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Should you Consider Fertility Assessment when you do not Intend to Get Pregnant Soon?

Should you Consider Fertility Assessment when you do not Intend to Get Pregnant Soon?

If you do not intend to become pregnant in the near future, do you need to assess your fertility? It is very possible that many women and men will be screened for relatively a small number of individuals that will show abnormalities. From the individual point of view, however, there are two distinct potential benefits:

Detection of abnormalities related to fertility and reproduction:

consider fertility screening if you intend to delay pregnancy or knon fertility issue

Screening for fertility problems

Ovary: Diminished ovarian reserve and anovulation

Fallopian Tubes: tubal block

Male factor: abnormal sperm analysis

Other factors: abnormalities of the uterus or cervix

Detection of abnormalities related to the safety of getting pregnant:

Screening for genetic abnormalities: carrier screening

Screening for other medical disorders and infectious diseases

The decision to consult with a reproductive endocrinologist to assess your fertility is individual. One would be more interested in fertility consultation in the presence of

1.  Known Fertility Issue: PCOS, absence of menses, endometriosis, fibroids, PID, abdominal surgery, prior chemotherapy for cancer or lupus

2. Risk factor for low fertility: 35 years or older and intend to delay pregnancy

3. Genetic or medical risk factor: genetic screening especially in certain ethnic groups e.g Ashkenazi Jewish individuals

Informed about your fertility potential you may elect to either do nothing or respond to the abnormal results. If diagnosed with lower ovarian reserve you may elect to attempt pregnancy sooner or freeze your eggs. If a genetic abnormality is found in both partners you may consider testing of embryos to avoid transmission to the babies. If an abnormal sperm parameters were found, a referral to a urologist and / or sperm freezing could be considered.

There are no clear cut recommendation for fertility screening in men and women not intending pregnancy in the near future. Women intending to delay getting pregnant or with a known fertility issue and certain ethnic groups should consider screening for fertility and genetic problems.

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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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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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What do Millennial women think about infertility?

What do Millennial women think about infertility?

What do Millennial women think about infertility?

Millennial generation were borne between 1982 and 2000. They have commonalities not shared by other generations. Generation Y is the highest-educated generation in American history.

On the Incidence of infertility in the US

The 2006–2010 National Survey of Family Growth (NSFG), indicates that the incidence of infertility among married women aged 15–44 is 6.0% (1.5 million) in 2006–2010, down from 8.5% in 1982 (2.4 Million women).
Impaired Fecundity (ability to have a live birth) among married women aged 15–44 Increased from 11% In 1982 To 15% In 2002, But decreased to 12% In 2006–2010. Both Infertility and impaired fecundity remain closely associated with age. The decline is probably reflects greater delay in childbearing (less women attempt to conceive thus less fit the definition of infertility).

Infertility prevalence can be estimated using two approaches: [1] a constructed measure derived from questions on sexual activity, contraception, relationship status, and pregnancy, and [2] a measure based on estimated time to pregnancy derived from the respondents’ current duration of pregnancy attempt (i.e., current duration approach). Prevalence was approximately twofold higher using the current duration approach (15.5%) vs. the constructed measure (7.0%). Both methods identified similar patterns of effect of increasing age (American Society for Reproductive Medicine 2013).

On Delaying Marriage in Generation Y

According to Pew Research Center analysis of U.S. Census data, 51% of US adults are currently married. Only 22% of Millennial women are married. The median age of first marriage for Gen Y women is 26.5 years and for men 28.7. Currently, there are more unmarried women in their early 30s than at any time in the last 60 years in the US.

What do Millennial women think about infertility? Generation Y : late marriage and late first birth

Millennial Women : late marriage and late first birth

Millenials give birth to their first child  many years later than predecessors. The mean age at first child’s birth for women was 23 and the mean age at first child’s birth for men was 25 and even much later in more recent research (The Guttmacher Institute). One-half of first births to women were in their 20s and two-thirds of first births were fathered by men who were in their 20s. On average, women aged 15-44 have 1.3 children as of the time of the interview.

Delay in bearing a child remains true even after cohabitation and other adult living arrangements are considered. The gap between first sex and first birth is 9+ years for Gen Y and 3+ years for Gen X.

 

Millennial Women Overestimate their Fertility Potential

Many Generation Y women, age 25 to 35, think a 30 year old woman has a 70-per cent chance of conceiving per month and in a 40 year old is close to 60% (Fertility IQ 2011 Survey, 1,000 women). Women were wrong most often about how long it takes to get pregnant and about how much fertility declines at various ages.
It is not clear why do millennials overestimate their fertility potenials possible explanations could be [1] Ignoring the disconnect between general health and ovarian aging; women can be very healthy and have very few eggs remaining in the ovary.
[2] Media celebrated older high profile and celebrity births in mid 40s.
[3] Some success of fertility treatment in older mothers.

Generation Y women are anxious about their fertility

Perceived infertility is the individual’s belief that she or he is unable to conceive or impregnate, regardless of whether this belief is medically accurate. Overall, 19% of women believed that they were very likely to be infertile, according to a Gutmacher institute 2012 survey of 1,800 unmarried men and women aged 18–29. A survey from Europe indicates that 31% of women and 52% of men believe that dramatic decline of fertility occurs after age 44.

 On The Utilization of Fertility Services by Millennial Women

Millennial women appear to utilize Fertility Service different than generation X. Twelve percent of women aged 15-44 in 2006-2010 (7.3 million women), or their husbands or partners, had ever used infertility services. Among women aged 25-44, 17% (6.9 million) had ever used any infertility service, a significant decrease from 20% in 1995. Thirty-eight percent of nulliparous women with current fertility problems in 2006-2010 had ever used infertility services, significantly less than 56% of such women in 1982. In all survey years, ever-use of medical help to get pregnant was highest among older and nulliparous women (NSFG). Gen Y also overestimate the success rate of IVF.

Consideration of fertility by generation Y without changing reproductive plans include

  1. No harm in evaluation of ovarian reserve. Some women, though very young, do have a diminished ovarian reserve to the extent that delay of seeking fertility treatment is detrimental to there ability to conceiving a biological child
  2. Delaying childbearing does not mean ignoring fertility for an undefined period. Many options can be exercised to preserve fertility, including lifestyle modifications, egg freezing and embryo freezing.
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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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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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IUI or IVF for Unexplained Infertility

IUI or IVF for Unexplained Infertility

Choosing IUI or IVF for unexplained infertility can be confusing. If you have been trying to conceive for several years and initial fertility tests does not reveal any abnormalities (open fallopian tubes, normal sperm and regular ovulation), you will be diagnosed with unexplained or idiopathic infertility.

Possible treatments include ovarian stimulation-IUI or IVF

What should you consider before deciding between IUI and IVF?

IVF In Vitro Fertilization

IVF In Vitro Fertilization

 

Intrauterine Insemination (IUI)

Intrauterine Insemination (IUI)

  1. Pregnancy rate: IVF is associated with higher pregnancy rate than IUI, approximately 3 times. In women less than 35 pregnancy rate is approximately 50% with 2 embryo transfer and 35% with one embryo transfer versus 10-15% per one cycle of IUI.
  2. Multiple pregnancies: When ovulation is stimulated using injection medications (FSH) the chance for twins is about 30% and higher orders multiple pregnancies 1-3%. Multiple pregnancies is associated with increased risk of preterm delivery with possible long term effects on the newborns. Compared to IVF with single embryo transfer, the chance for twins is 1% and higher order multiples is very low. Actually IVF with single embryo transfer is the more conservative approach in women at risk for multiple pregnancies with IUI.
  3. Cost: IVF is more costly due to the requirement of lab procedures to fertilize the eggs and culture the embryos. If multiple pregnancies at it complications are factored in IVF with single embryo transfer appears to the cheaper approach.

Sound evaluation by a reproductive endocrinologist can give you the advice and guide you through the decision.

Women with high ovarian reserve as PCOS are better served in general by avoiding injection medication + IUI and proceed to IVF if oral medication e.g clomid do not succeed. Women with reduced ovarian reserve generally will have a high odds for getting pregnant with IVF than IUI.

 

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Trying to Conceive (TTC): What Does Timed Intercourse Means?

Trying to Conceive (TTC): What Does Timed Intercourse Means?

If you are trying to conceive (TTC) there is one thing you need to do as it is very helpful in achieving a pregnancy.

There are also few things that are not very helpful.

Timed Intercourse : How to do it?

The majority of pregnancies take place when intercourse takes place in the six day and especially two day period ending in the day of ovulation (fertile window). Some advice that ovulation should be timed using cervical mucus, basal body temperature or urinary luteinising hormone (LH) kit.  Several factors are against this approach:

  1. Timed intercourse is emotionally stressful
  2. Sperm survive in the cervix, uterus and fallopian tubes for several days (>3 days, close to 7 days)
  3. Studies that evaluated the use of mucus, BBT or LH kits to time intercourse did not report better odds for natural conception.

The best approach to a timed intercourse is not to time it at all provided that sex is frequent enough to maximize the chance for sperm-egg interaction. Intercourse three times a week appears to optimize the chance for natural conception.

It is not true that frequent intercourse reduces the pregnancy rate due to reduced sperm count and quality.

Timed Intercourse : How long?

Approximately 85% of women trying to conceive conceive within the first year. The American Society for Reproductive Medicine recommend seeking consultation if pregnancy does not ensue after one year of intercourse in women younger than 35 years and six months in women 35 years and older.

The limited Value of Cervical mucus, BBT and LH kits

Cerivcal mucus, BBT and LH kit are not accurate methods to time ovulation. Fluid cervical mucus, rise in temperature and positive urine LH can take place without ovulation or several days before ovulation. Studies evaluating these methods did not find and increased chance for pregnancy. Using a calender or App to register symptoms and mucus was not scientifically evaluated.

For a minority of couples that cannot have frequent sex (every 2 to 3 days) the use of LH kits maybe helpful. All the other methods (mucus, temperature) had less than 50% correlation to ovulation.

Fertility Apps

Fertility Apps

Fertility Apps

Fertility apps are generally not helpful in enhancing fertility because they are not based on scientific information. The premise that cervical mucus character, urine LH kit and BBT charts are better than frequent intercourse is not scientifically correct. Thus apps based on tracking ovulation cannot contribute to your fertility beyond intercourse three times a week. No app so far was scientifically tested and was shown to enhance fertility in women or men.

Conclusion: Do have intercourse three times per week after the end of bleeding days. Do not time intercourse. If you must use urine LH kit. If you do not conceive in 6 months (≥35y) or a year (<35y) consult with a reproductive endocrinologist. Throw your iphone or keep it and delete the app (till a truly helpful app is available).

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Endometriosis & Infertility

Endometriosis & Infertility

Endometriosis & infertility commonly coexist. Endometriosis can have profound effects on woman’s fertility and the ability to conceive in the future, either by virtue of the disease itself or its treatment. Endometriosis means that the tissue that lines the uterus is found in other areas, most notably the ovaries and the lining of the pelvis, frequently causing pelvic pain and infertility. In early stages of endometriosis, the implants in the pelvis may chemically affect various stages of reproduction including fertilization and implantation. In later stages, endometriosis incites scarring that can block the fallopian tubes and can produce cysts in the ovaries called endomertiomas. Experienced reproductive endocrinologist can diagnose endometriomas with high degree of accuracy using ultrasound. In other areas the diagnosis of endometriosis may requires laparoscopy.

Treatment of Endometriosis

Women seek treatment for endometriosis because of pain or infertility. Treatment for endometriosis is either medical or surgical.

Medical treatment For Endometriosis

It entails suppression of ovulation and estrogen production. Estrogen stimulates the growth of endometriosis. Medical treatment has side effects and is not suitable for women seeking pregnancy now. It, however, does not have a long lasting effects on fertility. Medications used include oral contraceptive pills, androgenic medications or gonadotropin releasing hormone agonists as depot leuprolide. Women on these medications does not need to consider fertility preservation strategies because of treatment.

Surgical Treatment For Endometriosis

Surgery aims at removal of endometriosis spots in the pelvis or excising endometrioma cysts from the ovary. Cutting the ovary and stripping the wall of the endometriomas is associated with loss of eggs during the procedure. The ovary, where the procedure is done commonly have less reserve and may show lower response to fertility medication. The risk for decreased fertility is higher if the procedure is done on both ovaries. It is also higher after extensive surgery, commonly associated severe disease in the pelvis. Sometimes the ovary need to be completely removed . Removal of endometriosis deposits in the pelvis-usually burning them using cautery-can also incite scarring that can block the fallopian tubes. Women undergoing surgery for endometriosis should consider fertility preservation. Aspiration of endometriomas is generally not a recommended treatment as they tend to recur and can cause infection.

Fertility Treatment in Women with Endometriosis

Severe Endometriosis mechanically blocks the fallopian tubs due to scarring. IVF appears to be the best treatment option. Although endometriosis reduces the response to ovarian stimulation, it does not appear to reduce the pregnancy rates

Mild endometriosis does not distort the fallopian tubes. Two treatment options are available: laparoscopy with excision or burning of endometriosis or ovarian stimulation + IUI. Both can increase the chance for pregnancy but IUI is less invasive.

Fertility Preservation strategies in women with endometriosis

Reproductive age women diagnosed with endometriosis and advised to undergo surgery by their physicians should inquire about the possible effects of surgery on future fertility and consider fertility preservation strategies. Strategies include embryo cryopreservation, egg freezing or ovarian tissue freezing.

Embryo cryopreservation

Its the standard method for preservation of fertility. It requires stimulation of the ovaries using fertility medication for approximately 10 to 12 days, followed by egg retrieval. Eggs are fertilized using partner or husband sperm. The resulting embryos can be frozen indefinitely. One risk is that endometrioma cysts can get infected at the time of egg retrieval.

Egg freezing

It can be used in women not in stable relationship and declining the used of donor sperm. It require ovarian stimulation. This is followed by retrieval and freezing. Eggs are frozen using vitrification. Vitrification is associated with better survival after thawing than slow freezing. When desired, the eggs are thawed and fertilized using intracytoplasmic sperm injection-ICSI and the resulting embryos are transferred to the uterus.

Endometriosis and Ovarian Cancer

It was noticed that women diagnosed with endometriosis has a small increase in the risk for certain rare types of ovarian cancer. Its essential that endometriomas in the ovary be thoroughly investigated using ultrasound and other imaging modalities and sometimes blood tests. Surgery may be needed to remove the cyst and submit it for pathological examination to exclude cancer.

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