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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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Asian Women & Fertility Problems

Asian Women & Fertility Problems

Asian Women & Fertility Problems

Majority of Asian Women and Men agree that it is very important for them to have children. Unfortunately, many Asian couples face challenge trying to conceive naturally or using fertility treatment. The decline in natural fertility and the lower success of IUI and IVF in Asian women is documented in The US, UK, China, Japan, Korea and other Asian countries.

Fertility in Asian countries has declined to the population replacement rate 2.1 or lower. Many factors contribute to decline in natural fertility in Asian women;

Ovarian Reserve in Asian Women

When compared to Caucasian women, Asian women undergoing IVF significantly produce less eggs at all Anti-Mullerian hormone (AMH) levels, even in women with high AMH. AMH is the most accurate marker for ovarian reserve.

Gynecologic and medical disorders that impairs fertility: PCOS, endometriosis and Systemic lupus (SLE) are more common in Asian women.

Vaginismus : may interfere with regular intercourse in some Asian women.

Environmental Factors: Asian women has more exposure to methyl Mercury and vitamin D deficiency.

Culture : surveys of Asian women and men indicate that they are less likely to consent to be contacted for fertility research, are fatalistic about failure to conceive, less informed about fertility issues, only 36 percent knew that chances of getting pregnant declined with age, and are less likely to suspect a male factor.

Asian women are commonly late at seeking care for infertility and overestimate the chance for getting pregnant.

Genetics : Many genes are likely involved. FMR1 is a gene on X chromosome responsible for Fragile X syndrome and its variants. High repeats at this gene may reduce ovarian reserve.

Fertility Treatment Outcomes in Asian Couples

  1. Pregnancy and delivery rates are lower in Asian women following ovarian stimulation and IUI compared to white women
  2. IVF: when compared to white women in the US,  31 per cent of the Asian women gave birth successfully compared to 48 per cent of the white women. Asian women were also less likely to become pregnant; 43 percent against 59 per cent even after control for many fertility factors. Enodmetrial lining was thinner in Asian women compared to Caucasian women.

Asian women should be aware that fertility treatment may be less successful and seek care of a reproductive endocrinologist and fertility specialist as early as possible.

In addition there are other factors that require attention in Asian women during fertility treatment especially the higher prevalence of chronic hepatitis B infection.

After conception, asian women at are a higher risk for gestational diabetes.

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Should You Test Embryos Created after IVF for Chromosomal Abnormalities?

Should You Test Embryos Created after IVF for Chromosomal Abnormalities?

Many of the embryos created after IVF carry abnormal chromosomes. Normal embryo cells carry 46 chromosomes. The most common abnormalities are extra chromosome e. +21 (47 chromosomes) or missing a chromosome e.g -X (45 chromosomes). By far, abnormalities in the egg is the source of abnormal chromosome number.

Preimplantation genetic screening (PGS)

PGD: Testing of embryo chromosomes

Finding a ‘normal’ embryo is clearly advantages as it will theoretically lead to 1. The transfer of a single embryo instead of many  embryos and  2. can produce higher pregnancy rate than an embryo selected based on morphology (looks) alone. The process of embryo testing for the purpose of improving pregnancy rate is, however, not simple in relation to the accuracy of testing and many other issues

Preimplantation genetic screening for chromosomal abnormalites (PGS)

PGS require two steps: 1. Biopsy: obtaining a cell or a group of cells from the embryo and 2. genetic testing of the cells for chromosomes ideally in 1-2 days to obtain results and allow fresh transfer

Biopsy

Day 5 embryo biopsy

Biopsy of trohoectoderm cells of blastocyst

Obtained by removing a. a single cell of a day 3 embryo or  b. group of cells from the trophoectoderm (the outer part of the embryo that makes the placenta) of a day 5 embryo (blastocyst). Removal of cells nowadays uses a laser beam. Cells are fixed on a glass slide and sent for analysis.

Genetic Analysis of Embryos

In the past old technologies (FISH) was limited in its ability to test all chromosomes. Multiple studies in the past few years proved that PGD using FISH actually reduce the chance for pregnancy in many IVF populations and should not be used. Two newer technologies can test all the chromosomes in an embryo: cGH (comparative genomic hybridization) array and SNP (single nucleotide polymorphism) array. Some of these methods can report the results in 3 days allowing for delayed fresh transfer (day 6) and others require about a month for accurate testing, necessitating embryo freezing and transfer in frozen-thaw cycle. Labs offering these methods claim accuracy of 95 to 97%. There are more advanced methods e.g genome screening, that can test embryo chromosomes in as short as 6 hours. The ultimate method for testing is still evolving.

Should women test their embryos before transfer to the uterus?

My short answer is no, not routinely. The pros of testing embryos could be transferring less embryos , improving IVF outcomes (pregnancy rates) and avoiding pregnancy with a baby carrying chromosomal abnormalities. The cons are these aims are still not proven facts due to

1. The biopsy may hurt the embryo, reducing its ability to implant

2. The assumption that one cell represent the whole embryo may not be true (mosiacism); the cell may be abnormal while the rest of embryo is normal or vice versa

3. The methods of testing was not validated by independent large studies from multiple centers and maybe less accurate than claimed

4. Delay in transferring the embryo in the fresh cycle may reduce its implantation potential

5. Cost associated with biopsy and testing the embryo is approximately $5500 to $8000

6. Testing of an embryo will not improve the ‘pregnancy’ potential of that embryo. It will just tell you if the embryo is ‘normal’ or not. The potential from all the embryos obtained from IVF after an egg retrieval is not changed by testing. Assuming a very accurate test and an excellent freezing program,  tested embryo transfer should yield similar outcome as transferring untested embryo(s) in multiple cycles. That is the most important point to consider. If you are willing to be patient and transfer one or few embryos resulting from one ovarian stimulation successively in the fresh cycle then frozen cycles, the cumulative pregnancy and delivery rate should be the same at the end. For example in young women transferring one embryo, approximately 30- 40% of them will just achieve pregnancy in the fresh cycle. In the first frozen-thaw transfer another 30% or so will get pregnant. Frozen cycles are not as demanding as fresh IVF. Many women can have the embryo transferred in a natural cycle with no medications and minimal monitoring.

Embryo testing may help younger women, producing a large number of embryos and want to transfer only one. An alternative approach is to transfer one embryo at a time as their pregnancy rate is high even with a single untested embryo.

Testing of embryos from older women (40 or older) producing few embryos  (<6) is of little value as the alternative is to transfer 5 or so untested embryos in that age group because of the very high rate of chromosomal abnormalities in the embryos.

Testing may be helpful for older women (40 or older) producing a very large number of embryos (e.g >10 embryos) to eliminate the need for multiple transfers to get to the healthy embryo. This category (older women and very large number of eggs / embryos) is rare in IVF population.

Women contemplating testing of their embryos after IVF should consider many issues including age, number of embryos, history of unsuccessful fertility treatment if any, cost and sometimes tolerance for multiple pregnancy and fetal reduction. Moreover women should consider all these factors and be ready to modify their decision during the cycle depending on the number of available embryos.

All this does not apply to women testing the embryos for chromosome translocation, a specific genetic disease or sex.

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