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What if You Have Dual Infertility Factor

What if You Have Dual Infertility Factor

What if You Have Dual Infertility Factor

Many Times You Do

Infertility factors are generally classified into tubal factor (blocked fallopian tubes), male factor (abnormal sperm concentration, movement or shape) and ovarian factor (no ovulation). In the majority of situations though multiple factors exist. If you partner has low sperm count, you also may have a blocked tube. Women who do not ovulate can also have endometriosis. Some men think that their female partners are infertile due to a female factor while they also have subtle sperm abnormality that prevents fertilization. Women sometimes think their male partners sperm is abnormal while they also have low egg reserve and low egg quality. Couples potentially have a dual infertility factor, most of the time. Most notably, low egg number and quality should be considered in any couple seeking fertility evaluation and treatment. Even young women with good egg reserve have abnormal eggs.

Irrespective of infertility factors, consideration of other general factors e.g genetic screening results can have a significant impact on choice of fertility treatment modality. If both partners are carriers for cystic fibrosis, they may require embryo testing (PGD) in the setting of IVF as opposed tosimilar couples without this genetic risk factor.

Do not Accept Treatment Before a Complete Workup. Do not Accept Empiric Treatments

For that reason, no assumptions about fertility factors and treatment should be made before a completed workup for sperm, ovulation, ovarian reserve, Fallopian tubes and general factors (genetic and preconception screening). This careful and deliberate testing is unfortunately not always followed. In many cases, couples are treated with empiric treatments. Here are two very common empiric treatments commonly prescribed

a. Clomid used for everyone. Clomiphene is suitable as initial treatment for women who do not ovulate due to polycystic ovary syndrome (PCOS), have open tubes and normal sperm analysis. In modern reproductive medicine, clomid should not be used without testing of male and tubal factor. Clomid also should not be used in older women that ovulate regularly. The majority of these women are older and do not get pregnant because of lower egg quality. They require superovulation (more than one eggs) to compensate for lower egg quality.

b. Progesterone supplementation. Low progesterone can cause early miscarriage (not infertility) in a small percentage of women. Women that yield low progesterone after ovulation do so because of abnormal development of follicles. They are better served by induction of ovulation to produce better follicles, rather than progesterone supplementation. During fertility treatment, progesterone levels are monitored and maybe supplemented if low. Progesterone treatment in itself is not a treatment for any form of infertility.

c. Laparoscopic surgery for endometriosis. The magnitude of benefit for surgical treatment of infertility associated with endometriosis is limited and maybe harmful. Laparoscopic surgery for severe endometriosis is risky e.g bowel injury. Resection of endometrioma can reduce ovarian reserve. IVF is a better than laparoscopic surgery in treating infertility due to moderate and severe endometriosis . The increase in pregnancy rate after excision of mild endometriosis is limited (probably 30 surgeries are needed to produce one newborn).

d. Varicocele repair for male factor infertility. Although sperm parameters may improve after varicocele repair, there is no conclusive evidence that it will translate into higher odds of pregnancy in female partners. There is a limited indication for varicocele repair aiming at improving fertility in males.

Many of these empiric treatments and prescribed with no or limited scientific basis and represent bias and expertise of the prescriber.

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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 Options

Fertility Treatment Options

Fertility Treatment Options: What Are Infertility Treatments?

 

 

Following detailed fertility investigation of the male tubal and ovarian factors, patient and her reproductive endocrinologist decide together on the optimal fertility treatment options.

Factors to consider in selecting the best fertility treatment options include:

Sperm source

  1. Is there a male partner: if so what is the ejaculate volume, sperm concentration, motility and shape? if >10 million moving sperm then pregnancy through intercourse or IUI is possible. Lower numbers indicates IVF or ICSI. If azospermia (no sperm in the ejaculate) then surgical sperm retrieval may be needed (TESE) or donor sperm can be used.
  2. If there is no male partner: anonymous or known donor sperm is used

Tubal Factor

  1. Open fallopian tubes allow for natural conception or IUI.
  2. Blocked fallopian tubes require IVF. Sometimes tubes can be fixed using tubal surgery.
  3. Blocked and dilated fallopian tubes (Hydrosalpinx) require surgical removal of the dilated tubes followed by IVF. Dilated tubes are very difficult to fix and can leak fluid into the uterine cavity and prevent implantation of the embryo.

Ovarian Factor

  1. Women who do not ovulate due to polycystic ovary syndrome  (PCOS): ovulation can be induced using oral medications (clomid or letrozole) or injection medications  (gonadotropins). This is usually combined with IUI.
  2. Women who do not ovulate due to defect in the master gland in the brain (Hypothalamic amenorrhea): ovulation can be induced using injection medications  (gonadotropins). This is usually combined with IUI.
  3. Women diminished ovarian reserve and unexplained (idiopathic) infertility commonly have lower quality eggs and may benefit from inducing multiple ovulation followed by IUI or IVF, to increase the chance that one of the eggs is healthy (chromosomally normal).

Donor Eggs

  1. Donor eggs are needed in women with low egg reserve that fail multiple IVF cycles after menopause or those who carry some genetic abnormalities.
  2. Donor eggs can enable same sex male couples parent a child (together with a gestational carrier).

Gestational carriers

  1. Gestational carriers enable women to parent a child if the uterus is absent or was removed due to a disease e.g endometrial cancer or if the lining of the uterus is damaged e.g intrauterine scarring due to prior scrapping.
  2. Gestational carrier enable women who cannot get pregnant to parent a child e.g history of breast cancer
  3. Gestational carriers enable same sex male couples to parent a child.

Genetic analysis of the eggs or embryos (PGD)

  1. Women and men with risk of conceiving a child with a specific genetic disorder e.g cystic fibrosis, sickle cell anemia should consider testing their embryos before transfer into the uterus (PGD)
  2. PGD can also be used for selecting the sex of the baby for family balancing.
  3. PGD can be used to test the chromosomes of the embryo to increase the chance for pregnancy in women select women but its efficacy for that purpose is still being investigated.

Fertility Preservation

  1. Women at risk for diminished fertility due to a medical problem or treatment e.g breast cancer can freeze their eggs or embryos to use later
  2. Men at risk for azospermia due to genetic factors, cancer and cancer treatment can freeze sperm for use later
  3. Many other techniques for fertility preservation can also be applied to adults and children to preserve reproductive organs and tissue.

 

Many fertility treatment choices exist to help women and men conceive a child. One or more of these methods can be tailored to each

i. individual circumstances:

singles women or men,

heterosexual couples or

same sex couples.

ii. reproductive aim:

wants to get pregnant now versus later,

wants one child only or accepts twins,

wants to conceive a child of certain sex,

will use own uterus or a gestational carrier,

will use own gametes- sperm or egg or donor gametes.

 

To learn more about  fertility treatment options please visit nycivf.org

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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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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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