphene citrate or tamoxifen.  This carries the risk of OHSS and multiple pregnancy, and follicular tracking by ultrasound is recommended at least for the first cycle to gauge ovarian response. Serum estrogen is not recommended for follicular tracing as it is nonspecific and less accurate. In addition the lowest efficacious dose of clomifene/tamoxifen is recommended to reduce the risks of OHSS and multiple pregnancy.

IVF is an alternative for unexplained infertility. It is however expensive, has a high failure rate, carries a risk of OHSS, multiple pregnancy  and is stressful for the couple.  Three cycles of IVF is recommended for a given couple and a live birth rate of about 25-30% can be expected for this couple.  

An alternative such as adoption may be suitable for some couples. This can however be very stressful, and carries reduced satisfaction rates.

b.To minimise the risk of stress I will arrange for professional counselling for the couple prior to and during the period of treatment.

To reduce the risk of OHSS I will use unstimulated cycles for IUI. For ovulation induction with clomifene or tamoxifen I will use the lowest efficacious dose, accompanied by ultrasound follicular tracking for, at least, the first cycle, to reduce the risk of OHSS. I will gradually increase the dose in the absence of ovulation till an efficacious dose is reached. Similarly during IVF I will use the lowest efficacious dose of HMG, urinary-FSH or recombinant FSH starting from a low dose and gradually increasing it to achieve ovulation and minimise OHSS.

I will ensure egg collection is performed under ultrasound guidance to reduce the risk of vascular, bowel or other organ injury.

Where there is overwhelming ovarian response I will consider cycle cancellation, coasting, freezing the embryo for delayed transfer to minimise OHSS. I will use progestogen rather than HCG for luteal phase support, particularly where ovarian response has been excessive to reduce OHSS risk.

Multiple pregnancy is associated with increased risks of miscarriage, prematurity, growth restriction, perinatal mortality, and maternal complications eg anaemia, preeclampsia and caesarean delivery. I will consider single embryo transfer which reduces the risks associated with multiple pregnancy as well as OHSS. I will freeze any extra embryos for future needs, to reduce the need for repeated ovarian stimulation and associated risks of OHSS and multiple pregnancy.

I will ensure up to date cervical cytology to reduce the risk of delayed diagnosis of cervical precancer and /or cancer.

I will ensure testing of immune status for rubella, Hep B, and HIV screen to allow for vaccination and treatment, as appropriate. I will offer STI screening ,including Chlamydia , and treatment if positive, to reduce the risk of ascending infection during pelvic and uterine instrumentation.

I will ensure folic acid supplementation preconception and up to 12 weeks gestation to minimise the risk of NTDs.

A ] The treatment options are life style modification such as avoidance of smoking , alcohol intake and consumption of caffiene . the female should avoid Nsaid . this improves rate of fertility . if she is obese weight reduction will have good out come . The husbands occupation is also important, if he is working in place where there is increase in temperature this will effect his testes and decrease the sperm quality . tell the patient to take prepregnancy folic acid and check her rubella status and immunise if not immune . The success rate also depends on the age of the patient , it is better in patient between age group 23-35 yrs compared to a older patient . successful also if she has previous children . Take history about frequency of coitus , she should have regularl coitus  every 2-3 days . in case of unexplained infertility she can be  take clomifene citrate for stimulation of her ovaries up to 6 cycles .this helps ovulation and  results in pregnancy but risk of multiple pregnancy . she needs follicular  tracking atleast for the first cycle by USG . if this is not successful then stimulation of the ovaries with clomifene citrate and timed intercourse but this increases the patients anxiety. if she is resistant to clomifene citrate then she can have laproscopic ovarian drilling . this is helpful in female with PCOS , where her LH level  is decreased and results in pregnancy . the risk of multiple pregnancy and OHSS is not there and there is no need of follicular tracking  . patient has risk of exposure to anaesthetia and surgery . there is risk of damage to viscera and blood vessels . if the patient is ovulating she can have simple method of IUI or if she is not ovulatig she can have ovarian stimulation and IUI . success rate is about 20% per cycle but it causes patient anxiety .the other option is gonadotrophin stimulation of the ovaries and use of HMG or recombinant FSH or urinary FSH for luteal support but risk of ectopic pregnancy , multiple pregnancy and OHSS . she needs follicular tracking . other option is she can go for IVF where there is down regulation of the pitutary by gonadotrophins and give HMG or follicular/urinary FSH for luteal support but risk of multiple pregnancy , ectopic and OHSS . there is risk even at oocyte retrival by damage to viscera , bleeding and introduction of infection . this procedure is costly and not part of NHS especially if they have previous children . she can go for ICSI but risk of genetic abnormality and needs genetic councelling . other option is they can go for adoption but needs adequate councelling of the whole family including other children in the family . sometimes good emotional and psychological support is enough to achieve pregnancy . provide information leaflet and help from support group .

B] The steps taken to minimise the risk of IVF are as follows . minimal risk are avoided by , Adequate councelling  the couple  who  is going for IVF . discuss there benefits ,risk and  other available  options .provide information leaflet before hand . the couple needs to be seen in a dedicated fertility clinic where there is  protocol to avoid , diagnose and treat OHSS . the patient selection is atmost important   young patient ,who is not obese and who has modified her life style such as avoidance of alcohol, smoking improves the outcome .the couple is screened for HIV, HEPB ,if positive councel the couple about the implication of the infection  on the children . the major complications are minimised by.   if there is evidence of hydrosalphix laproscopic salphingectomy should be done . when there is evidence  of OHSS cancel the cycle  and freeze the embryos for the use in next cycle  . the purpose of this is to avoid ovulatory trigger by Hcg . by doing this  the risk of ovarian stimulation and oocyte retrival in the next cycle  is minimised . stimulation of the ovaries with antiestrogen clomifene citrate but may be ineffective . down regulation  of pitutary is done by low dose gonadotropin agonist  and HMG , giving in pulsatile fashion decreases the rate of OHSS   .  follicular tracking is done by USG for early identification of OHSS and early intervaention  . coasting is done if there are more number of follicles seen  discontinue gonadotropin and delaying luteal support with HCG or urinary/follicular FSH .reducing the number of oocytes recovery may compromise the pregnancy . instead of using HMG or urinary/recombinant FSH  for luteal support  , luteal support can be provided with progesterone . routiene use of HMG for luteal support is not indicated . prophylactic use of albumin or HES at the time of oocyte retrival . follicular aspiration can be done but risk of damage to surrounding viscera and introducing infection .follicular flushing is not needed if about 3 follicles are there . trained ,experience person should do oocyte retrival as risk of haemorrhage, trauma and introducing infection in the pelvis . consious sedation analgesia must be used at the time of oocyte retrival . not more than two embroys must be implanted according to rcog  guidelines  and usg guided implantaion with the endometrial thickness more than 5mm is needed for improved success rate . rest of not more than 20 mins is needed after embroy implantation . the patient must be councelled if she has any abdominal pain or distention she should report to the hospital . provide her 24 hr hospital contact number.  early identification and prompt treatment of OHSS improves the outcome .  

A healthy 30 year old woman and her healthy 37 year old partner are attending the fertility clinic because of a 3 year history of primary infertility. Following full investigations, no cause has been identified. (a) Critically evaluate the available treatment options [8 marks]. (b) Discuss the steps you would take to minimize the risk of major complications associated with the treatment of this couple [12 marks]. A) Treatment options of unexplained infertility are expectant management.ovulation induction by antiestrogen like clomiphen citrate or Tamoxiphen.and assissted reproductive techniques (ART). expectant management trough councelling the couple about increment of cumulative pregnancy rate with it.advice about decrease weight if BMI >30 to gain weight if BMI <18 and stop smoking increase spontenous pregnancy rate.Timed intercourse is not recommended as it is associated with increase anxiety.however.expectant management associated with decrease satisifaction and increase anxiety of the couple . Ovulation induction with antiestrogen such as clomiphen citrate or Tamoxiphen can be tried but it is associated with side effects of the drugs such as headach ,visual disturbances,abdominal pain and hot flush.moreover it is associated with risk of ovarian hyperstimulation syndrome and multiple pregnancy. IUI is more effective than no treatmet and it can be used with stimulated or unstimulated cycle.But for these couple unstimulated cycle is recommended as it is associated with decrease risk of multiple pregnancy or hypestimulation syndrome.also it is more cost effective.IIUI can be used for 6 cycles. IVF is another option and can be tried for up to 3 cycles. IVF associated with risk of ovarian hyperstimulation syndrome and multiple pregnancy and it is expensive. lastly adoption may be telast resort but it carries more anxiety and low satisfication. B)one of theMajor complictions of treatment option is Ovarian hyperstimulation syndrome (OHS).this can occured with ovarian stimulation by gonadotrphin agonist in IVF cycle and to lesser extent with clomiphen citrate.Coasting through holding of gonadotrophin injection leads to atrophy of small and intermediate follicle while.large follicle contine to grow. usage of gonadotrophin antagonist provide suppression of endogenous gonadotrophin release without impairing pitutary senstivity to GnRH.luteal phase support with progeterone instead of HCG decrease risk of OHS. Canellation of the cycle and freezing of the embryo is another option. multiple pregnancy caries high risk of perinatal morbidity and mortality ad can be decreased through usage of unstimulated IUI.In IVF HFEA recommendes no more than 3 embryoes transfere and RCOG recommendes no more than 2 embruo transfre. In OOcyte retrieval there is isk of intraabdominal haemorrage 0.4% infection 0.2% and injury of ovarian tissue.expirenced obstetrician and antibitics can reduce it. Ovarian Torsion can happened with hyperstimulatied ovaries manifested by sudden sever abdominal pain with nausea and vomiting.early diagnosis of it and untwisting through laparoscopy or laparotomy can perserve the ovaries. there is increase risk of Ectopic pregnancy with ART and needs early dignoses and treatment . there ar long term risk of ovarian cancer .Rcog recommendes 12 months of clomiphen citrate to decrease this risk. the couple need psychological support to minimize risk of psycological morbidity.

The couple seem to have Unexplained Infertility and they should be dealt with in a sensitive manner.No treatment and offering expectant management would not relieve their anxiety.Lifestyle modifications like weight reduction,avoid smoking,alcohol ,recreational drugs can be suggested as an adjunct to improve treatment success rates.Available options are ovulation induction using Clomiphene citrate, Intrauterine insemination(IUI) , Invitro fertilisation(IVF)    and Intracytoplasmic sperm injection(ICSI) the last two being ART(ASSISTED REPRODUCTIVE TECHNIQUES). Folic acid prophylaxis 0.4mg,screen for HIV,Hbsag,rubella immunity before treatment.

    OI with clomiphene can be tried for 6 cycles with ultrasound monitoring for follicular maturity,success rates upto 40%.But risk of multiple pregnancy 6 to 12% and endometrial thinning.Use beyond 12 cycles increases risk of ovarian cancer. IUI is another option can be tried for 6 cycles.Avoiding clomiphene  before IUI minimises chances of multiple pregnancy  called “Unstimulated cycle” .FALLOPIAN SPERM PERFUSION is a technique in IUI using lot of perfusion fluid with the sperms,giving better success rates. IVF is a costlier alternative,not funded by the NHS if the couple have children previously.Can be offered for 3 cycles with success rates of 20% for this couple.It involves downregulation of the womans ovaries using GnRH agonists,ovulation induction with gonadotrophins,oocyte  retrieval,sperm collection, IVF and embryo transfer(not more than 3 as per HFEA Guidelines). If there is a problem in fertilisation ICSI can be offered but if male partner has y chromosome abnormalities,genetic counselling is required.If risks of genetic problems Donor sperms an option as per British Andrology Society  Guidelines.     

           Problems associated with treatment  are Ovarian hyperstimulation syndrome OHSS mild in 33% moderate to severe in 6 to 8%.increased risk if polycystic ovaries,formation of >20 follicles ,multiple pregnancy.Enlarged ovaries prone for torsion,may need emergency surgery for undoing torsion .OHSS can be prevented by identifying risk factors,using minimum doses of gonadotrophins required for successful ovulation,avoiding HCG injection and avoiding further gonadotrophins if >20 follicles on scan or serum estradiol >12000 pg/mlcalled COASTING.Risk of multiple pregnancy in IVF can be minimised by following HFEA Guidelines of not >3 embryos transfer or not >2 as per the RCOG.IUI with unstimulated cycle also minimises multiple pregnancy risks.Problems with oocyte retrieval are pain,can be done under sedation as per RCOG guidelines,infection0.2%,intraperitoneal bleed0.4%,injury to viscera minimised if done by skilled personnel.Risk of ectopic pregnancy 6% can be minimised by surgical removal of hydrosalpinx if present ,also improves success rates in IVF.Miscarriage rates can be minimised by avoiding embryo transfer if endometrium is thin and supporting pregnancy with progesterone ,HCG if gonadotrophins were used in induction .Psychological morbidity to couple in case if treatment fails,or complicatons occur has to be dealt with by trained counsellors.Most important would be to offer information leaflets to couple and website details like www.nhsdirect.nhs.uk as ,involving them in decision making contributes to treatment success.                                                                               

a) this is unexplained infertilty.I'd be sensitive and empathetic as unexplained cause gives more pshycological stress to the couple. I'll explain to them that they have a good chance(90%) of spontaneous conception with conservative/expectant management like regular(every alternate day) intercourse,healthy lifestyle(reduce achohol,avoid smoking, exercise),avoid NSAIDS particularly around ovulation(midcycle).But this maynot be acceptable to them as they have been trying for 3 years.

the other option would be to offer medical management by offering ovulation induction. it has been shown that pregnancy rate may improve with ovulation induction in unexplained infertility by increasing the chance of fertilisation. this can be combined with timed intercourse or intra-uterine insemination. this means more medicalisation , increases anxiety , and needs more monitoring(regular ultrasounds for follicular development ),increases risk of ovarian hyperstimulation,multiple pregnancy, hospitalisation.

if that fails, there is the option of IVF. The low implantation rate of 25% -30% should be explained. the risk of multiple pregnancy, heterotopic pregnancy(uterine and ectopic pregnancy),ovarian hyperstimulation should be discussed in detail. the option of adoption would also be discussed sensitively.

b)-the major complications of treatment in this couple are ovarian hyperstimulation(OHSS), multiple pregnancy, ectopic pregnancy, miscarriage,increased morbidity, hopsitalisation, psychological stress for both partners.I'd offer detailed discussion regarding the benefits and risks associated with the options of treatment available to them. help them with written information, provide contact numbers of counsellors, and advice about support groups.

if using ovulation induction, try with clomiphene citrate first before going on to GnRH analougues as less risk of OHSS, multiple pregnancy with clomiphene. if using GnRh analougues, would offer long antagonist cycle(less flare symptoms).Inform,provide written information about signs and symptoms of OHSS, Ectopic pregnancy, for early diagnosis and management. Offer early ultrasound for fetal viability, location. Offer progesterone support in early pregnancy to reduce risk of miscarriage(not evidence based).

A healthy 30 year old woman and her healthy 37 year old partner are attending the fertility clinic because of a 3 year history of primary infertility. Following full investigations, no cause has been identified. (a) Critically evaluate the available treatment options [8 marks].

These couples have unexplained infertility. The available treatment options include ovulation induction using clomifene citrate as this has shown that it is better than expectant management in females with unexplained infertility as they increase the chances of pregnancy. this should be balanced against increased risk of multiple gestation. ultrasound monitoring of follicles should be offered in the first cycle of ovulation induction using Clomifene citrate to ensure that they receive a dose that minimises the occurence of multiple gestation. this may be used up to 12 months, as longer duration of use may be associated with theoretical risk of ovarian cancer. The couple should be informed that clomifene citrate has side effects of visual disturbance, flushing, headache.

If this was unsuccessful, patient can be offered intrauterine insemination IUI up to 6 times becauses this increases the chances of pregnancy. It is better than expectant management. stimulated IUI ie use of IUI with  ovulation induction is not recommended in ovulatory women as such in this lady even though it is associated with higher chances of pregnancy than in unstimulated IUI, because it increases the risk of multiple gestation. Fallopian tube perfusion for insemination using large volume solution of 4ml should be offered as it has been showed to improve pregnancy rates as compared to standard insemination.

This couple may be offered up to three stimulated cycles of in vitro fertilisation IVF, which entails stimulation of ovaries using gonadotrophins, collection of eggs, and fertilisation outside the body using mom's eggs and father's sperms and trasfering back the embryo into the womb.

ICSI which is intracytoplasmic sperm injection may be offered in case of IVF failed fertilisation. It envolves injection the sperm directly into the egg thus bypassing the natural barriers of selection. This may be associated with chromosome y microdeletions and counselling about this occurrence should be discussed wtih the couple. 

 (b) Discuss the steps you would take to minimize the risk of major complications associated with the treatment of this couple [12 marks].

Major complications associated with this couple's treatment include occurence of ovarian hyperstimulation synrome OHSS and multiple pregnancies. OHSS can be reduced by using step up regimen in controlled ovarian hyperstimulation using gonadotrophins which consists of starting with low dose of FSH ie 75 iu daily until acheivement of follicular development and criteria of HCG. this carries less risk of OHSS than step down regimen. Another option is use of GnRH antagonist during IVF regimen, as it results in fewer oocytes, lower estradiol level and less OHSS as compared to GnRH agonist regimen.

In the event of excessive ovarian response, stoppage of ovarian stimulation by gonadotrophins while continuing pituitary suppression, a process called Coasting will lead to atresia of small and medium sized follicles, while dominant folllicle withdegree of FSH independence will continue to grow. This way will lead to less OHSS. Studies suggest that if coasting is continued >4 days the cycle should be abandoned as there detrimental effects on pregnancy rates. Cancellation of cycle is the most effective way of preventing OHSS, bu carries an emotional and finacial cost.

Another way of reducing OHSS is ovarian maturation using recombinent LH which leads to similar effects and pregnancy rates as HCG but has lower half life. Alternatively GnRHagonist can be used to trigger ovarian maturation in GnRH antagonist cycles as it has lower half life than HCG, but this is associated with deficiency in luteal phase thus requiring modified luteal support. Cryopreservation of all embryos avoids exposure to endogenous HCG of pregnancy thereby avoiding the possibility of late OHSS, but early OHSS can still occur. Transferring a single embryo is helful in both decreasing risk of OHSS and reducing risks of multiple gestation. Also use of progesterone instead of HCG for luteal phase support in cycles where pituitary gonadotrophin were suppressed is equally effective with lower risk of OHSS. Use of low dose cabergoline 0.5 mg /day startind day of egg collection, has been advocated in high risk patient  to decrease incidence and severity of OHSS, however late OHSS occuring due to endogenous HCG of an early pregnancy  would still occur.

Other potential risks including ectopic pregnancy, intraabdominal bleeding, infection can be managed and their morbidity minimised by increased vigilance and proper investigation of abdominal pain in women that have undergone controlled ovarian stimulation.

The psycological stress associated with fertility treatments should be addressed by proper counselling by a specialist. Written info should also be provided as well as contact numbers of support groups.

Ans: This is most probably a  case of unexplained infertility. Couple can be given the option of expectant management, for up to a year after investigations. Though 60 % conceive within 3 years, pregnancy rate after infertility of 3 years is about 15%, and after 4 years  it is 14 %. It has advantage of avoiding  artificial ovarian stimulation and its associated risks and costs. However as chances of conception decrease  with increasing duration of pregnancy, this may not be an acceptable offer for them.  It may result in further psychological stress in couple. 

She can be informed about ovulation induction with clomiphene citrate alone. It has risks of  ovarian hyperstimulation syndrome(OHSS)  and multiple pregnancy(MP), though risks are lower than gonadotrophins or In Vitro fertilization(IVF).However it does not increase pregnancy rate, or live birth rate .They can be given trial artificial insemination , with 6 or more intra uterine insemination( IUI )cycles . She can have controlled ovarian stmulation(COS)in up to 3 cycles. It has a of pregnancy  rate of 10 to 15%. It is less demanding emotionally and physically than IVF. It involves lower cost as compare to IVF. Cumulative pregnancy rate is upto 40 %.It is associated with the risks of OHSS and MP.

They can be given the option of Up to 3 complete treatment cycles of IVF and embryo transfer(ET)  with or without Intracytoplasmic  sperm injection (ICSI). IVF has higher risk of  OHSS(mild  33% ,moderate to severe 3-8%), and MP.  It involves invasive procedure, like oocyte retrieval and associated risks, like infection, bleeding and organ damage. I will tell them that live birth rate in her age group is more than 20%.  Success rate is higher in nonsmokers, and those avoiding caffein and alcohol.  Intracytoplasmic  sperm injection (ICSI) if IVF cycle fails.

 I will tell her Gamete intra fallopian transfer( GIFT) is an option, but that there is insufficient evidence to recommend it  in preference to IVF. It is associated with increased pregnancy rate. However it is invasive, performed under GA/laparascopy and  carries their associated risks.It also increases the risk of ectopic pregnany.

Adoption, remains options if despite all treatments there is failure to conceive. May be associated with psychological stress and post adoption depression.

b) IVF is associated with risks of OHSS and MP. OHSS is is associated with serious maternal morbidity  and can be life threatening. MP is associated with higher perinatal morbidity and mortality and maternal morbidity. Awareness and early recognition of OHSS is important.  She should be given adequate verbal and written information regarding this condition, its symptoms, risk factors and treatment. She will be advised to keep it with her at all times, and report in case of symptoms like abdominal pain and bloating, nausea and vomiting.  In the department, there should be protocol in place for prevention, diagnosis and management of OHSS .Controlled ovarian stimulation reduces the risk of OHSS and MP. Downregulation with Gonadotrophin releasing hormone GnRH  agonist done (long protocol). If she has higher risk of OHSS( low body weight, previous OHSS), GnRH antagonist can be considered. Ultrasound monitoring of ovarian response  helps in early recognition and management of complications. To trigger ovulation  recombinant Luteinizing hormone instead of HCG  also decreases  risk . Ovulation will not be triggered if estradiol levels are more than 15,000 pm/l, or there are more than 20 follclies on ultrasound . Coasting   can considered if esradiol levels are rising , as it decreases risk of OHSS and cycle cancellation. In this process administration of hCG is  withheld until serum E2 have decreased . With oocyte retrieval, there is 0.2 % risk of hemorrhage ,0.4 % risk of pelvic infection , and risk of injury to ovary/ pelvic viscera. If done under GA/ Laparoscopy, carries risks associated with procedure, eg organ, vascular injury, and risks of anaesthesia. Risks are lower if procedures are carried out by experienced operator . Anaesthesia can be avoided by use of conscious sedation.  Single embryo transfer decreases risk of multiple pregnancy. No more than 2 embryos will be transferred even during any IVF cycle. Supernumery embryos can be cryopreserved and used in next cycle. This avoids the risk of stimulation next cycle.  ET will not be done if endometrial thickness less than5 mm to avoid risk of failure.

Luteal support with progesterone( instead of HCG) is associated with lower risk of OHSS. If mild OHSS , couple  is advised to avoid intercourse and strenuous exercise, as  there is  increased risk  ovarian torsion/ trauma . If moderate to severe OHSS, admission and multidisciplinary management will be ensured. Rarely termination of pregnancy may be needed.  Infertility is associated with psychological morbidity. I will arrange counselling by health care personnel  not directly involved with the treatment before, during and after treatment.

Ovarian  cancer ,risk controversial.  Clomephene will not be used for more than 6 months. Use of  ovulation induction or ovulation stimulation agents will be  limited to lowest effective  doses and duration.

a.)The most probable diagnosis is unexplained infertility. What else could it be? You need to give the examiner confidence at the begining of your answer  The treatment options are expectant management ,IUI(intrauterine insemination), IVF( in vitro fertilisation) ICSI.

 As per NICE guidelines IUI can be offered (1)  upto six months with stimulated or unstimulated cycle.. Cumulative conception rates of 8-16% over 3-6 cycles  have been reported . It is simple easy to perform , does not need complex stimulation protocols .It is less expensive as compared to IVF and easily available. The risk of ovarian hyperstimulation syndrome is minimal. The disadvantage is that the  success rate is less than IVF /ICSI is success rate higher than with expectant management?.

IVF is an effective treatment for unexplained infertility. It has a success rate of  >20-30% live birth rate per cycle .

It may not be available free of cost in NHS why not??? especially if couple has previous children read the question – primary infertility.

It has some inherent complications like Ovarian hyperstimulation 5-30%.which can be life threatening in critical cases.  Risk of multiple pregnancy may be 10-15%. There is risk of ectopic pregnancy 2-20% , risk of visceral injury in case of embryo retrieval procedures. There can be intraperitoneal bleeding , infection due to egg  retrieval (1).

ICSI can be offered in IVF failure . It has advantage of micromanipulation of gametes and improved fertilisation rates as compared to IVF. The pregnancy rate is the same. The disadvantage is increased risk of y chromosome abnormalities in male fetus which needs more evidence. What is the evidence for this?

b.) Complications of assisted reproduction are OHSS, multiple pregnancy, ectopic pregnancy, visceral injury.

OHSS (ovarian hyperstimulation syndrome ) can be prevented using the lowest dose of gonadotropin (1) or shortest period o time. FSH dose should not exceed 450 units.

Use of gonadotropin antagonist is advocated. Use gonadotropin agonist by long down regulation protocol. Dose is individualised depending on age , bmi (1). Young women , BMI<30, with PCOS (polycystic ovaries) ARE THESE THE SAME??? high risk of ohss should be given recombinant or urinary gonadotropins instead of HCG.

AMH (anti mullerian hormone )is being used as  marker to identify cases which may get ohss. Coasting (1) is the process of stopping gonadotropin inj in case of excessive ovarian response in order to prevent ohss. If  response does not settle cycle cancellation and freezing embryos is an option to prevent life threatening ohss (1).

Cabgolin, quinqgolide are dopamine antagonist used to prevent ohss though strong evidence is lacking.

Avoid HCG in case estradiol >15000pg/ml, >20 follicles on usg (1).Units offering IVF should have protocols in place for early diagnosis and treatment ofOHSS

Multiple pregnancy prevented by single embryo transfer (1) at blastocyst stage. Offer ultrasound monitoring for multiple follicles and explain risk of multiple pregnancy ? in IVF??. For women less than 37 years offer single embryo transfer or first and second cycle as pregnancy rate same as double embryo. Written already

Oocyte retrieval done by  trained operator or under supervision to avoid visceral injury. Conscious sedation can be used. Strict aseptic precautions and use o antibiotics can prevent infections. If difficulty anticipated procedure can be done under laparoscopy or after adhesiolysis.    Failure of IVF  can lead to distress and can be avoided by not doing embryo transfer if endometrial thickness is <5mm as chance of pregnancy is very less.

USG guided embryo transfer improves success rate. Avoid natural cycle IVF where there may not be ovarian stimulation.

 Ectopic pregnancy can be prevented by laparoscopic cliiping of fallopian tubes or salpingectomy of  hydrosalpinx in a woman with unexplained infertility? Read the question.  

Early pregnancy failure may be avoided by use of progesterone for luteal phase support. Metformin has been used for cases of PCOS to prevent miscarriage but strong eveidence is lacking does this woman have POCS?.

Psychological counselling is important to relieve stress ans anxiety. Adequate written information and support group like infertility.in details are provided.

A healthy 30 year old woman and her healthy 37 year old partner are attending the fertility clinic because of a 3 year history of primary infertility. Following full investigations, no cause has been identified. (a) Critically evaluate the available treatment options [8 marks]. (b) Discuss the steps you would take to minimize the risk of major complications associated with the treatment of this couple [12 marks].

expectant management is safe option , it doesnot carry risks like OHSS and multiple pregnancy. it has cumulative pregnancy rate of 80% and 90% after 12 months and 18months will a couple like this have an 80% chance of a pregnancy over the next 12 months???. it may increase stress , anxiety , unsatisfaction. it may not be acceptable to the couple (1) why do you think this will not be acceptable?. it include advice about avoiding smoking , NSAIDs , reducing alcohol. Advice about healthy diet and frequency of coitus also included.

empirical antiestrogens like clomiphene citrate can be an option for those couples who are not satisfied by expectant management and cant afford Assisted reproductive techniques.it carries risk of OHSS (1) what is the success rate? Critically EVALUATE. 

6 cycles of unstimulated IUI (1) is another option , not associated with risks like OHSS, it is costeffective package for younger women  but not more beneficial than expectant management over 6months so how can this be cost-effective? It is ineffective (no better than no treatment) and costs money – can that be a good use of money (cost-effective)??? .unstimulated fallopian sperm infusion may be more effective than uIUI ? evidence. 

stimulated IUI has higher pregnancy rate , less cost effective??? compared to what??. it is associated with higher risk pof multiple pregnancy.

IVF using single embryo transfer has lower multiple pregnancy rate lower compared to what?, more effective in younger women younger than what?? You are given her age in the question.if IVF fails , ICSI ( intracytoplasmic sperm injection ) is another option .

b :    Risk of OHSS can be minimised by use of GnRH antagonists instead of agonists for ovarian stimulation. use of intravenous albumin around the time of oocyte retrieval also reduces its risk ? evidence. coasting is a process of clinical and biochemical  judgement of ovarian hyperstimulation , followed by stopping gonadotrophins injections to reduce OHSS risk (1). it leads to atresia of small and intermediate size follicles hence risk of OHSS is reduced. use of progesterone for luteal phase support instead of HCG is another way of reducing the risk. use of lowest effective dose (1) of HCG for ovarian stimulation can also reduce the risk of ovarian hyperstimulation. 

use of cabergoline from day of eggcollection has been proposed for reducing hyperstimulation of ovaries. cycle cancellation is another effective way (1) but has psychological and financial implications.

risk of multiple pregnancy can be reduced by minimizing the number of embryoes transferred. RCOG recommends that no more than two embryo should be transferred in IVF cycles .selective single embryo transfer can reduce the risk of multiple pregnancy (1).

occyte retrieval has risks of intraperitoneal bleeding 0.2% and pelvic  infection 0.4% . it can cause injury to ovaries and other pelvic viscera. skilled , experienced operator , aseptic techniques and use of antibiotics can reduces these risks (1).

ovarian torsion can occur in early pregnancy after OHSS , early diagnosis and de torsion by laproscopy /laprotomy can preserve ovarian function.

ectopic pregnancy can occur in 2-11% of IVF  cycles . 1% risk of hetertrophic pregnancy . laproscopic clipping of hydrosalpinges/  salpingectomy reduce occurence of ectopic pregnancy in fallopian tubes in a woman with unexplained infertility?.long term risks of ovarian cancer may be associated with gonadotrophin use and clomiphene use for more than 12months.

psychlogical morbidity , anxiety and stress can be reduced by psychological support , reassurance , partner support and wriiten information . 

this unexplained infertility, so the pregnancy can occur without treatment how likely? . can be given advice on llife style reduction alcohol, sexual intercourse at least every other day. but it carries anxiety to patients, that no treatment given (1).patient  can be given clomid tabs 50mg twice 5 days any 5 days???  for 6 cycle but there is a potential arisk of overian cancer is there?? How high is the risk and where is the evidence?? and it may decrease fertility by affecting cevical mucous so does clomid increase or decrease fertility? It cannot do both. stimulated IUI can be given for 3 cycles with clomid or gonadotrophin injections. gonadotrophin inection can be given alone how likely is this to succeed? Critically EVALUATE. IVF is an option but it is costly This couple will not need to pay for their treatment and carries risk overian hyper stimulation and multiple pregnancy (1). ICSI is an option but it carries risk of congenital malformation deletion of Y chromosome

b) psychological trauma can occurduring treatment, so support  is essential throughout . the major risk include overian hyperstimulation syndrome (OHSS) which can be decreased by identifying the risk factors like slim patient, previous OHSS, POCS, and avoid them. So you will not offer IVF to a slim woman? the step up regieme can be used.luteal  hcg injection not to be  given. GnRh antagonist can be used better than agonist . and even cancellation of the cycle (1) can be done if severe. multiple pregnancy and it is complication like preterm delivery, preeclampsia, iugr,congenital malformation and feto fetal transfution. This is a complication of monozygotic twins and cannot be reduced by single embryo transfer or follicular tracking this can be reduced by follicular tracking,and transfer no more than two embryos (1), and if it occur fetal reduction can be done will you reduce a twin pregnancy?. during oocyte retrival infection and haemorrhage can occur which can be prevented by  expert person and antibiotic given (1). ectopic pregnancy can occur prevented proper transfer of embryos meaning. congenital malformations can be prevented by preimlantations diagnosis and screening how does this prevent congenital malformations???? . also antenatal screening can be done

You have only used a fraction of the space / time provided. This should prompt you to do more reading and then re-attempt the question

A) Offering ovulation induction with clomiphene citrate in one option. It increases the chance of pregnancy. It blocks estrogen receptors at hypothalamic pituitary axis which results in increased production of FSH and LH. Clomiphene induces ovulation in 70-85% of women with a 40-50% conception rate not true for women with unexplained infertility and the available evidence suggests pregnancy rates not increased. It is recommended for a maximum of 12 cycles.  Treatment should be given only in circumstances which allow ultrasound monitoring of the ovary during at least the first cycle of treatment to ensure that they receive a dose that minimises the risk of  multiple pregnancy. Are there other risks?

The other option is to offer  intra uterine insemination which increases the chance of pregnancy available evidence is that it does not. Intra uterine insemination is more effective than no treatment no it is not.  During intra uterine insemination fallopian sperm perfustion should be offered using a large volume solution of about 4 ml which improves the pregnancy rates compared with standard insemination techniques. Are there any disadvantages? CRITICALLY evaluate

Another option is to offer three stimulated why only 3? cycles of in vitro fertilization what is the success rate? EVALUATE. Ovulation induction is carried out by Human menopausal gonadotropin, urinary FSH and recombinanat follicle-stimulating hormone which are equally effective. The use of gonadotrophin therapy for ovulation induction is associated with risk of ovarian hyperstimulation and multiple pregnancy (1). 

Intracytoplasmic sperm injection should be considered if  a previous IVF cycle has resulted in failed or poor fertilization. This improves fertilsation rates compared to IVF but once ferltilisation is achieved the pregnancy rate is no better than with in vitro fertilisation.

(b) Discuss the steps you would take to minimize the risk of major complications associated with the treatment of this couple?

The major complications associated with ther treatment of this couple are multiple pregnancy with its associated complications. ovarian hyperstimulation and  risk of pelvic infection due to uterine instumentation. List should be in your answer plan

Multiple pregnancy  is  associated with increased perinatal mortality  . Ultrasound monitoring of follicular activity and adjusting the dose of clomiphene can minimise the risk of multiple pregnancy (1).

The transfer of no more than three embryos according to HFEA guidelines not what the guidelines say!!!  minimises the risk of high order muliple births.

. Ovarian hyperstimulation syndrome Identification of Another major complication is ovarian hyperstimulation syndrome ( OHSS) . OHSS is characterised by ovarian enlargement, increased vascular permeability and fluid shifts. Mainly seen during ovulation induction by gonadotrophins.

Prediction of OHSS is important in preventing OHSS such as identifying some patient characteristics like young age , low body weight and previous OHSS which are associated with developing OHSS low BMI, PCO.  Cautious administration ovulation induction regimen such as  low doses of FSH  is appropriate for them (1). of Mon-follicular ovulation induction using gonadotrophin in a chronic low dose step-up regimen carries a lower risk of over- stimulation WILL YOU USE THIS FOR IVF?. 

For oocyte maturation, use of gonadotrophin antagonist rather than agonist is associated with reduced risk of OHSS.

In case of excessive ovarian response due to gonadotrophins, coasting (1) is associated with reduced riks of OHSS. Coasting is stopping the gonadotrophin injection while continuing pituitary suppression. Lacks evidence from randomised studies. Do the other strategies you suggest have evidence from RCTs? Coasting for more than 3 days is associated with reduced pregnancy rate. 

Single embryo transfer, blastocyst transfer and elective cryopreservation also reduce the risk of OHSS (1).

Providing luteal support with progesterone which is as effective as HCG also reduces the risk of OHSS.

In the presence of excessive ovarian response, cancellation (1) of the cycle may be considered to avoid late OHSS but the risk of early OHSS is uneffected. Elective cryopreservation is an alternative to cancellation of the cycle.

For minimising the risk of pelvic infection at the time of egg collection no touch technique of the catheter tip should be used.  Before undergoing uterine instrumentation during IUI, egg collection or embryo transfer,she should be offered screening for chlamydia screening using NAAT testing of endocervical swabs or urethral samples to facilitate antibiotic prophylaxis (1). 

a)The lack of identifiable reason for unexplained infertility makes the treatment empirical.?? meaning Conservative management, ovulation induction  with or without IUI, IVF-ET are the main approachesin the management of unexplained infertility. I will tell her that  approximately 60% of couples with unexplained infertility will conceive within 3 year . In this treatment there is no risks except waiting period , however results are less good with primary infertility so what are the results? 59% or 5%???.While considering this option woman’s age has to be considered , as in her case this can be a suitable one.Results of IUI are not better than conservative management (1) . It is not expensive but need to collect and to insert timely ? meaning.Ovulation induction with clomiphene citrate  with timed sexual intercourse can also be tried but results are not better than conservative managemaent (1), but instead carries the risks of multiple pregnancy (1) and OHSS .The cumulative pregnancy rate of COS??? with gonadotrophins and IUI is  around 40% over 1 or 10 years??? but the benefit of IUI over timed sexual intercourse  is there a role for times intercourse in managing infertile couples?? is controversial and firm evidence is lacking. This option which option are you writing about??? is less stressful, less physically demanding , less  expensive  and better pregnancy rate. IVF-Et is the last resort why should this be the last resort??? . It is  expensive no it is not and cost is not the only consideration in healthcare. The cost of 3 COS –IUI  cycles is comparable to 1 IVF what are the pregnancy rates? If pregnancy rates for 1 IVF cycle are higher than for 3 COS-IUI (whatever that is) then IVF is more cost-effective. It provides   detailed information of fertilized ovum and the embryo before implantation. You need to write simple sentences with a clear subject

b) The Risks of OHSS can be prevented by identifying the high risk woman like young age , low BMI, Previous OHSS and history of PCOS PCO – this woman does not have PCOS and avoiding high doses  of Gonadotrophins (1) and using    gonadotrophins  antagonist .Close follicular tracking to be done to monitor the growth  and to avoid HCG injection  if high estradiol level (1). To  abandone the  embryo transfer and cancel the ivf ycles ,or to freeze the embryo (1) and later transfer when the estradiol levels are reduced to < 13000 pmole/l. This will reduce the severity of OHSS but not its incidence.  During oocyte retrieval  there is risks of visceral injuries , bleeding and infection and this can be minimized  if procedure is carried by experienced and  skilled person , approaching by transvaginal route under ultrasound guidance and antibiotic cover (1).Multiple pregnancies are associated with  serious maternal morbidity ,perinatal morbidity and mortality . To reduce the risks of multiple pregnancy  U.K. legislation and guidance has restricted  the number of embryo transfer to two (1) except in woman > 40 years where maximum  3 can be transferred. Selective single embryo transfer  for selected good prognosis  patient (1)  is  recommended by the HEFA. If  high order multiple birth occurred ,every effort should be made to do selective reduction and minimizing multiple pregnancy  but this carries psychological and financial issues what are the financial issues???  Risks of ectopic  pregnancy can be reduced by  selective fallopian tube clipping and salpinghectomy in a woman with unexplained infertility? and early scan and follow up .Risks of miscarriages can be reduced with progesterone  support in luteal phase due to suppressed  LH bydown regulation . Risks of anxiety and psychological  issues can be best minimized by good team   effort  , support groups and  providing   information leaflets.

a.        

a. Treatments include expectant management, which is associated with up to 92% live birth rate in women of this age, after 3 years of trying to conceive so if you do nothing, this couple have a 92% chance of having a baby in the next year or two?. This is unpredictable but is safe and cost effective, in the absence of pathology. It is however associated with continued anxiety for the couple.

Six cycles of Intrauterine insemination is a suitable alternative. This improves pregnancy rate in such couples no it does not and is recommended not recommended – see draft revised NICE guidelines. It is cheaper than IVF, and carries minimal risks for the couple. Intrauterine deposition is preferred to intracervical deposition of semen. Pregnancy may be improved further by intrafallopian introduction of semen.  Couples should ideally be screened for STI eg Chlamydia, Hep B, HIV rubella immunity  prior to undergoing assisted reproduction, and vaccinated for rubella at least one month prior to attempting conception, and Hep B vaccination.

A further alternative is ovulation induction using antiestrogens clomiphene citrate or tamoxifen what is the success rate? EVALUATE  This carries the risk of OHSS and multiple pregnancy (1), and follicular tracking by ultrasound is recommended at least for the first cycle to gauge ovarian response. Serum estrogen is not recommended for follicular tracing as it is nonspecific and less accurate. In addition the lowest efficacious dose of clomifene/tamoxifen is recommended to reduce the risks of OHSS and multiple pregnancy.

IVF is an alternative for unexplained infertility. It is however expensive this couple will not have to pay for treatment, has a high failure rate does it? What is the failure (or success rate) and how does this compare to doing nothing / IUI? Where have you seen outcomes of fertility treatments being quoted as failure rates???, carries a risk of OHSS, multiple pregnancy  and is stressful for the couple compared to doing nothing?.  Three cycles of IVF is recommended for a given couple and a live birth rate of about 25-30% per cycle or for the 3 cycles? Why limit to 3 cycles? can be expected for this couple.  

An alternative such as adoption (1) may be suitable for some couples. This can however be very stressful, and carries reduced satisfaction rates ? evidence.

b.To minimise the risk of stress I will arrange for professional counselling for the couple prior to and during the period of treatment.

To reduce the risk of OHSS I will use unstimulated cycles for IUI. For ovulation induction with clomifene or tamoxifen I will use the lowest efficacious dose, accompanied by ultrasound follicular tracking (1) for, at least, the first cycle, to reduce the risk of OHSS. I will gradually increase the dose in the absence of ovulation till an efficacious dose is reached. Similarly during IVF I will use the lowest efficacious dose (1) of HMG, urinary-FSH or recombinant FSH starting from a low dose and gradually increasing it to achieve ovulation and minimise OHSS.

I will ensure egg collection is performed under ultrasound guidance to reduce the risk of vascular, bowel or other organ injury.

Where there is overwhelming ovarian response I will consider cycle cancellation (1), coasting, freezing the embryo for delayed transfer to minimise OHSS (1) more detail needed. I will use progestogen rather than HCG for luteal phase support, particularly where ovarian response has been excessive to reduce OHSS risk.

Multiple pregnancy is associated with increased risks of miscarriage, prematurity, growth restriction, perinatal mortality, and maternal complications eg anaemia, preeclampsia and caesarean delivery. I will consider single embryo transfer (1) which reduces the risks associated with multiple pregnancy as well as OHSS. I will freeze any extra embryos for future needs, to reduce the need for repeated ovarian stimulation and associated risks of OHSS and multiple pregnancy.

I will ensure up to date cervical cytology to reduce the risk of delayed diagnosis of cervical precancer and /or cancer what has this got to do with infertility?.

I will ensure testing of immune status for rubella, Hep B, and HIV screen to allow for vaccination and treatment, as appropriate. I will offer STI screening ,including Chlamydia , and treatment if positive, to reduce the risk of ascending infection during pelvic and uterine instrumentation.

I will ensure folic acid supplementation preconception and up to 12 weeks gestation to minimise the risk of NTDs.

A ] The treatment options are life style modification such as avoidance of smoking , alcohol intake and consumption of caffiene . the female should avoid Nsaid is this a treatment? . this improves rate of fertility . if she is obese weight reduction will have good out come did the question say she was obese / smoker?? Healthy woman. The husbands occupation is also important, if he is working in place where there is increase in temperature this will effect his testes and decrease the sperm quality NO CAUSE HAS BEEN FOUND!!!. tell the patient to take prepregnancy folic acid and check her rubella status and immunise if not immune . The success rate also depends on the age of the patient , it is better in patient between age group 23-35 yrs JUST ANSWER THE QUESTION ASKED – YOU ARE GIVEN THE WOMAN’S AGE compared to a older patient . successful also if she has previous children READ THE QUESTION!!!. Take history about frequency of coitus , she should have regularl coitus  every 2-3 days . in case of This suggests you have not read the question – unless you read the question and take account of every bit of information in it, you have no chance of writing a good answer unexplained infertility she can be  take clomifene citrate for stimulation of her ovaries up to 6 cycles .this helps ovulation she has no problems with ovulation and  results in pregnancy but risk of multiple pregnancy and OHSS. she needs follicular  tracking atleast for the first cycle by USG . if this is not successful then stimulation of the ovaries with clomifene citrate and timed intercourse but this increases the patients anxiety. if she is resistant to clomifene citrate she is ovulating  then she can have laproscopic ovarian drilling . this is helpful in female with PCOS , where her LH level  is decreased and results in pregnancy not relevant to this woman. the risk of multiple pregnancy and OHSS is not there and there is no need of follicular tracking  . patient has risk of exposure to anaesthetia and surgery . there is risk of damage to viscera and blood vessels . if the patient is ovulating what does the question say?she can have simple method of IUI or if she is not ovulatig she can have ovarian stimulation and IUI . success rate is about 20% per cycle but it causes patient anxiety .the other option is gonadotrophin stimulation of the ovaries and use of HMG or recombinant FSH or urinary FSH for luteal support but risk of ectopic pregnancy , multiple pregnancy and OHSS . she needs follicular tracking . other option is she can go for IVF where there is down regulation of the pitutary by gonadotrophins and give HMG or follicular/urinary FSH for luteal support but risk of multiple pregnancy , ectopic and OHSS . there is risk even at oocyte retrival by damage to viscera , bleeding and introduction of infection . this procedure is costly and not part of NHS especially if they have previous children . she can go for ICSI but risk of genetic abnormality and needs genetic councelling . other option is they can go for adoption but needs adequate councelling of the whole family including other children in the family . sometimes good emotional and psychological support is enough to achieve pregnancy . provide information leaflet and help from support group . you have not answered the question that you were asked.


B] The steps taken to minimise the risk of IVF are as follows . minimal risk are avoided by , Adequate councelling  the couple  who  is going for IVF poor English. discuss there benefits ,risk and  other available  options .provide information leaflet before hand . the couple needs to be seen in a dedicated fertility clinic where there is  protocol to avoid , diagnose and treat OHSS . the patient selection is atmost important   young patient ,who is not obese and who has modified her life style such as avoidance of alcohol, smoking improves the outcome you were asked about minimizing risks .the couple is screened for HIV, HEPB ,if positive councel the couple about the implication of the infection  on the children . the major complications are minimised by. THIS IS WHAT YOU WERE ASKED ABOUT and you have wasted 25% of your time & space   if there is evidence of hydrosalphix laproscopic salphingectomy should be done answer the question asked: THIS COUPLE – unexplained infertility – how can there be tubal disease???. when there is evidence  of OHSS cancel the cycle  (1) and freeze the embryos for the use in next cycle  . the purpose of this is to avoid ovulatory trigger by Hcg (-1) you lose a mark because you do not understand what you have written – if you do not trigger ovulation, where do you get embryos to freeze?. by doing this  the risk of ovarian stimulation and oocyte retrival in the next cycle  is minimised . stimulation of the ovaries with antiestrogen clomifene citrate but may be ineffective . down regulation  of pitutary is done by low dose gonadotropin agonist  and HMG , giving in pulsatile fashion HOW??? decreases the rate of OHSS   .  follicular tracking is done by USG for early identification of OHSS and early intervaention  . coasting (1) is done if there are more number of follicles seen  discontinue gonadotropin and delaying luteal support with HCG or urinary/follicular FSH .reducing the number of oocytes recovery may compromise the pregnancy ? so are you going to let her have OHSS instead? FIRST DO NO HARM. instead of using HMG or urinary/recombinant FSH  for luteal support  , luteal support can be provided with progesterone . routiene use of HMG for luteal support is not indicated . prophylactic use of albumin or HES at the time of oocyte retrival .? evidence follicular aspiration can be done but risk of damage to surrounding viscera and introducing infection .follicular flushing is not needed if about 3 follicles are there . trained ,experience person should do oocyte retrival as risk of haemorrhage, trauma and introducing infection in the pelvis . consious sedation analgesia must be used at the time of oocyte retrival . not more than two embroys must be implanted transferred according to rcog  guidelines  and usg guided implantaion transfer with the endometrial thickness more than 5mm is needed for improved success rate . rest of not more than 20 mins is needed after embroy implantation . the patient must be councelled if she has any abdominal pain or distention she should report to the hospital . provide her 24 hr hospital contact number.  early identification and prompt treatment of OHSS improves the outcome .  

A healthy 30 year old woman and her healthy 37 year old partner are attending the fertility clinic because of a 3 year history of primary infertility. Following full investigations, no cause has been identified. (a) Critically evaluate the available treatment options [8 marks]. (b) Discuss the steps you would take to minimize the risk of major complications associated with the treatment of this couple [12 marks]. A) Treatment options of unexplained infertility are expectant management.ovulation induction by antiestrogen like clomiphen citrate or Tamoxiphen.and assissted reproductive techniques (ART). This list should be in your answer plan not in your answer. There are no marks for writing a list expectant management trough councelling the couple about increment of cumulative pregnancy rate with it what is it? .advice about decrease weight if BMI >30 to gain weight if BMI <18 and stop smoking increase spontenous pregnancy rate.Timed intercourse is not recommended as it is associated with increase anxiety.however.expectant management associated with decrease satisifaction and increase anxiety of the couple (1). Ovulation induction with antiestrogen such as clomiphen citrate or Tamoxiphen can be tried but it is associated with side effects of the drugs such as headach ,visual disturbances,abdominal pain and hot flush.moreover it is associated with risk of ovarian hyperstimulation syndrome and multiple pregnancy (1) does it increase pregnancy rates?. IUI is more effective than no treatmet not true and it can be used with stimulated or unstimulated cycle.But for these couple unstimulated cycle is recommended as it is associated with decrease risk of multiple pregnancy or hypestimulation syndrome.also it is more cost effective.IIUI can be used for 6 cycles. IVF is another option and can be tried for up to 3 cycleswhy not more than 3? What s the success rate? EVALUATE. IVF associated with risk of ovarian hyperstimulation syndrome and multiple pregnancy (1) and it is expensive she will no have to pay for her treatment. Treatment for cancer is expensive – is that a disadvantage of treatment?. lastly adoption (1) may be telast resort but it carries more anxiety ? evidence and low satisfication. B)one of theMajor complictions of treatment option is Ovarian hyperstimulation syndrome (OHS).this can occured with ovarian stimulation by gonadotrphin agonist in IVF cycle and to lesser extent with clomiphen citrate.Coasting (1) through holding of gonadotrophin injection leads to atrophy of small and intermediate follicle while.large follicle contine to grow. usage of gonadotrophin antagonist provide suppression of endogenous gonadotrophin release without impairing pitutary senstivity to GnRH.luteal phase support with progeterone instead of HCG decrease risk of OHS. Canellation of the cycle and freezing of the embryo is another option (1). multiple pregnancy caries high risk of perinatal morbidity and mortality ad can be decreased through usage of unstimulated IUI.In IVF HFEA recommendes no more than 3 embryoes transfereno more than 2 in women aged < 40 years and RCOG recommendes no more than 2 embruo transfer. In OOcyte retrieval there is isk of intraabdominal haemorrage 0.4% infection 0.2% and injury of ovarian tissue.expirenced obstetrician and antibitics can reduce it. Ovarian Torsion can happened with hyperstimulatied ovaries manifested by sudden sever abdominal pain with nausea and vomiting.early diagnosis of it and untwisting through laparoscopy or laparotomy can perserve the ovaries. there is increase risk of Ectopic pregnancy with ART and needs early dignoses and treatment . there ar long term risk of ovarian cancer .Rcog recommendes 12 months of clomiphen citrate to decrease this risk. the couple need psychological support to minimize risk of psycological morbidity.

The couple seem why seem? What else could it be? to have Unexplained Infertility and they should be dealt with in a sensitive manner.No treatment and offering expectant management are these different?would not relieve their anxiety. How likely is this to succeed? Lifestyle modifications like weight reduction,avoid smoking,alcohol ,recreational drugs can be suggested as an adjunct to improve treatment success rates healthy couple.Available options are ovulation induction using Clomiphene citrate, Intrauterine insemination(IUI) , Invitro fertilisation(IVF)    and Intracytoplasmic sperm injection(ICSI) the last two being ART(ASSISTED REPRODUCTIVE TECHNIQUES).Folic acid prophylaxis 0.4mg,screen for HIV,Hbsag,rubella immunity before treatment. Are these treatment options?

    OI ??? with clomiphene can be tried for 6 cycles with ultrasound monitoring for follicular maturity,success rates upto 40%. How does this compare with doing nothing? But risk of multiple pregnancy 6 to 12% and endometrial thinning why is this a risk? .Use beyond 12 cycles increases risk of ovarian cancer. IUI is another option can be tried for 6 cycles.Avoiding clomiphene  before IUI minimises chances of multiple pregnancy  called “Unstimulated cycle” what is the success rate? EVALUATE .FALLOPIAN SPERM PERFUSION is a technique in IUI using lot of perfusion fluid with the sperms,giving better success rates WHAT IS THE RATE?. IVF is a costlier alternative,not funded by the NHS if the couple have children previously does this couple? .Can be offered for 3 cycles why only 3? with success rates of 20% for this couple (1).It involves downregulation of the womans ovaries using GnRH agonists,ovulation induction with gonadotrophins,oocyte  retrieval,sperm collection, IVF and embryo transfer(not more than 3 as per HFEA Guidelines). If there is a problem in fertilisation ICSI can be offered but if male partner has y chromosome abnormalities,genetic counselling is required.If risks of genetic problems Donor sperms an option as per British Andrology Society  Guidelines.     

           Problems associated with treatment  are Ovarian hyperstimulation syndrome OHSS mild in 33% moderate to severe in 6 to 8%.increased risk if polycystic ovaries,formation of >20 follicles ,multiple pregnancy .Enlarged ovaries prone for torsion,may need emergency surgery for undoing torsion .OHSS can be prevented by identifying risk factors (1),using minimum doses of gonadotrophins required for successful ovulation (1),avoiding HCG injection and avoiding further gonadotrophins if >20 follicles on scan or serum estradiol >12000 pg/ml called COASTING this is not coasting – you are cancelling the cycle.Risk of multiple pregnancy in IVF can be minimised by following HFEA Guidelines of not >3 embryos transfer no more than 2 in women < 40 years or not >2 as per the RCOG .IUI with unstimulated cycle also minimises multiple pregnancy risks.Problems with oocyte retrieval are pain,can be done under sedation as per RCOG guidelines,infection0.2%,intraperitoneal bleed0.4%,injury to viscera minimised if done by skilled personnel.Risk of ectopic pregnancy 6% can be minimised by surgical removal of hydrosalpinx if present ,also improves success rates in IVF.Miscarriage rates can be minimised by avoiding embryo transfer if endometrium is thin and supporting pregnancy with progesterone ,HCG if gonadotrophins were used in induction .Psychological morbidity to couple in case if treatment fails,or complicatons occur has to be dealt with by trained counsellors.Most important would be to offer information leaflets to couple and website details like www.nhsdirect.nhs.ukas ,involving them in decision making contributes to treatment success. 

a) this is unexplained infertilty.I'd be sensitive and empathetic as unexplained cause gives more pshycological stress to the couple. I'll explain to them that they have a good chance (90%) do they? Over what period of time? 1 month? of spontaneous conception with conservative/expectant management like regular(every alternate day) intercourse,healthy lifestyle(reduce achohol,avoid smoking, exercise),avoid NSAIDS particularly around ovulation(midcycle).But this maynot be acceptable to them as they have been trying for 3 years (1).

the other option would be to offer medical management by offering ovulation induction. it has been shown that pregnancy rate may improve with ovulation induction in unexplained infertility by increasing the chance of fertilisation. How does this happen given that there are no problems with ovulation? this can be combined with timed intercourse or intra-uterine insemination. this means more medicalisation , increases anxiety why should treatment increase anxiety?, and needs more monitoring(regular ultrasounds for follicular development ),increases risk of ovarian hyperstimulation,multiple pregnancy (1), hospitalisation.

if that fails, there is the option of IVF. The low implantation rate of 25% -30% so 20-30% per cycle is low – what is the spontaneous pregnancy rate per cycle in a fertile couple? Is 20-30% implantation rate? How do you diagnose implantation? should be explained. the risk of multiple pregnancy, heterotopic pregnancy(uterine and ectopic pregnancy),ovarian hyperstimulation (1) should be discussed in detail. the option of adoption (1) would also be discussed sensitively.

b)-the major complications of treatment in this couple are ovarian hyperstimulation(OHSS), multiple pregnancy, ectopic pregnancy, miscarriage,increased morbidity, hopsitalisation, psychological stress for both partners. Do not write a list I'd offer detailed discussion regarding the benefits and risks associated with the options of treatment available to them. help them with written information, provide contact numbers of counsellors, and advice about support groups.

if using ovulation induction, try with clomiphene citrate first before going on to GnRH analougues as less risk of OHSS, multiple pregnancy with clomiphene. if using GnRh analougues, would offer long antagonist cycle(less flare symptoms).Inform,provide written information about signs and symptoms of OHSS, Ectopic pregnancy, for early diagnosis and management. Offer early ultrasound for fetal viability, location. Offer progesterone support in early pregnancy to reduce risk of miscarriage(not evidence based). You have not gone on to discuss how the risk of the complications listed can be minimised