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What Can you Accomplish through IVF ?

What Can you Accomplish through IVF ?

Defining your reproductive goals early on before starting  is essential in guiding the choice of treatment. IVF is the most versatile and robust fertility treatment available. In addition, it accomplish many reproductive goals that are no achievable with IUI.

What Can you Accomplish through IVF ?

Getting pregnant now

IVF can be performed in almost all causes of infertility:

Ovarian factor, male factor, tubal factor, emndometriosis, polycystic ovary syndrome (PCOS) and uterine factor. Success does not appear to be affected by the cause of infertility with the exception of diminished ovarian reserve. Hence, it is important that you seek evaluation as early as you can.

The ovary is stimulated using fertility medication. Various protocols of treatment are tweaked to your special situation and to maximize egg production. Sometimes mild or minimal stimulation IVF is a more suitable approach. Eggs are retrieved and fertilized in the lab using husband or donor sperm.

Embryos are graded based on morphology (shape) and an appropriate number is transferred into the uterine cavity. In the majority of men, sperm is obtained from the ejaculated sperm. In some surgical sperm retrieval (TESE) is required.

Getting pregnant with a single baby

Conceiving with a single baby should be the aim of every woman. The risk of twins and high order multiple pregnancy is high risk of preterm delivery. Premature delivery can lead to long term health problems in the babies. Unlike IUI where the number of embryos reaching the uterine cavity cannot be controlled, IVF allows for a strict control on the number of embryos reaching the uterus. Women with reasonable quality embryos up to age 38 or so can consider the transfer of a single embryo and freezing the other embryos.

In that regards IVF is the more conservative approach when compared to IUI, besides being several folds more successful in achieving a pregnancy.

Getting pregnant in the future with a current partner

Embryos created now after IVF, can be frozen for several years. When desired, frozen embryos are thawed and transferred into the uterus in a natural or hormone treated uterus. This allow you to extend your fertility for years to come. The survival of frozen embryos is excellent, especially using moder freezing methods (vitrification).

The pregnancy rate after transfer of frozen embryos is comparable to fresh embryos. There is also some evidence that pregnancies ensuing after transfer of thawed embryos are at lower risk for obstetrical problems.

Getting pregnant in the future with a future partner

If you do not have a male partner and do not want to use donor sperm, you can consider freezing your eggs. Because your ovarian reserve; the number and quality of eggs; will diminish as the time goes by, freezing eggs at an earlier age, enables you to freeze healthier eggs and use them years later when you are ready. Egg freezing is a fertility solution for fertile women.

Selecting the Sex of the Baby (Family Balancing)

Eggs are retrieved, fertilized. The resulting embryos are tested; one cell is obtained from each embryo and tested for the X and Y chromosomes to identify the genetic sex. The desired embryos are transferred into the uterus . Women consider sex selection for family balancing (had a baby of one sex and desire another baby of the other sex). Women consider sex selection when they want to reach their reproductive goals e.g one boy and one girl, while limiting the number of children conceived.

Getting Pregnant with Donor Eggs

For women with markedly diminished egg reserve or some genetic abnormalities, using an egg donor is an option. Egg donor may be known or anonymous. The donor is stimulated and fertilized with partner or donor sperm then the embryos are transferred to the uterus of the mother or a gestational carrier.

Becoming a Biological Parent without Getting Pregnant

Some women are not able to get pregnant in their own uteri because of a condition affecting the uterus: scarring, multiple fibroids, adenomyosis, recurrent preterm delivery..Others prefer not to get pregnant because of a general health problem: successful treatment of breast cancer, severe hypertension or heart disease. Embryos are created through IVF and transferred to the uterus of a gestational carrier (surrogate mother).

Genetically Test the embryos before getting pregnant

Embryos created after IVF can be tested genetically for i. A specific gene or ii all the chromosmes. This is accomplished through two steps. Biopsy of the embryos (one cell in day 3 embryos or few cells from the trophoectoderm of day 5 embryos – blastocysts). The cells are tested for the desired genetic target and the healthy embryos are transferred to the uterus.

Becoming a Biological Father if you are in a Same Sex Relationship

Men in a same sex relationship can father children using an egg donor and a gestational carrier. The donor ovaries are stimulated. Eggs are retrieved and fertilized  with one partner sperm or split between partners. Embryos are then transferred into the uterus of a gestational carrier.

Preserve your Fertility in the face of a medical Problem

Sometimes a a medical problem or its treatment reduces the chance for future reproduction. Breast cancer treatment in young women commonly involve treatment with chemotherapy. Medical problems other than cancer also may require treatment with chemotherapy e.g systemic lupus. Chemotherapy leads to loss of ovarian follicles and diminish egg reserve.

The ovaries are stimulated prior to exposure to chemotherapy. Oocytes are retrieved and frozen unfertilized or after fertilization. After treatment, eggs or embryos can be thawed and used for reproduction.

How Successful is IVF ?

Irrespective of the situation, the most important factor in IVF success is the number and quality of eggs remaining in the ovary (Ovarian reserve). Maternal age is the most important determinant of egg reserve. Younger women have more chromosomally normal eggs and are more likely to have a baby after IVF.

In women younger than 35, the transfer of two embryos yields a pregnancy rate of 48 to 50% and one embryo 35 to 40%. In women 40 or older the pregnancy rate per cycle is approximately 5 to 20%  depending on age. Many cycles in older women are not completed due to low response to fertility medications.

Modern IVF enables many women and men to achieve there reproductive goals and conform to their social and personal preferences and aspirations.

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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 if You had Recurrent Miscarriage?

Should you Test Embryos created after IVF if You had Recurrent Miscarriage?

PGD Recurrent Miscarriage

1. Early pregnancy loss approximately < 10 weeks, mainly due to chromosomal abnormalities of the embryo and

2. Late pregnancy loss ≥ 10 weeks due to structural uterine abnormalities, hormonal factors, blood clotting abnormalities, immunological factors and chromosomal abnormalities of the embryos (less likely than early loss).

Women with history of recurrent miscarriages should be tested for all these factors before a fertility treatment plan is finalized.

Factors that point to chromosomal abnormalities as a cause for recurrent miscarriage

  1. Advanced maternal age,
  2. Diminished ovarian reserve (e.g high FSH, low AMH),
  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.

Structural abnormalities of the uterus are detected using saline sonography, hysteroscopy or MRI scan. Blood tests can detect hormonal abnormalities, clotting abnormalities and immunological factors.

Should you Test Embryos created after IVF if You had Recurrent Miscarriage? (if chromosomal abnormalities of the embryos are suspected)

Factors to consider before deciding to test embryos:

  1. Embryos should probably be tested in women or men that carry abnormal chromosome configuration e.g. translocation as they produce higher proportion of abnormal embryos than parents of the same age
  2. Embryos should be tested if avoiding another miscarriage  is a priority, especially if prior miscarriages took place later in the first trimester and required surgery. Repeated scrapping of the uterus can damage the lining that may be difficult to treat (Asherman syndrome).
  3. There is no prove that PGD for chromosomes will improve the chance for conceiving a normal child. PGD will only detect what you have and is not a therapeutic procedure. The decision for embryo testing using PGD should be individualized for all other parents. Older women may not have any normal embryos to transfer after testing. Although testing may avoid a pregnancy with an abnormal embryo that implant and survive >10 weeks, the majority of abnormal embryos do not implant or are miscarried extremely early.

Just because it is available, sounds plausible and you have the means to do it, does not mean you should test your embryos prior to IVF.

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Sex Selection

Sex Selection

Sex selection is considered for one of three reasons:

1. Avoiding sex related genetic disorders. These are genes mostly carried on the X chromosomes and affect boys more than girls since they have one X chromosome e.g hemophilia

2. Family balancing: couples that have children of one sex and desire a child of the opposite sex

1941-2011 Trend: Suppose you could only have one child. Would you prefer that it be a boy or a girl?

Gender Selection, Boy or a Girl

3. Preference: some prefer a child of certain sex due to social factors. Recent poll in The UK  indicates that when 2,129 recently married couples were surveyed, found that 47% admitted that they would prefer to have a son first, with the majority citing practical reasons like boys being “less hard work”. Only 21% of respondents said they would like to have a daughter as their firstborn, and 32% reported having no preference either way. Couples who wanted to have a daughter first see older girls as ‘better role models’ to their younger siblings. In the US a Gallup poll yielded similar answers by American parents, especially men, since 1940s. American women do not have a proportionate preference for girls. American women show essentially no preference either way: 31% say they would prefer a boy and 33% would prefer a girl. More recent trends indicates that American couples prefer girls.

In contrast couples on a waiting list for adoption prefer girls both in the US and India. There is also some evidence that sexual orientation may influence that preference. Gay men are more likely to have a gender preference for their adopted child whereas heterosexual men are the least likely. Couples in heterosexual relationships are more likely to prefer girls than people in same-gender relationships.

The preference is also influenced by geography and politics. The official family planning policy in China, applied to large portions of Chinese, allow only for one child and does not allow sex selection. In the US many couples desire to limit the number of children to 2. If the first child is of one sex they desire the second child to be of the opposite sex

 

How is the sex of the embryo determined?

Older methods of selecting sex through change in the position or timing of intercourse or sperm sorting are not accurate and are not suitable for sex selection in modern couples seeking a specific sex (the other sex maybe conceived in 30% or more of couples). Modern sex selection depends on genetics. After stimulation of the ovaries, egg retrieval and fertilization, one or few cells from the embryo is obtained. The cells are analysed for each embryo for the X and Y chromosome. Results are obtained and are accurate >99% of the time.

After identification of the X and Y chromosomes, the desired embryo is transferred into the uterus. The embryo that carries the correct chromosome, should survive and be of good quality. Sex selection is more likely to succeed in women with good ovarian reserve, producing a good number of eggs. The larger the number of embryos available for testing, the more likely a healthy embryo of the desired sex is available for transfer.

Learn more about gender selection.

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Preconception Checklist

Preconception Checklist

What should you do if you decided to get pregnant?

Start prenatal vitamins : one tablet per day. Make sure that It contains 1mg of folic acid and has  5000 units (not more) of vitamin A

Visit your  gynecologist : for  history, exam, pap test and vaccination history.

Preconception labs : to assess the safety of pregnancy. Tests should include hepatitis B surface antigen, hepatitis C antibody, HIV, blood type, blood count, prolactin, TSH (thyroid function), cultures for gonorrhea and Chlamydia.

Genetic screening : to assess the carrier state of the parents for common genetic diseases and the risk for transmission to children. Basic tests include common mutation for cystic fibrosis, spinal muscular atrophy and fragile X syndrome. Additional tests are related to ethnicity: hemoglobin abnormalities in blacks, Mediterraneans and Asians, Ashkenazi profile for European Jews, Tay Sach disease for Jews and French Canadians. Another approach is to apply a ‘universal genetic test’ that encompasses a large number of genetic mutations for many diseases irrespective of ethnicity to allow for detection of rarer genetic diseases or even to sequence the whole genes related to theses diseases.

Lifestyle factors : better nutrition e.g one serving of small fish per week , stop smoking, avoid alcohol and reduce exercise if doing strenuous training

Worried? have a risk factor? or wants a more proactive approach?: Obtain a sperm analysis, HSG to test if the tubes are open and ovarian reserve tests to investigate the function of the ovaries (vaginal ultrasound and blood work).

Intercourse: have regular intercourse three times a week without attempting to monitor or to time ovulation.

For How Long should you try to conceive before moving to the next step?

a. If a  fertility factor known or detected e.g abnormal sperm analysis, blocked fallopian tube, no ovulation, low ovarian reserve, carrier of genetic mutation… you should seek consultation with a reproductive endocrinologist

b. If no fertility factor is known:

1. Female age < 35 years try to conceive for one year before seeking consultation with a reproductive endocrinologist

2. Female age ≥ 35 years seek consultation within 6 months if not pregnant

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Sperm Analysis in Natural and Assisted Conception

Sperm analysis is the initial test for evaluation of male fertility. Components of  sperm analysis include volume, count (concentration), movement and shape of sperm cells.

Normal Sperm Analysis

Sperm volume: the total amount of fluid produced. Commonly 1.5 mL or more.

Sperm count: number of sperm in each mL of fluid. Normal concentration is 15 to 20million per mL. Total count= volume x concentration (count).

Sperm motility: % of sperm with vigorous or moderate movement. Total motile sperm count=volume x concentration x %motility

Sperm morphology: Shape of sperm using strict (Tygerberg, Kruger) criteria 4% normal or more

Strict Sperm Morphology

Strict Sperm Morphology

Lower reference limits for men whose partner conceived within 12 months after stopping use of contraception had the following parameters (WHO manual , 5th ed.) are:
Semen volume (ml) 1.5 (1.4–1.7)
Total sperm number (106 per ejaculate) 39 (33–46)
Sperm concentration (106 per ml) 15 (12–16)
Total motility (PR + NP, %) 40 (38–42)
Progressive motility (PR, %) 32 (31–34)
Vitality (live spermatozoa, %) 58 (55–63)
Sperm morphology (normal forms, %) 4 (3.0–4.0)

All parameters should be interpreted in conjunction with clinical information. If abnormal it can be repeated in 2 to 3 months.

How much sperm is enough?

Evaluation of male fertility through sperm analysis is complex. Clinical factors in history and examination should be considered. Total sperm count in the specimen is an important factor e.g low sperm morphology in specimen of 200 million sperm may have a different effect than low morphology in a specimen of 30 million sperm. Although there are notable variations in a sperm sample of the same man over time, there is no evidence that repeat evaluation of semen in helpful in managing infertility in a female partner.

Since we have very limited tools (medications, supplements, surgery) to meaningfully improve sperm parameters and fertility, a practical management of fertility due to male factor is:

>10 million motile sperm: suitable for natural conception and IUI

2-10 million motile sperm: suitable for IVF

<2million motile sperm or strict morphology <2% suitable for IVF with ICSI (intracytoplasmic sperm injection)

IVF + ICSI is indicated if surgical sperm harvest is needed and some cases or retrograde ejaculation and anti-sperm antibodies.

Can the sperm analysis be improved?

The count, motility and morphology can sometimes be improved (lifestyle modifications, medicine, surgery). Two important tips to consider though

a. In the majority of cases, there is no evidence that this improvement increases the odds of a pregnancy in female partner

b. The delay in treatment is sometimes critical for women with low egg reserve while they wait for their partners to improve there sperm parameters

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Frozen Embryo Transfers (FET)

Frozen Embryo Transfer

Following IVF, excess embryos are frozen for use with second attempts if no pregnancy takes place or to conceive a second child. With improvement of the freezing and thaw techniques: the majority of frozen embryos survive thawing, the implantation potential of a thawed embryo is comparable to a fresh embryo, less embryos or single embryo can be transferred in the fresh cycle and selection of the best embryo for fresh transfer became less important.

Frozen embryo transfer: blastocysts and cleavage embryos can be vitrified after IVF

Frozen embryo transfer (FET)

Freezing of embryos allow ample time for genetic testing of embryos if needed, transferring embryos to a different locale, delaying transfer due to medical problem, the emergence of an abnormality in the lining of the uterus e.g thin  endometrium, polyp, fluid.. or till a gestational carrier is found.

Benefits of Frozen Embryo Transfer

1. Pregnancy rate after frozen embryo transfer is comparable to fresh transfer and may even be higher than fresh transfer in some studies. More work is needed to confirm higher live birth rate.

2. Complications: frozen embryo transfer minimize some of the complications related to IVF. Ovarian hyperstimulation syndrome (OHSS) and possibly ectopic pregnancy (pregnancy in the fallopian tube)

3. Lower risk for pregnancy complications and better quality baby: frozen transfer appear to reduce the risk for preterm delivery, bleeding in pregnancy and low birth weight, possibly due to better placental function.

How is the lining of the uterus prepared for frozen embryo transfer?

1. Natural cycle: in ovulating women, the follicle in the ovary is monitored till the point of ovulation is accurately identified. The follicle will internally produce the estrogen required to build the lining. When ovulation takes place, the embryos are thawed and transferred in a day comparable to its age e.g a day 5 embryo is transferred 5 days after ovulation. This process require only ultrasound and blood work monitoring

2. Estrogen replacement cycle: ovulation is stopped and estrogen is supplemented externally (patches,oral or vaginal) till the desired thickness and pattern of the uterine lining. Progesterone is then started (injection or vaginal) then embryos are transferred.

Timing of thaw and transfer is a complicated question and it depends on the type of cycle and age of embryos. Sometimes embryos are thawed and cultured for few days before transfer

All method for endometrium preparation yield similar pregnancy rate. At NYCIVF we prefer natural cycle with luteal phase support using vaginal estrogen.

What makes a frozen embryo transfer cycle successful?

Embryo quality: one or more top quality embryo morphology observed at any stage of culture improves the outcome even if high-quality characteristics disappeared before transfer. Transferring more than one embryo increases the pregnancy rate but also multiple pregnancy.

Conclusion: should you intentionally delay transfer to frozen cycle? no but if you need to freeze the embryos, expect similar pregnancy rate as in the fresh cycle.

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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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Fertility in Men Diagnosed with Cancer

Fertility in Men Diagnosed with Cancer

Who needs to consider preservation of Fertility?

a. The American Cancer Society estimates that 760,000 men will be diagnosed with cancer in 2009. Cancer itself (before treatment) is sometimes associated with less sperm production in men. This is specially the case in Hodgkin’s lymphoma, testicular cancer, prostate cancer, leukemias and colon cancer. The most harmful factor, however, is cancer treatment. Chemotherapy and radiation significantly impair sperm production. The effect of chemotherapy depends on age, drug used, dose and duration. Cyclophosphamide appears to be the most harmful agent. Radiation also impairs sperm production especially at doses of 1200cGy or more.

Sperm count sometimes recover to a variable extent years after cancer treatment. This depends on the type of cancer and treatment used. For example 90% of men diagnosed with Hodgkin’s lymphoma, treated with MOPP chemotherapy regimen, do not have any sperm in the ejaculate after one year.

b. Bone marrow transplantation for cancer of nonmalignant diseases usually require prior irradiation and chemotherapy. This is associated with high risk (85%) of complete failure of sperm production.

c. Connective tissue / autoimmune diseases as lupus and rheumatoid arthritis requiring treatment with chemotherapy.

d. Genetic abnormalities associated with rapid loss of male germ cells e.g. Kleinefelter syndrome, Y chromosome microdeletion (AZFc).

Methods used for Fertility Preservation

Methods used to preserve fertility in men are generally divided into two categories:

Protection of the testes from damage caused by cancer treatment:

1. Shielding the testes from radiation field.

2. Protection of the testes from the effect of chemotherapy.

GnRH agonists are a group of medications that suppress the master gland in the brain, preventing the release of the hormones that stimulate sperm production in the testes. Although suggested, there is no proof that they actually increase the odds for pregnancy after the use of chemotherapy. Actually, there is no effective protective medication available for use in men or women.

Low Temperature Storage of Sperm and Testicular Tissue:

a. Sperm Cryopreservation. This is the standard method for preservation of fertility in men. A sperm sample is obtained by masturbation and frozen for later use. If feasible multiple samples are obtained. In the future, sperm sample are used for intrauterine insemination or IVF / intracytoplasmic sperm injection (ICSI). Banking sperm was found to offer not only a chance to father children in the future but also encouragement and improved morale during disease treatment especially if it was initiated by the patient own initiative.

Lack of information and counseling is the most important reason why men diagnosed with cancer do not bank their sperm.

Although freezing may reduce the quality of sperm especially if it was not optimal before freezing, modern reproductive medicine can handle the majority of compromised specimens yielding excellent pregnancy rates, similar to those of fresh sperm.

b. Testicular Sperm Extraction (TESE). This surgical procedure retrieves sperm from inside the testes if no sperm was found in the ejaculate. If this procedure is used before cancer treatment, sperm are retrieved in over 50% of cases. Sperm or testicular biopsies are frozen for later use. ICSI is used for fertilization. In case of testicular cancer, sperm retrieval can be performed at the same time of surgery for cancer.

c. Testicular Tissue or Germ Cell Freezing. This is an experimental technique. Immature germ cells or testicular pieces are frozen for later transplantation. No pregnancy was achieved using this method so far.

In conclusion, fertility-sparing strategy is readily available to the majority of men at risk for diminished fertility through sperm cryopreservation. Men interested in fathering children in the future should be counseled about this option.

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Fertility in Women Carrying BRCA Gene Abnormality

Fertility in Women Carrying BRCA Gene Abnormality

Fertility in women carrying BRCA gene abnormality may be reduced

Women carrying BRCA gene abnormality frequently consult with reproductive endocrinologists for fertility treatment or preservation.  Women referred to test the BRCA gene for mutations based on ancestry, family history and type of cancer diagnosed in her family. If a mutation is found the lifetime risk for breast cancer is 70% and ovary cancer is 40%.

Fertility in women with BRCA mutations maybe reduced in reproductive age women because of the mutation itself, procedures used to reduce the risk of cancer or cancer treatment if they develop cancer.

 

BRCA mutation and Fertility

BRCA mutation and Fertility

Ovarian Reserve and Response to Ovarian Stimulation

Women carrying a BRCA mutation may require ovarian stimulation using fertility medications for

  1. Preservation of fertility through egg freezing or embryo freezing prior to prophylactic removal of both ovaries,
  2. Preservation of fertility after the diagnosis of breast cancer and before chemotherapy or
  3. An incidental fertility problem unrelated to BRCA mutation.

Ovarian reserve and response to fertility medication is one of the most determinants of success of fertility treatment or preservation.

Although it was suggested that women with BRCA mutations respond more modestly to fertility medications, this was not proven. When women carrying these mutations were compared to relatives with no mutations, there were no differences in the number of deliveries and the need for fertility treatment. Also in a study of 260 Ashkenazi Jewish women with ovarian cancer and 331 controls, unselected for age or family history of the disease. Pregnancy success was similar for 96 mutation carrier and 164 non-carrier cases and controls.

Fertility & fertility treatment

Its unlikely that fertility or fertility treatment will increase the risk for breast cancer in women with BRCA mutations. 1380 women diagnosed with breast cancer and carrying BRCA mutations were matched 1380 women without breast cancer and carrying BRCA mutations. 16% reported fertility problems, 4% used fertility medications and 1% used IVF. There was no difference between women who developed breast cancer and those who did not regarding history of infertility and the use of fertility medication. The type of fertility medicine-oral or injection medication also did not change the risk for breast cancer, irrespective if women had children before or not.

Interestingly, there is significant excess of females among the offspring of female carriers of BRCA1 and BRCA2 mutations-higher female to male ratio.

Avoiding BRCA transmission to babies (PGD)

Women interested in getting pregnant should be counseled to the risk of transmission of mutation to future children. Both men and women carrying the mutation are at a significantly increased risk of cancer. It is very possible to prevent this transmission if the eggs or embryos are tested before replacement into the uterus in women undergoing in vitro fertilization – IVF Eggs are tested by polar body biopsy (this is a small cell attached to the egg and carry chromosomes representative to those of the egg). Embryos are tested by testing one cell of a 6 to 8 cell embryo. Testing has many medical and ethical dimensions and is better handled by providers specializing in these areas.

Pregnancy

The risk of breast cancer may increase with multiple pregnancies and deliveries in women carrying BRCA2 mutations. In BRCA1 mutation carriers, late menarche and breast feeding reduces the risk for breast cancer. The effect of pregnancy on cancer risk though was not confirmed in multiple studies.

Read more to learn about different methods for preserving fertility after BRCA diagnosis.

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