Subfertility V1

<h4>Dear all future doctors, welcome to Taylor's Fertility Center</h4> Sit back, relax and click [[here|story]] to start. <img src="/Subfertility/cartoon.jpg" />

36-year-old Ms Violet has been married to 32-year-old Mr Kim for 8 years. They do not not have any children. She has been trying to get pregnant for the past 6 years. How do you define a couple as subfertile? I am sure this is easy peasy lemon squeezy for you. <img src="/Subfertility/bench.jpg"/> [[1. Subfertility is defined as the failure to conceive within 6 months of unprotected regular sexual intercourse.]] [[2. Subfertility is defined as the failure to conceive within 1 year of unprotected regular sexual intercourse.]] [[3. Subfertility is defined as the failure to conceive within 1.5 years of unprotected regular sexual intercourse.]] [[4. Subfertility is defined as the failure to conceive within 2 years of unprotected regular sexual intercourse.]]

No, no... 6 months is still too soon to be concerned. Go back and try again (track: 'Baby Giggle 1', 'play') (track: 'Baby Giggle 1','volume', 0.4)

Excellent! You are good. People who are concerned about their fertility should be informed that over 80% of couples in the general population will conceive within 1 year if: • the woman is aged under 40 years and • they do not use contraception and have regular sexual intercourse. Of those who do not conceive in the first year, about half will do so in the second year (cumulative pregnancy rate over 90%) Now, climb another step to solve some more issues. [[Let's go.|stair]] (track: 'one cheer', 'play') (track: 'one cheer','volume', 0.4)

No, no. People who are concerned about their fertility should be informed that over 80% of couples in the general population will conceive within 1 year if: • the woman is aged under 40 years and • they do not use contraception and have regular sexual intercourse. Of those who do not conceive in the first year, about half will do so in the second year (cumulative pregnancy rate over 90%) Go back and try again (track: 'Baby Giggle 1', 'play') (track: 'Baby Giggle 1','volume', 0.4)

Hey, don't look back...Click on the picture to keep going. [[<img src="/Subfertility/stairs.jpg" >->causes]]

For the next step, you need to think of all the possible causes of subfertility in this couple. Choose whichever of the following causes you think is possible: [[1. Male factors]] [[2. Ovulation disorders]] [[3. Iron deficiency anaemia]] [[4. Endometriosis]] [[5. Tubal factor]] [[6. Folic acid deficiency]]

Yay...you are right. The main causes of subfertility are: 1. Ovulation disorders 2. Male factors 3. Tubal damage 4. Endometriosis and fibroids 5. Unexplained Now, you are a step closer. [[Let's go.|history]] (track: 'happykids', 'play') (track: 'happykids','volume', 0.5)

Right! The main causes of subfertility are: 1. Ovulation disorders 2. Male factors 3. Tubal damage 4. Endometriosis and fibroids 5. Unexplained Now, you are a step closer. [[Let's go.|history]] (track: 'happykids', 'play') (track: 'happykids','volume', 0.5)

Ohh nooo... Iron deficiency anemia could cause adverse effects in pregnancy once they are pregnant. However, iron deficiency anemia per se won't normally affect fertility. Try again. (track: 'oh no', 'play') (track: 'oh no','volume', 0.4)

You are doing good! The main causes of subfertility are: 1. Ovulation disorders 2. Male factors 3. Tubal damage 4. Endometriosis and fibroids 5. Unexplained Now, you are a step closer. [[Let's go.|history]] (track: 'happykids', 'play') (track: 'happykids','volume', 0.5)

Correct! The main causes of subfertility are: 1. Ovulation disorders 2. Male factors 3. Tubal damage 4. Endometriosis and fibroids 5. Unexplained Now, you are a step closer. [[Let's go.|history]] (track: 'happykids', 'play') (track: 'happykids','volume', 0.7)

That's incorrect. You may have heard that folic acid deficiency has adverse effects on pregnancy such as neural tubes defects. Women intending to become pregnant should be informed that dietary supplementation with folic acid before conception and up to 12 weeks' gestation reduces the risk of having a baby with neural tube defects. The recommended dose is 0.4 mg per day. For women who have previously had an infant with a neural tube defect or who are receiving anti-epileptic medication or who have diabetes, a higher dose of 5 mg per day is recommended (NICE guidelines NG3). However, folic acid deficiency per se will not affect fertility. Try again ;-) (track: 'oh no', 'play') (track: 'oh no','volume', 0.5)

You have already thought of possible causes of their fertility problems. Based on that, what kind of questions would you like to ask Ms Violet and Mr Kim? Note, there may be more than 1 correct answer. [[1. History and lifestyle including use of alcohol, smoking and recreational drugs only for Mr Kim]] [[2. History of previous pregnancies with previous marriage only for Ms Violet]] [[3. Details of coital frequency and any difficulties with coitus]] [[4. Detailed menstrual history]]

Ohhh nooo. History and lifestyle including use of alcohol, smoking and recreational drugs should be asked of BOTH Mr Kim and Ms Violet. Alcohol for Women: Drinking no more than 1 or 2 units of alcohol once or twice per week and avoiding episodes of intoxication reduces the risk of harming a developing fetus. Alcohol for Men: Alcohol 3 to 4 units per day is unlikely to affect their semen quality but excessive alcohol intake is detrimental to semen quality. Smoking for Men and Women: Smoking is likely to reduce their fertility & reduced semen quality. Try again. (track: 'no dear', 'play') (track: 'no dear','volume', 0.4)

No, dear. History of previous pregnancies with any previous marriage should be asked of BOTH Mr Kim and Ms Violet. Try again. (track: 'no dear', 'play') (track: 'no dear','volume', 0.4)

Hooray! That's right. Coital frequency: Sexual intercourse every 2 to 3 days optimises the chance of pregnancy. Alcohol for Women: Drinking no more than 1 or 2 units of alcohol once or twice per week and avoiding episodes of intoxication reduces the risk of harming a developing fetus. Alcohol for Men: Alcohol 3 to 4 units per day is unlikely to affect their semen quality but excessive alcohol intake is detrimental to semen quality. Smoking for Men and Women: Smoking is likely to reduce their fertility & reduced semen quality BMI for Men and Women: Body Mass index (BMI) of 30 or over take longer to conceive. Women who have a BMI of less than 19 and who have irregular menstruation or are not menstruating should be advised that increasing body weight is likely to improve their chance of conception Tight underwear in Men: There is an association between elevated scrotal temperature and reduced semen quality, Occupation for Men & Women: Some occupations involve exposure to hazards that can reduce male or female fertility and therefore a specific enquiry about occupation should be made and appropriate advice should be offered. You have been promoted! [[Click here.|door]] (track: 'Bingo', 'play') (track: 'Bingo','volume', 0.4)

An exciting journey awaits you! Click on the picture to proceed. [[<img src="/Subfertility/bridge.jpg" >->exam]]

What kind of relevant assessments would you like to do for Mr Kim and Ms Voilet regarding their issue of fertility? Note, there may be more than 1 correct answer. [[1. Neurological assessement for both Mr Kim and Ms Violet]] [[2. Pelvic examination for Ms Violet]] [[3. Opthalmological examination for Mr Kim]] [[4. Scrotal examination for Mr Kim]]

No, no. That is not very relevant in this case. Try again ;-) (track: 'sad', 'play') (track: 'sad','volume', 0.4)

Excellent. General examination to assess both partners' height, weight, and BMI should be done. Systemic examinations including abdominal examination for both partners should be carried out. An examination of both partners is essential to ensure normal reproductive organs. For males, the examination must assess testicular size as well as exclude testicular masses, congenital absence of the vas deferens, and varicocele. Small testes may be associated with primary testicular failure. Click <a href = "https://maleinfertility.org/understanding-male-infertility/fertility-evaluation/physical-evaluation" target="_blank">here</a> for further reading on evaluation of male subfertility. For females, a full general and pelvic examination should be carried out to check for any endocrine and gynaecological abnormalities. Ideally, each partner should be examined separately so that a confidential history regarding sexually transmitted diseases or previous pregnancies can be elicited. I am sure that you are already familiar with physical examination including BMI body mass index, abdominal examination, and pelvic examination. Click [[here|investigation]] to go to the next challenge. (track: 'lightapplause', 'play') (track: 'lightapplause','volume', 0.4)

No, no. That is not very relevant in this case. Try again ;-) (track: 'sad', 'play') (track: 'sad','volume', 0.4)

You're on your way to a sophisticated and wonderful adventure... Click on the jet to fly ahead. [[<img src="/Subfertility/Jet.jpg" >->tests]]

On physical examination, both Mr Kim and Ms Violet have unremarkable findings, except that Ms Violet's BMI is 32 kg/m2. You should order relevant investigations for both of them. The following are choices of investigations and their indications: <li>(A) To check ovulation: Measure Day 21 progesterone level </li> <li>(B) To check tubal patency: Measure basal body temperature </li> <li>(C) To check Ovarian reserve: Measure antimullerian hormone, follicular stimulating hormones </li> <li>(D) To test characteristics of a male's semen and the sperm contained therein: Semen analysis & repeat 2 weeks later if it is abnormal </li> The correct matching statements are: [[1. A and B]] [[2. A and C]] [[3. C and D]] [[4. B and C]]

Uhh ohh. Ok let's look at A and B again. (A) To check ovulation: Measure Day 21 progesterone level (B) To check tubal patency: Measure basal body temperature Answer A is perfect. But for answer B, to check tubal patency, we need to do a Hysterosalpingography/hysterosalpingo-contrast-ultrasonography/ laparoscopy and Dye test. Try again :-) (track: 'smirk', 'play') (track: 'smirk','volume', 0.4)

Perfect! Read the following table carefully, then click on the table to move to the next section. [[<img src="/Subfertility/AFP etiology evaluation subfertility.jpg" >->treatment]] (track: 'clapping', 'play') (track: 'clapping','volume', 0.4)

No, dear. Your choice is only 50% correct. Let's look at C and D again: (C) To check Ovarian reserve: Measure antimullerian hormone, follicular stimulating hormones (D) To test characteristics of a male's semen and the sperm contained therein: Semen analysis & repeat 2 weeks later if it is abnormal C is correct. However, for D, Semen analysis; the test is right but if it is not normal, we need to wait at least three months before repeating the test because spermatogenesis takes approximately 120 days. It is ok, go back and try again ;-) (track: 'smirk', 'play') (track: 'smirk','volume', 0.4)

Oh, no. Look at B and C again. (B) To check tubal patency: Measure basal body temperature (C) To check Ovarian reserve: Measure antimullerian hormone, follicular stimulating hormones C is correct. However, B is wrong. To check tubal patency, we need to do a Hysterosalpingography/ hysterosalpingo-contrast-ultrasonography/ laparoscopy and Dye test. Never mind, Try again ;-) (track: 'smirk', 'play') (track: 'smirk','volume', 0.4)

So far so good! Now you have to face a few challenging scenarios. Click on Scenario 1 first. <div class="row"> <div class="column"> Scenario 1: Ocean Pearls [[<img src="/Subfertility/pearlsx.jpg" alt="Pearls" style="width:100%">->Ocean pearls]] </div> <div class="column"> Scenario 2: Flowers Mystery [[<img src="/Subfertility/gardenx.jpg" alt="Flowers" style="width:100%">->unexplained]] </div> <div class="column"> Scenario 3: Butterfly Bravery [[<img src="/Subfertility/butterflyx.jpg" alt="Butterfly" style="width:100%">->Male factor]] </div> </div>

What INITIAL advice would you give this couple to help them successfully conceive? [[1. Timed sexual intercourse around fertility window]] [[2. Ovulation induction by ovarian drilling]] [[3. Ovulation induction by clomifene citrate]] [[4. Intracytoplasmic sperm injection (ICSI)]]

Oh nooo... Timed sexual intercourse is having sexual intercourse during the most fertile period (i.e. the six days preceding ovulation). Ms Violet has an ovulatory problem due to Polycystic ovary syndrome. Therefore, this method is not a suitable option for them. Try again. (track: 'evil laugh', 'play') (track: 'evil laugh','volume', 0.4)

No. Ovulation induction should not be offered as a first line treatment. The World Health Organization (WHO) classifies ovulation disorders into 3 groups: Group I: Hypothalamic pituitary failure (hypothalamic amenorrhoea or hypogonadotrophic hypogonadism) Group II: Hypothalamic-pituitary-ovarian dysfunction (predominately polycystic ovary syndrome) Group III: Ovarian failure Ms Violet's problem is considered a Group II ovulatory disorder. The recommended management is as follows: •   Adopting a healthy lifestyle and weight reduction may restore ovulation and improve their response to ovulation induction agents, and have a positive impact on pregnancy outcomes. •   Clomifene citrate or •   Metformin or •   Combination of both clomifene citrate and metformin If Ms Violet cannot conceive for six months with clomifene, the followings should be considered: •   Laparoscopic ovarian drilling or •   Combined treatment with clomifene citrate and metformin if not already offered as first-line treatment or •   Gonadotrophins Never mind, you can go back and try again. (track: 'evil laugh', 'play') (track: 'evil laugh','volume', 0.4)

Excellent. The World Health Organization (WHO) classifies ovulation disorders into 3 groups: Group I: Hypothalamic pituitary failure (hypothalamic amenorrhoea or hypogonadotrophic hypogonadism) Group II: Hypothalamic-pituitary-ovarian dysfunction (predominately polycystic ovary syndrome) Group III: Ovarian failure Ms Violet's problem is considered a Group II ovulatory disorder. The recommended management is as follows: •   Adopting a healthy lifestyle and weight reduction may restore ovulation and improve their response to ovulation induction agents, and have a positive impact on pregnancy outcomes. •   Clomifene citrate or •   Metformin or •   Combination of both clomifene citrate and metformin If Ms Violet cannot conceive for six months with clomifene, the followings should be considered: •   Laparoscopic ovarian drilling or •   Combined treatment with clomifene citrate and metformin if not already offered as first-line treatment or •   Gonadotrophins Now that you've successfully settled the couple's 'pearly' problem, it's time to face a different challenge. Return to the [[scenarios|treatment]] and choose Scenario 2 (Flowers Mystery). (track: 'Success', 'play') (track: 'Success','volume', 0.4)

That is incorrect. ICSI is considered for male-factor infertility. Mr Kim's results are all normal. So ICSI is not a good choice for this couple. Try again. (track: 'evil laugh', 'play') (track: 'evil laugh','volume', 0.4)

<h4>Scenario 1 (Ocean Pearls)</h4> On assessment of the couple, Mr Kim's results are perfect. But Ms Violet gives a history of irregular menstrual cycle, once in every 3-4 months for past 3 years. She has gained 10kg in the past 9 months too, associated with abnormal growth of facial hair. On examination, her BMI is 31 kg/m2, and hirsutism is noted. Her mid-luteal phase serum progesterone level is 10.2 nmol/L (normal >15.9 nmol/L) Her serum testosterone is 98 ng/dl (normal 6-86 ng/dl) Her pelvic ultrasound shows multiple small cysts in both ovaries. Click on Ms Violet's pelvic ultrasound picture showing her 'string of pearls'-like polycystic ovaries [[<img src="/Subfertility/UScysts.jpg" >->pcos]]

That is not true. Mr Kim's investigations are normal. This would have included a semen analysis. Therefore, he does not require donor sperm. Mr Kim will feel very disappointed if you suggested that! It is ok, try again. (track: 'Punch 2', 'play') (track: 'Punch 2','volume', 0.4)

Hey, that is right! IVF is recommended in women below the age of 40 years who have not conceived after 2 years of regular unprotected intercourse or 12 cycles of artificial insemination (where 6 or more are by intrauterine insemination). Offer her 3 full cycles of IVF, with or without ICSI. See the NICE guidelines about the assessment and treatment of fertility problems <a href="/Subfertility/NICE fertility-problems-assessment-and-treatment.pdf" target="_blank">here</a>. A typical IVF-embryo transfer cycle consists of the following steps: 1. Initial consultation 2. Pituitary down-regulation with either gonadotrophin-releasing hormone agonist or gonadotrophin-releasing hormone antagonists 3. Superovulation ovarian stimulation with either urinary or recombinant gonadotrophins 4. Ovulation trigger with hCG trigger 5. Oocyte collection 6. Insemination of oocytes 7. Embryo transfer: ultrasound-guided embryo transfer 8. Luteal support with progesterone 9. Pregnancy test See the chapter on subfertility from Gynaecology by Ten Teachers (18th edition) <a href="/Subfertility/Subfertility Gynaecology by 10 Teachers 18th Ed.pdf" target="_blank">here</a>. Great. You have successfully managed Scenario 2 and now it's time for yet another challenge. Return to the [[scenarios|treatment]] and select Scenario 3 (Butterfly Bravery) (track: 'Basic rock 135', 'play') (track: 'Basic rock 135','volume', 0.4)

No, no. Ms Violet's menstrual cycles are normal, and her investigation results are fine, which would've included mid-luteal progesterone levels. Therefore, she does not require ovarian stimulation with clomifene citrate. That's ok, try again. (track: 'Punch 2', 'play') (track: 'Punch 2','volume', 0.4)

Oh no. Ms Violet is a healthy lady with normal investigation results. Therefore, she does not require Laparoscopic adhesiolysis nor gonadotrophins. Try again. (track: 'Punch 2', 'play') (track: 'Punch 2','volume', 0.4)

<h4>Scenario 3 (Butterfly Bravery)</h4> For your final scenario, let's imagine that Ms Violet is completely healthy with no detectable medical issues. Mr Kim is healthy according to his history and physical examination. His semen analysis offers the following results: Semen volume: 1.6 ml pH: 7.32 Total sperm number: 32 million spermatozoa per ejaculate Total motility (percentage of progressive motility and non-progressive motility): 35% motile or 22% or more with progressive motility Vitality: 60% live spermatozoa Sperm morphology (percentage of normal forms): 4.2% What would you like to do at this juncture? [[1. Reassurance, saying that everything is normal]] [[2. Offer in-vitro fertilization (IVF)]] [[3. Offer intracytoplasmic sperm injection (ICSI)]] [[4. Repeat semen analysis in 1 month]] [[5. Repeat semen analysis in 2 months]] [[6. Repeat semen analysis in 3 months]]

<h4>Scenario 2 (Flowers Mystery)</h4> For this scenario, let's imagine that both 32-year-old Mr Kim and 36-year-old Ms Violet have no detectable medical issues. Both are fit and healthy and Ms Violet has a normal menstrual cycle. All their investigations are unremarkable. They have been married for 8 years now. They are identified as having unexplained infertility. How would you help them achieve a successful pregnancy? [[1. Donor insemination]] [[2. In-vitro fertilization]] [[3. Ovulation induction with clomifene citrate]] [[4. Laparoscopic adhesiolysis and start gonadotrophins]]

That is incorrect. Mr Kim has oligoasthenospermia. Repeat confirmatory tests should ideally be undertaken 3 months after the initial analysis to allow time for the cycle of spermatozoa formation to be completed. However, if a gross spermatozoa deficiency (azoospermia or severe oligozoospermia) has been detected, the repeat test should be undertaken as soon as possible. See the NICE guidelines about the assessment and treatment of fertility problems <a href="/Subfertility/NICE fertility-problems-assessment-and-treatment.pdf" target="_blank">here</a>. Don't worry, now you know :-) Try again. (track: 'error', 'play') (track: 'error','volume', 0.4)

Excellent. Mr Kim has oligoasthenospermia. Repeat confirmatory tests should ideally be undertaken 3 months after the initial analysis to allow time for the cycle of spermatozoa formation to be completed. However, if a gross spermatozoa deficiency (azoospermia or severe oligozoospermia) has been detected the repeat test should be undertaken as soon as possible. See the NICE guidelines about the assessment and treatment of fertility problems <a href="/Subfertility/NICE fertility-problems-assessment-and-treatment.pdf" target="_blank">here</a>. Here are the current World Health Organization (WHO) reference values: Semen volume: 1.5 ml or more pH: 7.2 or more Sperm concentration: 15 million spermatozoa per ml or more Total sperm number: 39 million spermatozoa per ejaculate or more Total motility (percentage of progressive motility and non-progressive motility): 40% or more motile or 32% or more with progressive motility Vitality: 58% or more live spermatozoa Sperm morphology (percentage of normal forms): 4% or more Click [[here|next step]] to proceed. (track: 'yess', 'play') (track: 'yess','volume', 0.4)

Three months later, Mr Kim's semen analysis shows a similar result of oligoasthenospermia. What will you advise to help them achieve a successful pregnancy? [[1. Varicocelectomy for Mr Kim]] [[2. Offer gonadotrophin to Mr Kim]] [[3. Intracytoplasmic sperm injection (ICSI)]]

Oh no. Not everything is normal. Mr Kim has oligoasthenospermia. Here are the current World Health Organization (WHO) reference values: Semen volume: 1.5 ml or more pH: 7.2 or more Sperm concentration: 15 million spermatozoa per ml or more Total sperm number: 39 million spermatozoa per ejaculate or more Total motility (percentage of progressive motility and non-progressive motility): 40% or more motile or 32% or more with progressive motility Vitality: 58% or more live spermatozoa Sperm morphology (percentage of normal forms): 4% or more It's alright, go back and try again. (track: 'error', 'play') (track: 'error','volume', 0.4)

Oh no. Although 25% of men with abnormal sperm parameters have a varicocele, there is no evidence that surgical ligation improves fertility. Try again. (track: 'yell', 'play') (track: 'yell','volume', 0.2)

No, dear. Men with idiopathic semen abnormalities should not be offered anti-oestrogens, gonadotrophins, androgens, bromocriptine or kinin-enhancing drugs because they have not been shown to be effective. Try again. (track: 'yell', 'play') (track: 'yell','volume', 0.2)

Correct! The recognised indications for treatment by ICSI include: •  Severe deficits in semen quality •  Obstructive azoospermia •  Non-obstructive azoospermia In addition, treatment by ICSI should be considered for couples in whom a previous IVF treatment cycle has resulted in failed or very poor fertilisation. Couples should be informed that ICSI improves fertilisation rates compared to IVF alone, but once fertilisation is achieved, the pregnancy rate is no better than with IVF. Well done. After you've watched the interesting video below, click [[here|final slide]]. <iframe width="560" height="315" src="https://www.youtube.com/embed/P27waC05Hdk" frameborder="0" allow="accelerometer; autoplay; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe> (track: 'bye bye', 'play') (track: 'bye bye','volume', 0.2)

<h4>You're a wonderful doctor!</h4> Because of your hardwork and compassionate care, Mr Kim and Ms Violet successfully conceived and delivered quadruplets. Believe it or not ;-), Mom and all four babies are well. The whole family are very grateful for your help and they wish you all the best for your upcoming EOY 4 exam. All references and recommended reading: 1. <a href="/Subfertility/Evaluation and Treatment of Infertility AFP.pdf" target="_blank">Evaluation and Treatment of Infertility (American Family Physician)</a> 2. <a href="/Subfertility/NICE fertility-problems-assessment-and-treatment.pdf" target="_blank">NICE guidelines on assessment and treatment of fertility problems</a> 3. <a href="/Subfertility/Subfertility Gynaecology by 10 Teachers 18th Ed.pdf" target="_blank">Subfertility chapter from Gynaecology by Ten Teachers (18th Ed)</a> 4. <a href = "https://maleinfertility.org/understanding-male-infertility/fertility-evaluation/physical-evaluation" target="_blank">Evaluation of male subfertility (external link)</a> <img src=/Subfertility/bunnies.png /> Back to <a href="https://medventure.neocities.org/Semester8/index.html">Home</a> (track: 'football', 'play') (track: 'football','volume', 0.5)

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