Birds, Bees and Bunnies: The Biology of IVF – Part 3 (Sperm & Embryos)


This article discusses the basic biology behind the process of In Vitro Fertilization (IVF) and may be helpful to couples who plan to undergo IVF. Technical terms may be found in a glossary at
CNY Fertility Center has locations in Syracuse, Albany and Rochester, NY. CNY Fertility Center offers couples and individuals affordable fertility treatments including low cost IVF (In Vitro Fertilization) by our experienced and caring staff.

Sperm penetration and fusion, cortical granule reaction, from
Once one sperm has penetrated, the cortical granule reaction causes a shield to slam shut just inside the egg membrane within microseconds. This prevents the entry of another sperm. If this system fails and two sperm enter, there are two sets of male chromosomes.  This is called polyspermy and actually is observed commonly in the IVF lab. Three pronuclei, a sign that an entire extra set of chromosomes is present is a fatal flaw.

In IVF, in cases of low sperm numbers when the sperm function is inadequate for this task, delicate micromanipulation tools are brought to bear. Using methods developed by cell biologists, the embryologist sits before controls like joysticks on a video game. Imagine threading a bit of angel hair into a speck of dust and you will be able to understand how intracytoplasmic sperm injection (ICSI) is done. Now a daily part of the armamentarium of highly skilled IVF embryologists, it is nonetheless an amazing advance.

ICSI, intracytoplasmic sperm injection. From
After fertilization, in the incubator, the pronuclei can be seen on day one. On the first day after insemination, the IVF embryologist looks for the two pronuclei as an indicator that fertilization has occurred. Further scrutiny of these under high magnification gives clues as to the future.  Lynnette Scott PhD in Boston among others has developed a system of predicting outcomes based on the tiny nucleoli in the pronuclei. If they line up in an orderly manner the embryos may progress. If they are disorganized there is a good chance development will be impaired.

On day three the embryos are 5-8 cells

8 cells
Sometimes embryos are cultured to day 5 at the blastocyst stage
Assisted hatching is done to assist the hatching of the blastocyst through the zona

Normal zona

Thin zona

Laser ICSI used to breach the zona, as used for assisted hatching, from

Counting the chromosomes in the pregnancy tissue is recommended if a miscarriage occurs after IVF. This test can be performed in a genetics laboratory on miscarriage tissue in order to determine if one of these errors caused the loss. When aneuploidy is found in the tissue by chromosome testing, we are reassured that the loss was not due to a disease in the mother.
In IVF a common occurrence is the early pregnancy which attaches and produces a positive test, but then dies within a few days. Because we only know there is a pregnancy by looking at a biochemical reaction, the pregnancy test, this event is called a biochemical pregnancy. Most of these unfortunate occurrences are due to aneuploidy also. Implantation occurs, HCG hormone is produced but often the progesterone level is low, the HCG hormone does not rise and over the first week of the pregnancy it is apparent that the pregnancy is in danger, and then the hormone levels go down over the following week. In essence this may be considered a microscopic miscarriage. A tiny defective implanted embryo is lost which contained placental cells and usually had no fetal development at all.
Thomas FH and Vanderhayden .  Oocyte growth and developmental competence in In –vitro Maturation Of Human Oocytes Tan, Chian, Bucket eds. pages 1-15  Informa UK 2007
Harris, Sarah E and Picton HM. Metabolism of follicles and oocytes during growth and maturation. IBID  page 15-36.
Written by Joe B Massey MD
Additional references provided on request.
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Birds, Bees and Bunnies: The Biology of IVF – Part 1
Birds, Bees and Bunnies: The Biology of IVF – Part 2 (Eggs!)


Birds, Bees and Bunnies: The Biology of IVF – Part 2 (Eggs!)


This article discusses the basic biology behind the process of In Vitro Fertilization (IVF) and may be helpful to couples who plan to undergo IVF. Technical terms may be found in a glossary at

CNY Fertility Center has locations in Syracuse, Albany and Rochester, NY. CNY Fertility Center offers couples and individuals affordable fertility treatments including low cost IVF (In Vitro Fertilization) by our experienced and caring staff.
Now let’s look at the details of the process from the perspective of the biology of reproduction. How does a woman conceive? Only 5% of all the eggs harvested in IVF treatments result in a baby.  Many of the errors which arise can be traced back to the egg. The most obvious example of this is the well known adverse influence of advanced age of the woman. In many instances an egg from a 40 year old will look great under the microscope, but it is doomed from the start by genetic errors. Please refer to a separate article on IVF and age of the woman. The resting egg within the primary follicle is surrounded by a single layer of cells, the granulosa cells. Selected follicles grow to become secondary or antral follicles in a phase called initial recruitment. This occurs before the woman even has a period. Then suddenly a new phase of recruitment begins with the onset of the menstrual cycle.  Much research has been directed at the signals which initiate the selection of about 20 follicles to suddenly begin to grow at once. As yet this signal is not clearly identified. But in any case, independent of gonadotropins, this cohort of follicles does emerge. As they grow they do become sensitive to the gondadotropin (gonad /growth)follicle stimulating hormone, FSH. In IVF, added gonadotropin will be given by injection to promote the growth of these follicles.

Primary follicle
The granulosa cells multiply and as the follicle develops, fluid is secreted forming an antrum which can be visualized on ultrasound as it reaches about 2 mm in size. Counting the number of these antral follicles can be predictive of the numbers of eggs retrieved in IVF cycles.

Secondary or antral follicle surrounded by granulosa cells. From
About half of the antral follicles will result in an egg in the laboratory during IVF. The numbers will vary from one month to another, but typically within a narrow range. One does not see the antral follicle count jump from 3 to 15 in one month.   There is no amount of drugs which can force more follicles to develop than there are antral follicles. The limit is really set at the beginning of the cycle.  Counting the antral follicles is probably more valid than the measurement of blood FSH on day 3, in evaluation of fertility potential.

Mitochondria from
Another problem which can arise as the cytoplasm begins to mature relates to the tiny energy factories themselves, the mitochondria. Yes, those were in your biology book too. The mitochondrial numbers increase enormously from about 10,000 in the primordial egg, to several hundred thousand in the mature egg.  The mitochondria are the tiny engines which burn or oxidize fuel and produce energy for the egg. In older women, eggs may have low numbers of mitochondria.  This may be an aspect of the eggs’ incompetence. Attempts in the past to restore mitochondria by injection of healthy cytoplasm from egg donors have not been successful.    For complex reasons this research area is not being pursued.
The all important FSH hormone stimulates the development of the cumulus cells which are tightly bound to the egg and provide nutrients and molecular signals. These assist in rapid growth of the egg cell from 35 to 90-120 microns in diameter as it acquires the proteins and RNA which will be utilized in fertilization and development.
In IVF, the immature egg is easily recognized by the presence of the nucleus (germinal vesicle). Once it disappears, we know that maturation is occurring.

Germinal Vesicle Egg
In the meantime, a tiny amount of LH is required to initiate the breakdown of the nucleus, (germinal vesicle breakdown) which marks the beginning of nuclear maturation and the egg evolves to the stage known as Metaphase I.

MI egg
The development of the nucleus must be coordinated with simultaneous development of the cytoplasm. Estrogen provided through the cumulus cells helps to activate or suppresses selected genes in the cytoplasm. These lead to the maturation steps required. Just the right amount of estrogen is needed, and this hormone production becomes the marker used for follicular development. Daily blood tests can indicate indirectly that the follicles are producing estrogen well or not so well.
The other ovarian hormone, progesterone is involved in egg membrane and cytoplasmic maturation as well (Chian review). If there is a surge of LH, the process of luteinization can begin in the follicle, causing production of rising progesterone levels. Too much progesterone from premature luteinization can occur and this causes atresia of the eggs and all is lost. This is the reason in IVF the pituitary gland is usually suppressed by the agonists or antagonists.  See further discussion of antagonists at and elsewhere on this website.

Simultaneously, one other element of maturation occurs at the level of the membrane around the egg. Cytoplasmic maturation coincides with one more element. The membrane surrounding the cytoplasm has to mature. Most amazing at the submicroscopic level is the critical cortical granule release system. When one sperm enters the egg, this system instantly solidifies the membrane and prevents entry of another sperm.

Granulosa cells communicate with the egg by tiny projections which create an intimate relationship. These cells must remain attached to the immature egg so that nourishing factors are transmitted which promote the development of the cytoplasm. The cytoplasm, the bulk of the egg, contains the submicroscopic mitochondria and other organelles. The maturation of the organelles must occur hand in hand with the maturation of the nucleus. IVF patients will recognize the cytoplasm as the major part of the egg, the place where sperm are inserted with a needle in intracytoplasmic sperm injection, ICSI.

Later, when the egg is mature, the granulosa cells are washed off with an enzymatic solution.  Then we can grasp the egg with a pipette and inject a single sperm (ICSI). This will be covered later.

These connections are not a one way street from cumulus cell to the egg. The egg in turn is controlling or influencing the functions of the rapidly expanding group of surrounding granulosa cells. It is sending signals which promote the very development of the follicle which expands eventually to approximately 2 cm. Some of the cells are morphed into theca cells, and later will be called on to produce progesterone.  This dynamic expansion has no rival in the body. The rapid development of the needed blood supply is another of the diverse and intricate responses required.

During stimulation in IVF, high doses of FSH and sometimes LH are used to recruit multiple follicles and aid in their maturation. For many years there has been concern that gonadotropin stimulation and the effect on the oocytes could be a factor which limits the success of IVF (Paulson et al 1991). The blood supply is impaired by crowding of follicles when we stimulate for IVF. Low oxygen within the follicle leads to lower oocyte competence in some of the eggs. This is one disadvantage of ovarian stimulation (Von Blerkom 1997)
Van Blerkom ( 1997) and Munne  (1997) suggested that drug stimulations might predispose to chromosomal abnormalities in the human embryo. Jackson et al (1998) asserted that accelerated ovulation induction response was linked to abnormal nuclear formation which resulted in embryos with a defect called multinucleation.

On the other hand there have been many studies reassuring us that the outcomes of IVF are not revealing an epidemic of abnormal babies. Furthermore, reassuring results were noted recently in a comparison of stimulated vs natural cycle derived oocytes (Zeibe et al, 2004). Most likely these embryos which become impaired are falling by the wayside and never implant.
But let’s get back to the biology of the cumulus-egg complex. In addition to links to the cytoplasm,   there is an active two way communication from the cumulus involving nutrients and signals to the nucleus to begin its required maturation steps. This begins the process which results in the transition of the nucleus from the packed short chromosomes of the germinal vesicle of the most immature egg, to the metaphase II mature structure which is ready for fertilization.

In the natural cycle, the dominant follicle produces androgens (Anderiesz, and Trounson, 1995) which cause atresia, a type of cell death of the remaining follicle and eggs.  Additionally, the rising level of estrogen signaling through the inhibin-based feedback mechanism tells the pituitary gland to reduce the level of FSH which reaches the smaller follicles. These follicles are thus deprived of the stimulation they need to continue to grow.  Thus in most cycles after the largest follicle is about 14 mm, only one egg retains the competence to become fertilized and develop. The concept of acquiring healthy eggs for in vitro maturation (IVM) rests on appropriate harvesting of oocytes after maturation has begun and before atresia has begun. In any egg retrieval, there are likely to be one or more eggs which are atretic.

Atretic egg
Once the follicles have been recruited, the stimulation by FSH is necessary for continued growth. But the timing and amount of FSH can be critical (Thomas and Vanderhayden). Premature stimulation can interfere with egg competence including errors in the chromosomes.

In IVF, ovarian stimulation overrides the influence of the dominant follicle. We promote the continued development of all the follicles by giving FSH in huge doses relative to the amount naturally produced by the pituitary.  This is called stimulation or hyperstimulation of the ovaries and is a key to IVF.

An important function of the granulosa cells as they relate to IVF is the fact that these little cells are powerful factories producing estrogen. As mentioned earlier this is need to promote the development of the egg. The healthy follicles produce one particular type of estrogen called estradiol in science language, but called E-2 in the IVF clinic. Normal follicles produce dramatically increasing amounts. Unhealthy follicles produce less. The total amount of E-2 can be measured in the blood as an indicator of the response and health of the follicle. This indicator ultimately reflects on the health of the eggs.  Additionally too much estrogen being produced can be an indicator of the possibility of ovarian hyperstimulation, a dangerous syndrome in about two per cent of IVF cases.

As the egg matures the chromosomes numbers are reduced to half of an adult cell and the egg is ready to receive a contribution of DNA or genetic material from the sperm.

The final trigger for resumption of nuclear maturation and competence in IVF treatment is the result of the surge of LH like activity provided by its chemical cousin, HCG. Suddenly the close bond between the granulosa cells and the follicle are broken. The egg in cumulus is preparing to be cast off down the tube to meet a sperm and the final nuclear development occurs as the magical metaphase II stage is quickly reached. At this point the egg has half the copies it will need as it has cast off 23 copies of its DNA into the polar body. The observation of the polar body is the sign of maturity is welcomed in the IVF lab as the signal that the nucleus has reached this stage.

Mature egg with granulosa cells in IVF
Egg with granulosa from


Sperm from

MII, as seen in the IVF laboratory with prominent polar body

M II with nuclear material in the polar body and nucleus (blue) from
In the IVF lab the ideal egg is the metaphase II which is abbreviated MII using roman numerals, “M two’s” as we call them. The polar body is easily seen once the granulosa cells have been stripped away.

If the first cell division goes awry, the wrong number of chromosomes results. The errors in general are known as aneuploidy. One possibility is that the egg retains one chromosome too many. This is called trisomy, three of one set of chromosomes. Down’s syndrome is caused by triploidy of the number 21 chromosome for example. Many miscarriages are due to trisomies of certain chromosomes. Another derangement of numbers is monosomy (one /chromosome), in which the egg is left with one copy of the pair required for normal reproduction and development. Turner ’s syndrome and some miscarriages are due to monosomy.
Often fertilization can be accomplished by simply allowing the sperm and eggs to mix in vitro. The other prominent structure in the egg is the zona pellucida (clear zone) or jelly coat, which must be traversed by the sperm and usually does so with ease in natural fertilization. The natural process is depicted in a clip graphically:

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Birds, Bees and Bunnies: The Biology of IVF – Part 1


This article discusses the basic biology behind the process of In Vitro Fertilization (IVF) and may be helpful to couples who plan to undergo IVF. Technical terms may be found in a glossary at

CNY Fertility Center has locations in Syracuse, Albany and Rochester, NY. CNY Fertility Center offers couples and individuals affordable fertility treatments including low cost IVF (In Vitro Fertilization) by our experienced and caring staff.
In the high school classroom, perhaps we giggled a bit about these slightly embarrassing topics. Now that we are trying to get pregnant we need to pay attention.  The story of reproduction is fascinating and complex and the more we know the more we can understand some of the terms used in IVF clinics which affect our outcomes.

In nature, for most women, the production of a single egg each month is automatic. The hormone changes required are treated lightly here.  In IVF, we must go to enormous lengths to be able to obtain this precious cell (the egg) in the laboratory.  More of the story can be found in articles on how the gonadotropin hormones work and how egg retrieval is done, elsewhere on this web site.

We begin with consideration of the egg, which measures a tenth of a millimeter, is barely visible, but is the largest and most complex single human cell. It provides the energy and structure to form a healthy embryo which can develop into a baby composed of a few trillion cells.  A perfectly competent egg is ready to be fertilized and develop to the 4 cell stage with a little help from the sperm. The sperm will provide 23 chromosomes, half of the genes and the centriole, critical to organize cell division. But (as some would argue, typical of the man), there is no energy provided by the sperm nor is there any follow-up responsibility. The leading contributions for assuring a next generation must depend on the egg.

The tiny egg which has been resting in the ovary for 20-40 years must suddenly, within weeks, awaken, mature and develop the ability to combine with the sperm and divide.  Rapid and complex changes give the egg competence to do these tasks.  The more we know about the complexities of the process it seems amazing that it ever works. Indeed, too often it does not.  There is much inefficiency in reproduction, especially in humans. The development of the eggs, the fertilization process, and early development often fail in nature. Even the most fertile young woman has about a 20% chance to conceive in one cycle.  Throughout evolution this has turned out to be just fine for the human species. Other animals are different. Famously the rabbit produces several eggs each month, and to make sure the timing is right the female bunny, the doe, ovulates by reflex after intercourse. Pregnancy follows automatically. Considering our behavior, it is a good thing that this is not the case in humans.

However the good luck of the bunny is not helpful to infertility patients, who are often frustrated with the low percentages which can be less than 5% per cycle.  They have to spend time and money to improve their conception possibilities. In fact after IVF, ongoing healthy pregnancy rates can be in the range of 40% in one month.  There is much technology involved to produce multiple eggs and embryos.
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Birds, Bees and Bunnies: The Biology of IVF – Part 2 (Eggs!)
Birds, Bees and Bunnies: The Biology of IVF – Part 3 (Sperm & Embryos)


IVF and Drugs from Goats and Rabbits


Presented by CNY Fertility Centers in Syracuse, Albany and Rochester New York.  Our services range from infertility diagnosis for couples trying to conceive, to advanced techniques for conventional and low cost IVF. This news article is not directly related to treatment of women trying to conceive , but is of general  interest and touches on the technologies we use in infertility treatment.

Humans have used plants and animals as natural sources of drugs since prehistoric times. The basic ingredient in aspirin dates to the discovery of the healing properties of the bark of the willow tree. Pigs were the main source of insulin for diabetes for a generation.  Mankind has always bred both plants and animals to improve their commercial value. More recently biotechnology has allowed modifications of plants so that they grow faster or fight disease. The latter properties are not possible from breeding alone.  Genetic material can be injected into seeds so that the plants will grow up and resist the fungus. There are also plants that are genetically modified to produce products such as antibodies and enzymes used in chemistry.

Changing the genetic properties of warm blooded higher animals to benefit mankind presented new challenges to scientists. After many others failed, Dr Ralph Brinster at the University of Pennsylvania and his diligent staff found the method which finally worked. Someday he might be a Nobel Prize candidate because his work in the early 80”s has now enabled others to produce the first approved drug to be approved for human usage. Now let’s look at why this work was done and then explain how IVF was used as the basis for this leap into the future.

Most drugs used everyday are relatively small molecules and can be synthesized. A familiar example is synthetic thyroid hormone for low thyroid conditions. Synthesis is the method used for pharmaceuticals for most of the last century. Most of these are administered in pill form.

Some hormones that we need to administer in human treatment are large and complex in structure. Examples are insulin and gonadotropin like the pituitary hormone follicle stimulating hormone or FSH.  The FSH which is now made by recombinant technology is the relevant example for women who are trying to conceive. Used in stimulation of the ovaries in infertility therapy like IUI and IVF It is a protein with a complex structure and it can’t be synthesized. For years the only source was from the urine of menopausal women. At first it was allegedly from nuns in Italy, but the demand required much more than the convents could supply. Now the modern method of FSH for infertility treatment comes from cells derived from Chinese hamsters. The cells are injected with the DNA for FSH. This tricks them into producing human FSH. Millions of cells are cultured in huge vats. This now enables production of more FSH for infertility patients than could be practically derived from urine. Further, the FSH is much more pure.

FSH, a large complex protein
This now routine method of biotechnology, involves inserting DNA into cells like bacteria or hamster cells by the billions and producing drugs in huge sterile vats. Then the desired product has to be extracted and purified. In order to do this on large scale, a cell culture biotech plant can cost hundreds  of millions of dollars

There are some cases of drugs which might be best made by a new technique of genetic modification. This method is called transgenic when applied to living animals.  It has been done to improve the growth characteristics of baby fish.  DNA for growth hormone injected into the eggs of fish enables the fry to grow much faster. This is good for growing fish on a farm. It is not free because the baby fish eat more that their genetically un-enhanced peers, and we don’t want them getting out into the ocean, and reproducing and eating all the other innocent fish, so they have to be sterile.

Transgenic fish with high growth hormone compared to normal
There are certain disease conditions which require a protein drug but which don’t require large production. Thus there is not a big market to support the cost of a big production facility. So why not use transgenic animals to make proteins which can be made for less than half the cost. The investment cost is down to tens of millions. It still is not cheap to get the desired molecule out of the milk and purify and sterilize and package it and then invest in a very expensive series of clinical trials to prove it works.
Once the hormone is produced it must be purified and the extraction steps are similar.

These attempts to bring Brinster’s advances to the production of drugs have been funded largely by venture capital for years. It has been a long and dusty road. The group in Scotland which tried transgenics also funded the work on the first cloned sheep, Dolly. They are not in business any longer, nor are many other transgenic start-ups.

Another small company, GTC Biotherapeutics identified a drug which needed a biotechnology solution, Antithrombin which is used for an uncommon clotting disorder until now has been obtained only by extraction t from blood plasma. By the use of transgenics, now one  goat can produce as much antithrombin as can be extracted from 90,000 pints of blood. Now this new method provides a safe reasonably economical and stable source of antithrombin for this rare disease.

Other examples of transgenic “pharming” which are in the pipeline include a drug used for a rare hereditary form of edema.  Since you don’t need much of this to supply the world it will be produced in the milk of rabbits in Sweden. PharmAthene is using transgenic goats to produce stockpiles of a nerve gas antidote.

The techniques
The first step is to take advantage of the access to the beginnings of reproduction the embryo in the lab by doing IVF. This miracle of modern science is done easily now.  The scientists took genes for antithrombin and linked them to milk production genes . The genes were then injected using a microscopic needle into the one cell embryo.

Then the embryo was implanted into a surrogate goat. The kid was born, matured, was bred and then after she gave birth, she produced milk which contained antithrombin along with casein and other milk proteins. Thus some of the protein production of the milk has converted to produce a molecule which is useful for medicine. This success came after a number of failures.  Finally one of the goats produced a high level of the desired protein. In the future, the offspring  which have proven to be producing the best will be mated and their offspring will carry the trait and produce the product also. In this manner, a herd of modified goats can be raised.  All of this can be done for $50 million, far cheaper than the hundreds of millions needed for a biotechnology production facility.

In the future transgenic pharming may be the method of choice for a host of products for uncommon and rare diseases.


IVF and Progesterone Treatment


The following information is provided by CNY Fertility Centers in Syracuse, New York, Albany New York and Rochester New York. Low cost IVF and other infertility treatment is available along with an extensive range of holistic methods.

After ovulation, progesterone is produced by the corpus luteum, which comes from the follicle. This steroid hormone induces the lining of the uterus to support implantation and growth of the embryo.  For up to 8 weeks after the missed period, or 8 weeks gestation as physicians refer to it, the secretions of the corpus luteum are necessary. During the next week, the placenta produces enough progesterone to support the further development of the pregnancy. This is known from experiments 30 years ago involving removal of the corpus luteum during pregnancy.

Measuring progesterone levels in a menstrual cycle or in pregnancy are not very useful because of wide variations in output. A syndrome known as luteal phase defect is thus very difficult to diagnose.  Progesterone levels in pregnancy below 10 ng/ml are commonly associated with a poorly implanting pregnancy. These may indicate an impending miscarriage or tubal pregnancy.
In IVF, the follicles are aspirated with a needle, removing many of the cells which might be there otherwise to form the corpus luteum. Thus, since the early days of IVF, progesterone supplementation has been used to make up for the deficit created by removal of these cells.

The problem of questionable progesterone availability was further aggravated by the use of the gonadotropin-releasing hormone analogs. These drugs, Lupron, Antagon and Ganerelix, suppress the pituitary’s production of LH, cutting stimulation of the corpus luteum and thus cutting progesterone production. It is clear that progesterone supplementation is needed after these drugs are used, as they are in virtually all IVF protocols today.

Progesterone can be used after IVF treatment by either injection or vaginally. There has been a long and deep controversy regarding the use of the vaginal approach. Two key US studies showed that it did not work as well as injection and the painful progesterone shots became the norm in the US for the past 10 years. Further study however has now shown that clinical pregnancy rates after IVF are the same no matter which route is used.

It is also clear that supplementation is needed up to 7 weeks gestation and almost certainly not needed beyond 9 weeks gestation. The exact point is not known.

Vaginal options include gels and tablets approved for usage in infertility and IVF. These include Crinone which can be used once a day. It has been extensively studied and shown to be as effective as the progesterone shot. Others are Endometrin tablets and Prometrium tablets.

Although there has been some concern on this point, it appears that there is no evidence that the use of progesterone poses risks to the fetus.

Practice Committee ASRM SRE.  Progesterone supplementation during the luteal phase and in early pregnancy in the treatment of infertility Fertil Steril 2008


Solo Mothers


IVF in single women with donor eggs and donor sperm
CNY Fertility Center has locations in Syracuse, NY Albany, NY and Rochester, NY. Fertility treatments are affordable and include low cost IVF (In Vitro Fertilization). Our caring and experienced staff provides confidential treatments for heterosexual couples, same sex couples and  unmarried individuals who are looking to conceive. CNY Fertility Center offers donor eggs, donor sperm and donor embryos. In this article we will explore the options for solo mothers using donor eggs and sperm IVF to create their family.

There is virtually no method for trying to conceive which has not been explored in this day of increasingly progressive options. There can be many different match ups between the sources of the sperm and eggs, thanks to the structure of the IVF technique. It seems that where there is a will, there is a way.

Over the past 20 years, the new class of “solo mothers” has emerged. This is an example of the strength of the drive for reproduction, despite seemingly overwhelming odds. One study focused on 11 single Israeli women who required both eggs and sperm from anonymous sources. These women’s biological clocks had indeed run out, as their average age was 46. Prior to treatment, these women were intensively interviewed regarding issues of older parenting and the living adjustments that would have to be made.

In most countries, it is only financially stable women with college educations who choose to become mothers in this fashion. In pro-baby Israel, the national health care system actually encourages this further, as it provides infertility treatment for producing up to two children up to the maternal age of 51, without regard to marital status. Out of the small Israeli study group, three women had not attended college.  Upon follow-up, socio-emotional development and mother-child relationships seemed satisfactory. All the women reported the highest possible levels of satisfaction with parenthood.

Several of these women were working full time; however, they were depending on extended families and day care facilities during those hours. Interestingly, the lack of a genetic bond did not seem to be a concern for the women: The gestational bond seemed quite strong and was distinguished from adoptive situations. This information may be of help to others considering egg donations.

It is known that IVF can produce multiple births, and this may carry some health risks for the children. In the small Israeli study, one set of twins had suboptimal health after a premature birth.  Certainly this risk is an important one to remember, if a single parent. The amount of work and time involved may be greater than “normal,” if circumstances such as this arise. Replacement of single embryos is a consideration for women in this situation. And that might mean an increase in the number of attempts to have a child; therefore, it might increase IVF cost.

Methods of low cost IVF can be applied in the pursuit of conception for the single woman. Egg donors may have low gonadotropin stimulation for fresh cycle therapy. Egg banks using frozen eggs are also now a realistic option to pursue. This is because the splitting of batches of donated eggs among two or more recipients lowers the cost of IVF.

There is debate on what to tell the child. Concerns have been raised about the previous secrecy involved and much increased openness with the children has been advocated. This and other related topics are covered in a recent book by Angela Best Boss and Evelina Sterling. It is of note that the writers provide a professional counseling service at   Also we recommend the referenced article published in Women’s Health on a related topic.

Best-Boss, Angie and Sterling, Evelina. Having Your Baby through Egg Donation  2005.
Kirkamn M.  Egg and embryo donation and the meaning of motherhood.  Women’s Health 2003; 38: 1-18.
Landau R et al. Older single mothers and IVF with sperm and egg donation. Fertil Steril 2008; 90: 576-583


Embryo Transfer – Day 3 versus Day 5


CNY Fertility Center has locations in Syracuse, NY Albany, NY and Rochester, NY. CNY Fertility offers affordable fertility treatments including low cost IVF (In Vitro Fertilization). Patients often have questions about the day that their embryos will be transferred back to their uterus following their IVF procedure. This article is a quick summary of the history and advantages of both Day 3 and Day 5 embryo transfers.
Until about 10 years ago, all embryos were routinely placed in the uterus on day 3 of the cycle. Embryos are then at the 6-8 cell stage.

(8 celled embryo – Day 3)
Culture methods then emerged which allowed healthy embryos to continue developing to day 5, the blastocyst stage which has several attractive features.  Most importantly it allows some of the embryos which are doomed to failure due to internal defects to fall by the wayside as they arrest and do not continue to develop. Thus the more hardy embryos are self selecting and the rate of implantation of each embryo is higher.  Culturing embryos out to the blastocyst stage reduced the number of embryos that were transferred back as well, reducing the incidence of multiple gestations.

(Blastocyst stage embryo – Day 5)
Initially it seemed as this was applied in IVF practice, that the ability to choose the more robust embryos by self selection in this manner would raise pregnancy rates. In a common scenario, the choice if a patient had 5 embryos available for transfer, all about equal in quality on inspection under the microscope, the option would be to replace 3 embryos on day 3 or two on day 5. It was hoped that the day 5 embryo transfer would yield higher results for the IVF patient. This has not turned out to be the case. It is however true that the number of triplets is reduced by use of the day 5 strategy, which is an important option to consider when the risk of multiples is paramount.


IUI with Clomiphene, a First Line Treatment for Infertility


This information is provided for couples who may just be starting out in fertility treatments and are trying to conceive using IUI with clomiphene. CNY Fertility Centers provide infertility services including low cost IVF (In Vitro Fertilization) for couples who are starting or continuing their families in Albany, New York, Rochester New York and Syracuse, NY. In addition to our local services we work with patients from across the country and world offering affordable IVF and fertility treatments.

Unexplained infertility is when a couple can’t conceive although the woman is ovulating, and her fallopian tubes, uterus and partner’s semen results come back normal after testing. Some of the women have had endometriosis diagnosed and treated, thus are not truly unexplained, but do fit into this category in terms of an approach for treatment.

Clomiphene is inexpensive, and acts in women who already ovulate to stimulate production of several eggs during a treatment cycle. Clomiphene causes the brain to misinterpret blood estrogen levels. This induces the pituitary gland to produce a surge of the follicle stimulating hormone or FSH. The result is the production of more than usual numbers of follicles, each with one egg.  Intrauterine insemination (IUI) places more sperm into the uterus and then the fallopian tubes than could ever reach through intercourse. Thus more bullets are shooting at more targets.

The combined use of clomiphene and IUI has been shown to nearly double the results compared to using clomiphene alone to improve pregnancy likelihood (Guzick, 1998). The master student of IUI, Dr Richard Dickey and colleagues in 2002 compiled a large series in New Orleans and reported almost 10% success per cycle.

The distinguished Boston IVF group in a study led by Dr. Alan Penzias recently confirmed a cycle success rate of 11.5% (Dovey, 2008) from over 4000 cycles of treatment. The patients were ovulatory and some of the men had low sperm counts.  The success of treatments cumulatively over up to four cycles, was successful in 24% of patients under age 35. Age specific pregnancy rates per cycle ranges from 12% under age 35 to 4% over age 40. Corresponding decreases in overall success were seen according to age. Only one patient was successful (1.8%) of the 55 women treated over 43 years of age.

The study verified findings by others who found that 90% of success is found in three or four cycles. Those who are not pregnant by then should move to gonadotropin and IUI or IVF therapy.

At RBA in Atlanta, Dr Massey and colleagues found that the addition of a chemical called PAF to the sperm wash dramatically improved success rates (Roudebush 2004) to nearly double those without it. This is a reasonably simple method which more clinicians might use.

Those who are concerned with cost effective treatment for infertility continue to believe that clomiphene and IUI are a good treatment for younger patients who are trying to conceive, and fit the criteria outlined.

Selected References
Dovey S et al Fertil Steril 2008:90:2281-86
Guzick, DS et al Fertil Steril 1998;70:207-13
Dickey RP et al Fertil Steril 2002;78:1088-95
Roudebush WE et al Fertil Steril 2004;82:52-56


Gums and Gremlins: Endometriosis Research Update


Gums and Gremlins: Endometriosis research update.
This information is provided for couples who are trying to conceive and have an interest in endometriosis research. For further information on this complex disorder see the information on this website and link to The association has a focus on research into dioxins in the environment and the link to this disorder. This article is provided by CNY Fertility Centers in Rochester, NY, Syracuse, NY and Albany, New York.

International findings from endometriosis research were grouped into the February 2009 issue of Fertility and Sterility, the journal of the American Society for Reproductive Medicine.   Perhaps the most innovative came from China. Levels of Gremlin 1, an oddly named chemical antibody, were found to be elevated the blood of women with endometriosis. This is a highly specific test which relates to growth of small blood vessels such as occur in the endometrium. It is hoped that this could develop into a biomarker for the disease which is a common cause of infertility. Currently only laparoscopy is definitive in diagnosing endometriosis. Other biomarkers are being explored but have not proven to be specific. Sha G et al. Elevated levels of gremlin-1 in …patients with endometriosis Fertil Steril 2009; 350-37.

In a study of interest from the University of Michigan, the link between two diseases which involve inflammatory processes were explored. The odds of having gingivitis inflammation of the gums were 57% higher than normal if a woman had endometriosis. Both diseases involve altered immune response. Interestingly preterm labor is among several disorders associated with gingivitis. Further, women with endometriosis and gingivitis have increased incidence of other autoimmune diseases such as asthma, lupus, and multiple sclerosis. The term global immune dissociation has been used. Kavoussi SK et al Periodontal disease and endometriosis Fertil Steril 2009; 91:335-342

A team for Florence Italy explored the reduced immunity which allows endometrial cells to implant in the pelvis in women who have endometriosis. It is normal for cells shed form the endometrium to travel out the tubes and into the pelvis during menses. In 5-20 % of women, there may be an immune defect in the peritoneal cavity which allows those cells to grow. It has been shown that the endometriosis patients have decreased natural killer cells and T cells. A special messenger peptide called CXCL10 has been found to be low in the blood and abdominal cavity in women with endometriosis. Galleri L, et al Low serum … CXCL10… in endometriosis. Fertil Steril 2009;91:331-334

Perhaps the reduced immunity which allows endometriosis to occur also predisposes to gingivitis and other disorders.
Editor, Joe B Massey MD


The high cost of increasing age and FSH in IVF treatment


This article is provided for patients who are trying to conceive and have concerns regarding the potential cost- effectiveness of IVF. It is written for patients who have an understanding of the basic concepts being discussed. For explanation of the significance of FSH values, please see articles on this website on IVF and prognosis, and low response. At CNY Fertility Centers, access to care is a concern addressed by offering low cost IVF options in Syracuse, New York, Rochester NY and Albany NY.

The age of a woman who is trying to get pregnant with IVF and her ovarian reserve as reflected in day 3 FSH values are good predictors of IVF outcomes. Henne and colleagues at Walter Reed Hospital and the NIH evaluated 1238 first IVF cycles of women between age 26 and 42 years and an FSH level of <13 miu/ml.  A cost analysis was applied and focused on these patients who by normal standard were good prognosis. Patients need to understand that statistics for overall success even with a specific age group may not apply if the FSH is higher than 12 as results would be even worse. At a cost of $10,803 per cycle costs soared to over $100,000 per baby born as FSH and age of the patient increased over age 38-39.
This is not surprising as Voorhis had estimated cost per baby of $89,981 for patients over 38. Trad calculated the cost to be about $75,000. Neumann, who used very low success rates estimated that in low prognosis patients, costs per baby could be as high as $800,000.

For comparison and for patients concerned about the high cost of donor egg treatment the delivery rates of the alternative must be considered. At a cost of $25,000 per cycle, and delivery rate of 51%, the cost per baby is $49,000. These costs will be dropping rapidly as egg banking becomes widely available. As a woman’s predicted delivery rate falls below 10%, the donor egg option becomes favored treatment economically. CNY Fertility Center offers multiple options to make IVF and donor eggs more affordable including a refund program for IVF and donor egg IVF, 0% financing, six cycle discount program, and Fall IVF specials.

Henne, MB et al The combined effect of age and basal FSH on the cost of live birth at assisted reproductive technology Fertil Steril 2008; 89:104-10.
Neumann, PJ Johanesson M The willingness to pay for in vitro fertilization: a pilot study using contingent valuation. Med Care 1994; 32: 686-99.
Trad, FS et al In vitro fertilization: a cost effective alternative for infertile couples? J Assist Reprod Genet 1995; 12 418-21.
Van Voorhis BJ et al. Cost effectiveness of infertility treatments. Fertil Steril 1997; 67:830-6