We should talk. If interested, please contact my assistant, Patti Converse at 702-533-2691 to set up an online consultationGeoff Sher

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Prolactin is a protein hormone (closely related to human growth hormone) that is secreted by specialized cells in the anterior part of the pituitary gland. In addition, the hormone is also produced and secreted by a broad range of other cells in the body, most prominently various immune cells, the brain and the lining of the uterus. Most cells respond to prolactin. In fact, it is hard to identify any tissue that does not have prolactin receptors.

Although prolactin’s major target organ is the breast where it stimulates development and milk production, the hormone has many other functions. Several hundred different actions have been reported for prolactin and

Immune cells are rich in prolactin receptors and certain types of lymphocytes in fact synthesize and secrete prolactin. These observations suggest that prolactin may to some extent act as a regulator of the body’s immune activity.

In an area in the brain known as the hypothalamus, a chemical called dopamine is released. Dopamine suppresses prolactin synthesis and release by the pituitary gland. As such it acts as a “hypothalamic brake set” causing prolactin only to be secreted when the “brake” is released. Treatment with dopamine agonists such as bromocriptine (Parlodel) and cabergoline (Dostinex) , by enhancing serotonin production lowers prolactin

Several other hypothalamic hormones, including thyroid releasing hormone (TRH) and gonadotropin releasing hormone (GnRH) cause an increase in prolactin secretion Stimulation of the nipples (including but not limited to nursing) leads to hypothalamic activation and prolactin release Estrogens also exerts a positive control over prolactin synthesis and secretion

Even modestly raised prolactin levels (20ng/ml-40ng/ml) can interfere with estrogen-induced endometrial proliferation as well as egg/ ovarian follicle growth and development. Accordingly treatment with dopamine agonists (bromocriptine/ Cabergoline) might be of benefit in such cases.

Increased PRL secretion reduces the pulsatility of GnRH impairing the pituitary production of FSH and LH and may directly impair the endocrine activity of ovarian follicles as well as endometrial response to estrogen. This can lead to dysfunctional or failed ovulation, a defective luteal phase, and a poorly developed endometrial response to estrogen (a thin endometrial lining). About n 5% of unselected, asymptomatic infertile women have hyperprolactinemia. In such cases long-term use of dopaminergic drugs such as bromocryptine and can normalized prolactin levels leading to reestablishment of functional ovulation and improved endometrial development. About half of the pregnancies occurring during dopaminergic therapy start after the first 6 months of this drug therapy. Treatment should continue for at least 1 year.

Common manifestations of significantly increased prolactin secretion (hyperprolactinemia):

• In women:
  • Oligo/amenorrhea (reduction or absence of menstrual flow) and galactorrhea (excessive or spontaneous breast secretion of milk).
  • A modest elevation in blood prolactin can also point to an underlying state of hypothyroidism
  • Markedly elevated prolactin levels (i.e. >60ng/ml) might point to a prolactin producing pituitary macroadenoma or microadenoma as well as other intracranial lesions such as craniopharyngiomas, meningiomas etc.
• In men: Such men rarely have galactorrhea
  • Hypogonadism,
  • Breast enlargement (gynecomastia)
  • Erectile dysfunction
  • Decreased Libido
  • Sperm dysfunction resulting in infertility and with impotence.

Causes of hyperprolactinemia: Main causes of pathologic hyperprolactinemia (40).

• Idiopathic (commonest variety) ….cause unknown Acromegaly
• Empty Sella Turcica
• Renal Failure
• Polycystic Ovarian Syndrome (PCOS)
• Certain drugs:
  • Antipsychotic drugs ( phenothiazines, haloperidol, monoamine oxidases (MAO) risperidone, fluoxetine, butyrophenones,
  • Anti-emetics: metoclopramide, domperidone,
  • Tricyclic antidepressants
  • Opiates
  • Verapamil
  • Antihypertensives and Ganglion blockers

Drug-induced hyperprolactinemia can be reversed by modifying or withdrawing the causative medication. In cases where this cannot safely be done, bromocryptine derivatives can be used.

• Pituitary adenomas (prolactinomas)
  •  Some pituitary adenomas are treated by surgical removal but in most case prolonged treatment with bromocryptine or cabergoline will effectively lower blood concentrations and lead to shrinkage/disappearance of the tumor. Such treatment is also safe during pregnancy.
  •  Intracranial lesions such as craniopharyngiomas, meningioma causing hyperprolactinemia are usually treated by surgical removal.

Hyperprolactinemia and Reproductive Dysfunction:

• Hypothyroidism in women is often caused by an autoimmune process where antithyroid antibodies progressively replace thyroid glandular tissue with functionless connective tissue. In roughly 50% of such cases there will be increased uterine natural killer cell activity (NKa) which may profoundly impair implantation leading to “perceived infertility” or recurrent pregnancy loss. Thus, ATA with NKa can be present prior to the development of clinically overt autoimmune hypothyroidism (Hashimoto’s disease). Since women with NKa are often infertile, or experience recurrent pregnancy loss, it is important that any unexplained hyperprolactinemia associated with reproductive failure or infertility be evaluated for an immunologic implantation dysfunction (IID) through testing  for the presence of antithyroid antibodies and if the ATA level is elevated, that an NKa test (K-562 target cell test) be done. What is not often commonly recognized is that even in cases where autoimmune hypothyroidism is clinically overt, treatment with thyroid hormone replacement will usually not solve the reproductive dysfunction which will usually require selective immunotherapy with Intralipid (IL) infusions plus steroid therapy. IL is administered intravenously about 4-7 days prior to ovulation or egg retrieval and then repeated one more time upon biochemical confirmation of early pregnancy. The steroids are continued to the 8^th  week of pregnancy and then tailed off over 2 weeks.

• Ovarian Hyperstimulation Syndrome (OHS): Prolactin facilitates production by ovarian follicle cells of VEGF (a vasoactive substance that increases vascular permeability of blood vessels) In cases of severe ovarian With severe ovarian hyperstimulation syndrome (OHSS) where there are a large number of follicles present (>25) and the blood estradiol level is markedly elevated (4,000pg/ml), even modestly elevated prolactin release can markedly worsen the situation. There is strong evidence to suggest that women with ovarian Hyperstimulation (>20 follicles and blood estradiol levels that peak above 3,000pg/ml) who receive O.5mg of oral administration Cabergoline daily for 7 days, starting on the day of the hCG trigger, experience a significant reduction in the risk and severity of severe ovarian stimulation syndrome (OHSS). This is thought to be due to Cabergoline suppressing the production of vascular vasoactive substances such as VEGF that are produced by luteinized follicular granulosa cells, that increase the vascular permeability of local pelvic blood vessels.
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• ADDITIONAL INFORMATION:

  I am attaching online links to two E-books which I recently  co-authored with  my partner at SFS-NY  (Drew Tortoriello MD)……. for your reading pleasure:

  1.From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) “

  https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf

  1. “Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link

  https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view

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Repeat then hCG test in 2 days. It needs to double for confirmation.

Geoff Sher

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ADDITIONAL INFORMATION:

I am attaching online links to two E-books which I recently  co-authored with  my partner at SFS-NY  (Drew Tortoriello MD)……. for your reading pleasure:

1.From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) “

https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf

1. “Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link

https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view

………………………………………………………………..

I confess!, I have not been as active with posting blogs in recent months. However, I did pen 2 new ones on our website in the last month or so. I will try to do better going forward.

Geoff Sher

__________________________________________________________________

ADDITIONAL INFORMATION:

I am attaching online links to two E-books which I recently  co-authored with  my partner at SFS-NY  (Drew Tortoriello MD)……. for your reading pleasure:

1.From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) “

https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf

1. “Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link

https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view

………………………………………………………………..

No! It is not indicative that you cannot conceive with own eggs.

A hydatidiform molar pregnancy happens when tissue that normally forms the placenta instead becomes a growth, that triggers symptoms of pregnancy. A hydatidiform mole is a benign tumor of the root system (trophoblast) of the embryo which under normal conditions develops into the placenta which connects the baby to the mother. About 1 out of 2,000 women with early pregnancy symptoms will have a molar pregnancy. It is approximately twice as common in women of Asian extraction.The condition requires urgent treatment and follow-up to avoid serious complications that can involve invasion of the uterine wall and surrounding structures (i.e. invasive mole or chorioadenoma destruens) or malignant change (choriocarcinoma)

In more than 25% of early pregnancies there will be some vaginal bleeding. About one half of these end up by miscarrying. In the remaining half, the bleeding subsides and the pregnancy continues to evolve such that most will culminate in a healthy live birth. In less than 2% of cases of such bleeding the cause of early pregnancy bleeding is hydatidiform mole (molar) pregnancy. With molar pregnancy, the roots of the trophoblast (chorionic villi) undergo cystic degeneration and when the woman bleeds, these cystic structures are passed in dark blood, giving rise to the common description of “white currents floating in red currant jelly”.

In non-molar pregnancies, an inevitable miscarriage almost invariably presents with flattening or declining blood pregnancy hormone (i.e. hCG) levels. Conversely, with hydatidiform mole the blood hCG concentration is usually elevated continues to rise. In addition, the woman will often experience exaggerated pregnancy symptoms (e.g. pernicious vomiting, very frequent urination and bloating) and lower abdominal cramping. On examination, she will often be found to have a markedly elevated blood pressure. On abdominal or vaginal examination here uterus is commonly enlarged beyond that which can be explained on the basis of the duration of pregnancy. Ultrasound examination usually (but not invariably) reveals a hazy, so called “snow storm pattern” and the absence of a conceptus.

There are two types of hydatidiform mole, complete or partial

• Complete Hydatidiform mole:  Like normal pregnancies the complete mole has 46 chromosomes (two sets of 23), i.e. it is diploid.. However unlike with normal fertilization where one set of chromosomes comes from the mother and the other set from the father, with a complete molar pregnancy both sets of chromosomes come from the father. This is the result from duplication of a sperm’s chromosomes after it has fertilized an “inactive egg”. Since an embryo that has a YY karyotype is not viable, the chromosome gender of the molar pregnancy is invariably XX (female). Accordingly, if with IVF, one avoids transferring an embryo that by preimplantation genetic diagnosis (PGD) is found to be female (XX) and selectively transfers only male (XY) embryos the possibility of a complete molar pregnancy can be virtually eliminated. A complete molar pregnancy can result from fertilization of an “inactive egg” by 2 separate spermatozoa. Injection of a single sperm by ICSI avoids the latter from occurring altogether. In <10% of cases a complete Hydatidform molar pregnancy can be inherited due to a mutation (not yet clearly identified) involving chromosome 19. In such cases molar pregnancies can occur repetitively and the mole can have an XX or an XY chromosomal configuration. It should be borne in mind however, that not all repetitive molar pregnancies are due to this mutation. Complete molar pregnancies can also run in families (e.g. in  sisters). The true incidence of this genetic mutation is still unknown. This situation cannot be identified by PGD.

• Partial (placental) molar pregnancies are usually triploid [i.e. their cells contain three sets of (23each) chromosomes]. Thus with partial moles, the sex chromosome configuration will be XXY or XYY. Partial Hydatidform molar can therefore be avoided through selectively transferring embryos where through PGD triploidy has been excluded.

More than 80% of molar pregnancies are benign (noncancerous).  Treatment involves complete emptying of the uterus as soon as the diagnosis is made. Even in cases where a spontaneous passage of the molar tissue appears to be complete. The reason is to avoid the development of an invasive mole (chorioadenoma destruens), where the uterine wall is permeated by remaining tissue and to limit the development of choriocarcinoma (where the molar tissue becomes malignant). In the vast majority of properly managed cases however, outcome after treatment is usually excellent. Close follow-up with serial quantitative blood hCG testing, ultrasound and/or Magnetic Resonance Imaging (MRI) is essential. After treatment, the woman must use very effective contraception for at least 6 to 12 months so as to avoid pregnancy in order to allow for proper follow-up.

Choriocarcinoma is a very malignant tumor that invades the uterus and can spread rapidly via the blood system to bone, lungs, brain and other sites. Fortunately choriocarcinoma does respond well to hysterectomy and removal of ovaries with aggressive, selective chemotherapy.

While Molar pregnancy is not commonly seen in patients undergoing IVF, it does occur and the vigilant doctor should always be on the look-out for it. As indicated, in cases where a woman seeking IVF has a family history of the condition or has had a prior molar pregnancy herself, PGD can provide an efficient way to all but prevent this condition from occurring.

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ADDITIONAL INFORMATION:

I am attaching online links to two E-books which I recently  co-authored with  my partner at SFS-NY  (Drew Tortoriello MD)……. for your reading pleasure:

1.From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) “

https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf

1. “Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link

https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view

………………………………………………………………..

Don’t be too hard on yourself. These things happen. Besides it will likely in no way prejudice your cycle.

Good luck and G-d bless!

Geoff Sher

__________________________________________________________________

ADDITIONAL INFORMATION:

I am attaching online links to two E-books which I recently  co-authored with  my partner at SFS-NY  (Drew Tortoriello MD)……. for your reading pleasure:

1.From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) “

https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf

1. “Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link

https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view

………………………………………………………………..

Frequently, when following vigorous and often repeated flushing of follicles at egg retrieval they fail to yield eggs, it is ascribed to “Empty Follicle Syndrome.” This is a gross misnomer, because all follicles contain eggs. So why were no eggs retrieved from the follicles? Most likely it was because they would/could not yield the eggs they harbored.

This situation is most commonly seen in older women, women who have severely diminished ovarian reserve, and in women with polycystic ovarian syndrome (PCOS). In my opinion it is often preventable when an optimal, individualized and strategic protocol for controlled ovarian stimulation (COS) is employed and the correct timing and dosage is applied to the “hCG trigger shot.”

Normally, following optimal ovarian stimulation, the hCG “trigger shot” is given for the purpose of it triggering meiosis (reproductive division) that is intended to halve the number of chromosomes from 46 to 23 within 32-36 hours. The hCG trigger also enables the egg to signal the “cumulus cells” that bind it firmly to the inner wall of the follicle (through enzymatic activity), to loosen or disperse, so that the egg can detach and readily be captured at egg retrieval (ER).

Ordinarily, normal eggs (and even those with only one or two chromosomal irregularities) will readily detach and be captured with the very first attempt to empty a follicle. Eggs that have several chromosomal numerical abnormalities (i.e., are “complex aneuploid”) are often unable to facilitate this process. This explains why when the egg is complex aneuploid, its follicle will not yield an egg…and why, when it requires repeated flushing of a follicle to harvest an egg, it is highly suggestive of it being aneuploid and thus “incompetent” (i.e., incapable of subsequently propagating a normal embryo).

Older women, women with diminished ovarian reserve, and those with polycystic ovarian syndrome, tend to have more biologically active LH in circulation. LH causes production of male hormone (androgens, predominantly testosterone), by ovarian connective tissue (stroma/theca). A little testosterone is needed for optimal follicle development and for FSH-induced ovogenesis (egg development). Too much LH activity compromises the latter, and eggs so affected are far more likely to be aneuploid following meiosis.

Women with the above conditions have increased LH activity and are thus more likely to produce excessive ovarian testosterone. It follows that sustained, premature elevations in LH or premature luteinization (often referred to as a “premature LH surge”) will prejudice egg development. Such compromised eggs are much more likely to end up being complex aneuploid following the administration of the hCG trigger, leading to fruitless attempts at retrieval and the so called “empty follicle syndrome.”

The developing eggs of women who have increased LH activity (older women, women with diminished ovarian reserve, and those with PCOS) are inordinately vulnerable to the effects of protracted exposure to LH-induced ovarian testosterone. Because of this, the administration of medications that provoke further pituitary LH release (e.g., clomiphene and Letrozole), drugs that contain LH or hCG (e.g., Menopur), or protocols of ovarian stimulation that provoke increased exposure to the woman’s own pituitary LH (e.g., “flare-agonist protocols”) and the use of “late pituitary blockade” (antagonist) protocols can be prejudicial.

The importance of individualizing COS protocol selection, precision with regard to the dosage and type of hCG trigger used, and the timing of its administration in such cases cannot be overstated. The ideal dosage of urinary-derived hCG (hCG-u) such as Novarel, Pregnyl and Profasi is 10,000U. When recombinant DNA-derived hCG (hCG-r) such as Ovidrel is used, the optimal dosage is 500mcg. A lower dosage of hCG can, by compromising meiosis, increase the risk of egg aneuploidy, and thus of IVF outcome.

There is in my opinion no such condition as “Empty Follicle Syndrome.” All follicles contain eggs. Failure to access those eggs at ER can often be a result of the protocol used for controlled ovarian stimulation.

__________________________________________________________________________________________

ADDITIONAL INFORMATION:

I am attaching online links to two E-books which I recently  co-authored with  my partner at SFS-NY  (Drew Tortoriello MD)……. for your reading pleasure:

1.From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) “

https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf

1. “Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link

https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view

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