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Ten Reasons why You Should not Use Clomid for Fertility Treatment

Ten Reasons why You Should not Use Clomid for Fertility Treatment

Ten Reasons why You Should not Use Clomid for Fertility Treatment,

Not the Way your Using it Anyway

Ten Reasons why You Should not Use Clomid for Fertility Treatment, Not the Way your Using it Anyway. Clomiphene citrate (clomid) was the first medication introduced for fertility treatment (1960s). It works through masking of estrogen receptors in the brain. The brain, blind to estrogen in the blood, starts pouring FSH, the protein that drives development of dormant follicles in the ovary.

When one considers a fertility treatment: not only the pregnancy and delivery rates per cycle is considered, but also the time to conceive (TTC) and the complication rate especially multiple pregnancy. Clomid is a very attractive medicine to women and gynecologists, alike. It is an oral medication, easy to use for both general gynecologists and women seeking fertility treatment. It is also cheep. It is successful in inducing ovulation in 90% women that do not regularly ovulate e.g. polycystic ovary syndrome. Response to clomid is modest in most cases (1-2 follicles).

In spite of all these advantages, there are many other disadvantages. It, most likely, will not improve the odds of conception in regularly ovulating women. Its indiscriminate use, in The US and worldwide (without ultrasound monitoring of ovarian response), probably makes clomid the drug responsible for multiple pregnancies over all other forms of fertility treatment. Although clomid is successful in inducing ovulation in 80-90% of well selected patients, only 20% become pregnant. This discrepancy happens because of undesirable effects of clomid on the lining of the uterus (thin) and cervical mucus (thick). In my opinion though, many clomid cycles fail due to its in women that are not destined to benefit from it. Those are older and regularly ovulating women with unexplained infertility as opposed to suitable candidates: younger non-ovulating women. Clomid offers little help to women with unexplained infertility (ovulating) because in these women, the majority do not conceive because of chromosomal abnormalities in the eggs. Clomid commonly does not induce superovulation (many follicles) to partially compensate for abnormalities in the eggs.

Do Not Use Clomid Unless

1. Preconception labs are normal. Many patients are prescribed clomid without a complete fertility workup, including genetic screening. If you and your partner are carriers of cystic fibrosis or sickle cell anemia gene abnormalities, for example,you are at risk of transmitting these diseases to your future children (1:4). Genetic screening should be performed BEFORE starting fertility treatment. It does not help you to detect these abnormalities after pregnancy ensues. Decline clomid or any other fertility treatment without proper preconception history and lab tests.

2. Evidence of patent tubes. After ovulation induction, using clomid, the eggs has to be picked up by the fallopian tubes. Sperm also has to enter the fallopian tube to allow fertilization. Completely blocked fallopian tube may prevent the egg and sperm to meet. Partially blocked fallopian tube may allow fertilization but the the embryo may become stuck in the tube leading to ectopic pregnancy.

3. Near normal sperm analysis. A sperm concentration of < 15 million per mL and movement < 50% may reduce the odds for fertilization and reduce the chance of pregnancy after clomid treatment.

4. If you ovulate regularly. Together with normal sperm analysis and open tubes, that indicates you have unexplained infertility. The most likely cause for not conceiving is chromosomal abnormalities in the eggs. We cannot fix chromosomal abnormalities if the egg but we can induce the ovaries to produce more eggs. More mature eggs means more chance of producing a normal egg. Clomid induces the ovary to produce 1-2 eggs in most cycles, thus does not address effectively egg abnormalities. On the other hand, if you are young and do not regularly ovulate, clomid is able to induce ovulation and potentially solve your problem.

5. Without monitoring. Some women are more sensitive to the effects of clomid. They respond by producing a large number of follicles. The safest approach here is to cancel the cycle and restart another treatment with a lower dose. Although the risk of multiple pregnancy with clomid is about 10%, women that respond with producing a large number of follicles are at a much higher risk. Careful monitoring of response, using vaginal ultrasound, is required in all clomid cycles.

6. Use the lowest dose that leads to ovulation (start with one tablet per day). Do not increase the dose if ovulation took place at a lower dose. Most patients get pregnant at adoses of 50 to 150 mg (1-3 tablets) per day. Increasing the dose does not increase the chance for pregnancy and increases the side effects of clomid e.g thin endometrium, chick cervical mucus..

7. Do not use clomid more than 3 months (6 months life time max). The majority of women get pregnant in the first three months of treatment. If you are younger and ovulate on clomid and would like to try few more months, then 6 months is the maximum amount of time you should use clomid in your life time.

8. Clomid less likely to lead to pregnancy  delivery in women >38y. In women 38 or older with unexplained infertility, there is good evidence that clomid-IUI is inferior to IVF. The vast majority of women in that age group that start on clomid end up switching to IVF to achieve pregnancy.

9. Expertise with optimizing clomid cycles: clomid cycles should be supervised by a physician with expertise in clomid dosing, use of repeat courses, use of adjuvant treatments as estradiol and IUI. This enables maximizing the benefits of fertility treatment and tailoring treatment to individual woman.

10. Use letrozole before using clomid. Accumulating evidence from many studies, including randomized clinical trials, indicates that letrozole is superior to clomid in terms of achieving pregnancy. Applying the same principals above, letrozole should be considered as the initial treatment for anovulatory infertility.

On tailoring Fertility Treatment to Specific Patient’s Needs

In too many times, the use of clomid for fertility treatment is a stark example of tailoring patients to treatments familiar to general gynecologists, rather than individualizing fertility treatment to women biology and fertility needs, citing ease of use, perceived safety and familiarity. Cheep treatments that appear safe can quickly become aggressive and unsafe if they lead to low pregnancy rate and high multiple pregnancy. The time lost treating older patients with clomid for a prolonged periods can be detrimental to their ovarian reserve and can minimize the chance for eventually achieving pregnancy and delivery.

On men and clomid

There is no proof that men benefits from the use of clomid and similar treatment to improve sperm parameters. Specifically, there is no evidence that female partners of men that were prescribed clomid conceive at higher rates. With very few exceptions, clomid should not be used to treat male factor infertility.

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Fertility Treatment: Do not be Distracted

Fertility Treatment: Do not be Distracted

Fertility Treatment: do not be distracted by worthless recommendation

Fertility Treatment: do not be distracted by worthless recommendation

Fertility Treatment: Do not be Distracted

When contemplating options for fertility treatment with your own eggs, it always boils down to continue frequent intercourse, ovarian stimulation / ovulation induction + IUI or some form of IVF. During consultation or when weighing your options do not lose perspective of the big picture. Many suggestions may present themselves and serve to distract you. Men and Women load up on these distractions from the web, friends, primary care physicians or the couple themselves. Some of these recommendations are harmful because they shift the focus to non-proven interventions and most notably cause delay consultations with a reproductive endocrinologist and completing the infertility workup or starting treatment if needed.

Do not be distracted by these arguments

I am Healthy

Many women in America consider being healthy as being fertile. The media also bombard us with photos of beautiful women in their forties with babies. Truly many women, are in great shape with ideal body weight, exercise regularly, have no medical problems and feel great about themselves.

Fertility though speaks to a specific set of factors related to the ovaries, fallopian tubes and quality of sperm. Healthy women can have low egg reserve or blocked fallopian tubes or their partners have low sperm counts. Hence their fertility could be impaired. On the other hand, women not leading a healthy lifestyle or having a medical disorder can be very fertile if all fertility factors (tube, ovary, sperm) are functional.

I did not try enough

If you do not use birth control pills or condoms and you have having regular intercourse, then you are trying, irrespective of your conscious intentions. If you are you had regular intercourse for one year and are younger than 35 years or six months and 35 or older, then you have tried. Regular intercourse means two to three times a week. If you had intercourse with reasonable frequency for 6months to a year and you are not pregnant consult with a fertility specialist. There is a strong relationship between the length of trying and pregnancy rate. The longer that you have been trying, the lower the chance for spontaneous conception.

I did not time my ovulation

Timing your ovulation is not required at all if you are trying to conceive. Actually timing your ovulation maybe harmful to your chance to conceive. Because the methods you would use to time ovulation (cervical mucus, ovulation prediction kits, basal body temperature or intelligent thermometers and apps) are not accurate, you may miss valuable time and have intercourse at the wrong time if ovulation takes place unexpectedly early. Moreover, you cannot get higher odds for getting pregnant above and beyond  having intercourse three times a week because sperm will be available all the time when you ovulate. Several studies failed to show any increase in pregnancy rates using many of these timing methods.

On Fertility Apps and other monitors

Many (>4 million) websites discuss times intercourse utilizing other methods (fertility monitor, cervical mucus, calendar methods, urine LH kits..). More recently technology entrepreneurs are delved into the “trying to conceive” area and volunteered advice. There is no evidence to support that any calculation method improves the odds of getting pregnant over frequent intercourse. These non-scientific advice is a major distraction. Even if these apps collected data on how many women got pregnant, without a comparison group, is not a prove that they actually work. One study indicated that timed intercourse is associated with higher incidence of erectile dysfunction (43%) and extramarital sex (11%).

My progesterone level is not optimal

For almost all women, low progesterone level is not a cause for infertility. In natural cycles, progesterone starts to rise after ovulation. Levels of 3 nanogram/mL or more indicates ovulation, Optimal levels to maintain the lining of the uterus are 8 to 10ng/mL. Levels less than 8 (luteal phase defect) may lead to miscarriage because progesterone is not adequate to maintain the lining of the uterus but it is not a cause for not getting pregnant (infertility). Progesterone is monitored, and supplemented if low, during fertility treatment but in itself low progesterone is not a cause for infertility.

On Clomid & Letrozole

Clomiphene is widely used as initial fertility treatment. This use is commonly not appropriate because

a. clomid is used without infertility workup (checking ovarian reserve, sperm analysis and fallopian tubes)

b. clomid  is used without performing basic tests related to the safety of getting pregnant (infectious disease and genetic screening)

c. clomid is used by women that are not likely to benefit from it e.g regularly ovulating women with low ovarian reserve and unexplained infertility. Women that are most likely to benefit from clomid are women with chronic anovulation e.g women with polycystic ovary syndrome (PCOS).

d. clomid is commonly used with no monitoring using ultrasound. If you do not get pregnant, one would not know if you did ovulate or not. 10-20% of women do not respond to clomid. If you are destined to get pregnant, there is a possibility that you have many eggs developing in the ovary because you are unduly sensitive to the medicine. Strong response to clomid makes you at risk for multiple pregnancy

e. clomid is commonly use for extended periods of time while the majority of pregnancies take place in the first 3 months.

f. IUI is preferred to intercourse only, in clomid cycles because it can cause the cervical mucus to be thick. IUI bypasses the cervical mucus and deposit the sperm into the cavity of the uterus

g. Letrozole is similar to clomid regarding the use and indication but there is evidence that pregnancy is higher after letrozole compared to clomid.

Use clomid or better ltrozole for the right indication, with monitoring and for 3 (max 6) months only.

On Setting Time Limits

For each fertility treatment step: intercourse, ovarian stimulation + IUI or IVF define the number of cycles you will try before proceeding to the next step. Statistically, these treatments are more likely to succeed in the first three treatment attempts. Subsequently, the chance for getting pregnant diminishes and you and your physician should consider moving to another treatment.

Do not loose track of your age and ovarian reserve

You have normal fallopian tubes and partner sperm and you ovulate every month. Younger women are encouraged to try (have regular intercourse). The duration of trying on your own should be guided by ovarian reserve tests and age. Younger women with good reserve can try a bit longer than older women or women with low reserve. This recommendation should be based on scientific information not general perception. Do not accept the advice ‘ keep trying’ from any one without considering you age and without performing the tests for ovarian reserve (vaginal ultrasound, AMH and FSH on day 3). Female age is the most important factor in occurrence of a healthy pregnancy and should be the prime consideration even if ovarian reserve tests and other factors are normal.

There is a plethora of low quality information, recommendation and advice out there. Women accumulate them from multiple sources or just using there simple logic. They can lead to delay in fertility testing and fertility treatment that could be detrimental to future fertility.

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Fertility Treatments You Should Avoid

Fertility Treatments You Should Avoid

Which Fertility Treatments You Should Avoid?

Infertility is defined as inability to conceive after one year (6 months in women >35 years) of regular unprotected intercourse (no contraception) and in the absence of any known cause for infertility. Earlier referral is recommended in

  1. older women 35 years or more,
  2. unable to have intercourse (e.g erectile dysfunction..),
  3. genetic (e.g cystic fibrosis carrier), medical or pregnancy related risk factor (e.g systemic lupus, hepatitis C, HIV, hepatitis B… ),
  4. if a fertility factor is suspected (no ovulation,PCOS, hypothalamic amenorrhea, male factor, endometriosis, tubal disease..) or
  5. if fertility preservation is desired following cancer diagnosis.

Evidence is accumulating of the most effective fertility treatments after fertility assessment. Many fertility treatments are offered indiscriminately, they have little chance of succeeding or are risky (ovarian hyperstimulation syndrome, multiple pregnancy). In general simple logic does not determine if a treatment is effective or not. It is only through well conducted studies we can prove the efficacy of such a treatment. Moreover, considering the final outcome- a live healthy newborn- should be the one to look for in such a study.

The following is not a medical advice, but a review of recent evidence related to fertility treatment options. You should discuss treatment with your fertility specialist. It is possible that sometimes these treatments are indicated for fertility treatment in special circumstances. Fertility treatments you should avoid may include:

You should not time your ovulation

If you have access to intercourse with a male partner every other day, timing ovulation using any method, does not increase your chance for natural conception. If you have intercourse twice or more a week you have excellent chance of conceiving within one year. Studies evaluating timed intercourse using basal body temperature charts, urine LH kits, cervical mucus, failed to show improvement in pregnancy rate beyond intercourse every other day. No evidence that fertility apps improve the chance for conception.

Age category (years) Pregnant after 1 year (12 cycles) (%) Pregnant after 2 years (24 cycles) (%)
19–26 92 98
27–29 87 95
30–34 86 94
35–39 82 90

Use letrozole instead of clomid for ovulation induction in PCOS

There is high quality evidence that letrozole (aromatase inhibitor) is superior to clomid for induction of ovulation in women with PCOS and yeilds higher pregnancy rates. 750 infertile women with a diagnosis of PCOS, aged of 18-39 years, were enrolled: 376 patients were assigned to receive clomiphene 50 mg/day and 374 were assigned to receive letrozole 2.5 mg/day in doses escalating to 7.5 mg/day for a total of 5 days per cycle for up to five cycles. The drugs were provided in identical capsules over the same schedule. Ovulation rates with letrozole were significantly superior to clomiphene. Monthly chance for pregnancy and for a live birth was 30% higher in the letrozole group.

Avoid undergoing clomid or letrozole cycles without ultrasound monitoring

Although twins and higher order multiple pregnancies are not as common as in gonadotropin (injection medications) use [8% versus 30%] clomid is probably responsible for more twins than any other treatment because of its widespread use. Do not undergo ovulation induction without ultrasound monitoring to evaluate response and the number of follicles developing. Consider cycle cancellation if many follicles appear in the ovary.

Metformin alone is inferior to clomid in induction of ovulation and improving fertility

There is strong evidence that clomid is superior to metformin in ovulation induction in women diagnosed with PCOS. Letrozole or clomid are the medications of choice for induction of ovulation, not metformin. There is also no strong evidence that metformin reduces the chance for miscarriage.

Do not use oral medications for unexplained infertility

Unexplained (idiopathic) infertility is diagnosed in women who failed to conceive with regular ovulation, patent fallopian tubes and near normal patent sperm analysis. Women with unexplained infertility, mild male factor or minimal endometriosis do not conceive mostly because of chromosomal abnormalities of the egg. Ovarian stimulation using oral medications usually yields one or two eggs (close to natural cycles) while using injection medications can produce more eggs thus increasing the chance that one of them is healthy. There is no evidence that oral medications increase the odds of pregnancy in women with UEI.

Avoid gonadotropins-IUI and proceed directly to IVF

In women receiving oral medications (clomid)-IUI proceeding directly to IVF or proceeding immediately to IVF as first line treatment and avoiding injection medication-IUI is more successful in achieving pregnancy, is faster and minimizes the risk of multiple pregnancy.

The FASTT trial randomized 247 couples to receive three cycles of clomiphene citrate (CC)/IUI then three cycles of FSH/IUI and then up to six cycles of IVF versus 256 couples to an accelerated treatment, that omitted the three cycles of FSH/IUI. An increased rate of pregnancy was observed in the accelerated arm and pregnancy was achieved 3 months faster. Per cycle pregnancy rates for CC/IUI, FSH/IUI, and IVF were 7.6%, 9.8%, and 30.7%, respectively. The observed incremental difference was a savings of $2,624 per couple for accelerated treatment. The study demonstrated that FSH/IUI treatment was of no added value.

The FORT-T  trial randomized couples with ≥6 months of unexplained infertility with female partner aged 38-42 years to treatment with two cycles of clomiphene citrate (CC) and intrauterine insemination (IUI), follicle stimulating hormone (FSH)/IUI, or immediate IVF, followed by IVF if not pregnant. The cumulative clinical pregnancy rates per couple after the first two cycles of CC-IUI, FSH-IUI, or immediate IVF were 21.6%, 17.3%, and 49.0%, respectively. The majority (84%) of live-born infants resulting from treatment were achieved via IVF. Immediate IVF demonstrated superior pregnancy rates with fewer treatment cycles in the immediate IVF group.

Avoid using DHEA, GH or aspirin as adjuvants to IVF

There is no conclusive evidence that pretreatment, prior to IVF, with dehydroepiandrosterone (DHEA), growth hormone (GH) or other medications improves the pregnancy rate r live birth rates.

Avoid transferring two or more embryos when feasible

Multiple pregnancy carries an higher risk to the mother and to the health and neurological functions of the newborn. Outcomes in twins are definitely inferior to singleton babies. Women <38 years with a good quality embryo in there first or second IVF cycles should consider single embryo transfer. In the third cycle consider double embryo transfer.

Avoid routine use of pre-implantation genetic screening to improve the pregnancy rate after IVF

Chromosome analysis of embryos is available. There is no conclusive evidence that PGD will increase the chance for a live newborn. PGD will definitely not make the embryos healthy. If accurate, it will just enable finding the healthy embryo faster but the total number of healthy embryos, if any, will remain the same per completed IVF cycle. The accuracy of the test is no 100%, it is costly and require taking one or few cells from each embryo. Young women with good ovarian reserve have excellent pregnancy rate even with single embryo transfer. Moreover embryo freeze-thaw cycles yield comparable outcomes to fresh IVF cycles. Older women and women with low egg reserve produce a small number of embryos, which means that testing is not an efficient approach. PGD may have some role in older women e.g.>40 years producing a large number of embryos e.g >6 embryos. These women are the outliers.

Avoid using a physician with no experience in managing fertility problems

This will likely cause delay, reduce success and may increase complications. If you seek a specialist care, avoid any treatment that you do not understand its rationale. The choices are usually expectant treatment (regular intercourse), ovarian stimulation-IUI or IVF. Know the expected success rate and multiple pregnancy rate for each option offered to you by a reproductive endocrinologist.

Fertility Treatment Men Should Avoid

  1. Avoid treating abnormal sperm parameters with oral or injection medications or supplements. No such treatment was demonstrated to improve the chance for a live born in female partner.
  2. Avoid surgery for varicocele even if sperm parameters are abnormal. Surgery for varicocele is a treatment that was not proven to increase the odds of live born in female partner.

 

To lean more about fertility treatments please visit nycivf.org

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Idiopathic Infertility Treatment: what do you need to know

Idiopathic Infertility Treatment: what do you need to know

Idiopathic Infertility Treatment: what do you need to know

Idiopathic infertility (unexplained infertility) is defined as inability to conceive after trying for 6 months in women 35y or older and one year for women younger than 35, with no tubal, ovarian or male factor infertility. This diagnosis of idiopathic infertility is established after open fallopian tubes are detected in HSG or laparoscopy, regular ovulation is detected from history, lab tests and ultrasound and sperm is near normal on sperm analysis. These fertility tests can be performed within few days. Note that good health and physical fitness..etc are not factors here. Many women with terrible general health do conceive. On the other hand, many women in excellent physical fitness and sound health have extreme difficulty conceiving even with fertility treatment. Having difficulty getting pregnant without an apparent cause applies to a large category of the sub-fertile population and is puzzling to couples trying to conceive. The consensus of opinion among reproductive endocrinologist can divide the underlying factors for unexplained infertility into

1.  Chromosomal abnormalities in the egg (low egg quality)

Abnormal eggs are present in every woman, albeit to a varying degree. Older women has more abnormal eggs. In addition, the fewer eggs you have the higher the proportion of abnormal eggs. There is no non-invasive test for egg quality and history, age, blood tests for ovarian reserve and antral follicle count detected on vaginal ultrasound are the most used methods.

Factors that point to low egg quality

  1. Advanced maternal age,
  2. Diminished ovarian reserve (e.g high FSH, low AMH), also prior surgery in the ovaries, smoking, family history of early menopause and exposure to chemotherapy
  3. Early pregnancy loss before a fetal heart activity is detected (chemical pregnancy, blighted ovum),
  4. Abnormal chromosomes of the products of conception and
  5. Abnormal chromosome configuration of male or female partner e.g chromosome translocation. Less than 5% of couples miscarry due to a translocation in the male or female partner.

2. Other factors: may be more prevalent in younger patient and include mild endometriosis, immunological factors as anti-sperm antibodies, abnormality in cervical mucus, abnormalities in the cavity of the uterus and endometrial lining. Generally, these are not considered major factors in idiopathic infertility. Mostly oral medication produce few or only one follicles, thus they do not increase te chance that one or more eggs are healthy leading to a pregnancy.

Treatment Options for Idiopathic Infertility

Oral medication – IUI or expectant treatment (intercourse)

Oral medications are either clomid (clomiphen citrate) or an aromatase inhibitor (mostly letrozole) are used. This is followed by intercourse or intrauterine insemination (IUI). The pregnancy rate is about 5% to 7% per treatment cycle. There is no evidence that oral medications followed by IUI are superior to just intercourse in treatment of unexplained infertility. The risk for multiple pregnancy is about 8%. However, because oral medication (clomid) widespread use, mostly without ultrasound monitoring, they are probably responsible for more multiple pregnancy than any other fertility treatment.

Injection medications – IUI

This treatment should probably be avoided in the majority of couples because of a. No added benefit: Pregnancy rate is not significantly higher than Clomid-IUI cycles; 9% pregnancy rate per treatment cycle and drops to 5% in women >38y. b. Risks: notably multiple pregnancy (two or more babies; 30%) and higher order multiple pregnancy (three or more babies; 3 to 8%). Multiple pregnancy has significant risks to the mother and babies. Preterm delivery can be associated with permanent neurological and intellectual defects in the babies. This risk can be minimized with careful stimulation under supervision of a reproductive endocrinologist, but cannot be completely prevented.

In Vitro Fertilization (IVF)

a. The pregnancy rate per an IVF treatment cycle is approximately 30% on average,  three times that of IUI. The specific pregnancy rate is dependent on female age. The time to conception is also shorter than any other fertility treatment modality. The higher success rate can be further extended through the use of frozen embryos in couples that have good quality embryos available for freezing. The cumulative pregnancies resulting from fresh transfer and subsequent frozen-thaw embryo transfer can result in a very high odds for pregnancy. Frozen embryos can be used years after their creation, when ovarian reserve has considerably diminished. The contribution of IVF to treatment success becomes more pronounced in older women >38 years as the success of ovarian stimulation – IUI drops considerably. b. The risk for twins and higher order multiple pregnancy can be greatly minimized through single embryo transfer (1% twins and no higher order multiple pregnancy). In other words if you want to get pregnant faster, with one baby and at higher chance for success per treatment cycle strongly consider IVF with single embryo transfer.

Infertility Treatment Strategy for Idiopathic Infertility

Conventional fertility treatment: “expectant management → clomid / letrozole-  IUI x2 to 3 cycles ‍→ gonadotropin – IUI x3 cycles → IVF ” is the old method of treatment for unexplained infertility Modern treatment of Unexplained infertility: ” expectant management or oral medication – IUI → IVF preferably with single embryo transfer “. Women 38 years and older modern treatment strategy suggests Immediate IVF as the initial fertility treatment. The modern paradigm for fertility treatment will lead to pregnancy faster, is more successful, minimize multiple pregnancy and is more cost effective (lower dollar cost per baby). The majority of women (>70%) with unexplained infertility especially women with normal ovarian reserve will succeed in delivering a baby.

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Letrozole vs Clomid for Ovulation Induction in PCOS

Letrozole vs Clomid for Ovulation Induction in PCOS

Letrozole vs Clomid for Ovulation Induction in PCOS

Polycystic Ovary Syndrome (PCOS) is associated with two of the following criteria:

a. No ovulation (anovulation) or less frequent ovulation

b. Hign male hormone (androgen)

c. Polycystic appearance of the ovaries: large number of small follicles

Clomid is an oral medication that modulate or mask the estrogen receptor leading to release of internal FSH from the brain

Polycystic Ovary

Polycystic Ovary

Letrozole is an oral medicine that reduces estrogen production from the ovary through antagonizing the function of the aromatase enzyme, responsible for making estrogen. The brain respond by releasing FSH.

Which one is better?

In a recent good quality study, 750 infertile women, aged of 18-39 years, with a diagnosis of PCOS were studied. The women were randomly allocated to CC vs. letrozole for 5 treatment cycles. CC 50mg every day for 5 days (days 3-7 of cycle), or B) letrozole 2.5mg every day for 5 days (days 3-7 of cycle), for a total of 5 cycles or 25 weeks. The dose will be increased in subsequent cycles in both treatment groups for non-response or poor ovulatory response up to a maximum of 150 mg of CC a day (×5 days) or 7.5mg of letrozole a day (×5 days). 27.5% of women who received letrozole (Femara) had a live birth, compared with 19.5% of women treated with clomiphene. One quarter were clomid resistant and never ovulated.

Letrozole was associated with lower multiple pregnancy rates.

Letrozole appears to improve live birth and pregnancy rates in subfertile women with anovulatory PCOS, compared to clomiphene citrate.

Letrozole should be considered as a first line agent for induction of ovulation in women diagnosed with PCOS.

In general it is adviced that oral medication are tried first in PCOS before proceeding to injection medications (gonadotropins). Gonadotropins induce multiple ovulation and increase the risk for multiple pregnancy. If oral medications fail to induce ovulation or no pregnancy ensues, it is preferable to proceed to IVF with single embryo transfer and not injectable medications – IUI to avoid twins and higher order multiple pegnancy.

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