I would really need much more information to provide an authoritative opinion.

Feel free to call 702-533-2691 to set up an online consultation to discuss in depth.

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

………………………………………………………………..

In my opinion, it is possible, but highly unlikely that adenomyosis caused the missed abortion

I suggest that you contact my assistant, Patti Converse at 702-533-2691 and set up an online consultation with me to discuss..

Geoff Sher

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ADENOMYOSIS:

Adenomyosis is a condition where endometrial glands develop outside the uterine lining (endometrium), within the muscular wall of the uterus (myometrium). Definitive diagnosis of adenomyosis is difficult to make. The condition should be suspected when a premenopausal woman (usually>25 years of age) presents with pelvic pain, heavy painful periods, pain with deep penetration during intercourse, “unexplained infertility” or repeated miscarriages and thereupon, when on digital pelvic examination she is found to have an often smoothly enlarged (bulky) soft tender uterus. Previously, a definitive diagnosis was only possible after a woman had her uterus removed (hysterectomy) and it this was inspected under a microscope. However the use of uterine magnetic resonance imaging (MRI) now permits reliable diagnosis. Ultrasound examination of the uterus on the other hand , while not permitting definitive diagnosis, is a very helpful tool in raising a suspicion of the existence of adenomyosis.

Criteria used to make a diagnosis of adenomyosis on transvaginal ultrasound:

• Smooth generalized enlargement of the uterus.
• Asymmetrical thickening of one side of the (myometrium) as compared to another side.
• Thickening (>12mm) of the junctional zone between the endometrium and myometrium with increased blood flow.
• Absence of a clear line of demarcation between the endometrium and the myometrium
• Cysts in the myometrium
• One or more non discrete (not encapsulated) tumors (adenomyomas) in the myometrium.

 Since there is no proven independent relationship between adenomyosis and egg/embryo quality any associated reproductive dysfunction (infertility/miscarriages) might be attributable to an implantation dysfunction. It is tempting to postulate that this is brought about by adenomyosis-related anatomical pathology at the endometrial-myometrial junction. However, many women with adenomyosis, do go on to have children without difficulty. Given that 30%-70% of women who have adenomyosis also have endometriosis…. a known cause of infertility, it is my opinion that infertility caused by adenomyosis is likely linked to endometriosis where infertility is at least in part due to a toxic pelvic environment that compromises egg fertilization potential and/or due to an immunologic implantation dysfunction (IID) linked to activation of uterine natural killer cells (NKa). Thus, in my opinion all women who are suspected of having adenomyosis-related reproductive dysfunction (infertility/miscarriages) should be investigated for endometriosis and for IID. The latter, if confirmed would make them candidates for selective immunotherapy (using intralipid/steroid/heparin) in combination with IVF.

Surgery: Conservative surgery to address adenomyosis-related infertility involves excision of portions of the uterus with focal or nodular adenomyosis and/or excision of uterine adenomyomas. It is very challenging and difficult to perform because adenomyosis does not have distinct borders that distinguish normal uterine tissue from the lesions. In addition, surgical treatment for adenomyosis-related reproductive dysfunction is of questionable value and of course is  not an option for diffuse adenomyosis.

Medical treatment: There are three approaches.

• GnRH agonists (Buserelin/Lupron) which is thought to work by lowering estrogen levels.
• Aromatase inhibitors such as Letrozole have also been tried with limited success
• Inhibitors of angiogenesis: The junctional zone in women with adenomyosis may grow blood vessels more readily that other women (i.e. angiogenesis). A hormone known as VEGF can drive this process. It is against this background that it has been postulated that use of drugs that reduce the action of VEGF and thereby counter blood vessel proliferation in the uterus could have a therapeutic benefit. While worth trying in some cases, thus far such treatment has been rather disappointing
• Immunotherapy to counter IID: The use of therapies such as Intralipid (or IVIG)/steroids/heparin in combination with IVF might well hold promise in those women with adenomyosis who have NKa.

Fortunately, not all women with adenomyosis are infertile. For those who are, treatment presents a real problem. Even when IVF is used and the woman conceives, there is still a significant risk of miscarriage. Since the condition does not compromise egg/embryo quality, women with adenomyosis-related intractable reproductive dysfunction who fail to benefit from all options referred to above…(including IVF) might as a last resort consider  Gestational surrogacy.

Damage to the Fallopian tubes as a result of prior pelvic inflammation is one of the most common female causes of infertility. Commonly (as was the case with RL), this results blockage of the tubes at their ends, while leaving them open and  connected to the uterine cavity. In such cases the Fallopian tubes often progressively fill with fluid (hydrosalpinx), distending that contains dead cells and other noxious products….potentially toxic to embryos. Leakage of such fluid back wards into the uterus can severely compromise implantation of transferred embryos. This is why women with hydrosalpinges are strongly advised to have such diseased tubes removed or ligated (at the point that they emerge from the uterine wall), prior to undergoing embryo transfer. Admittedly, it is often hard for patients to accept that their tubes will be gone, as it means that future conception will require IVF. This is where it is necessary to be explain that  such tubes are functionless and that even if they could be rendered patent (opened) through surgery, the likelihood of pregnancy occurring would be remote.

Women with tubal occlusion who want to have a baby, will  invariably require IVF. In many such cases one or both of their tubes will, over time, have progressively filled with toxic fluid that can drain back into the uterine cavity and thwart post-ET implantation. It follows that all cases of tubal blockage be careful evaluated for hydrosalpinges before ET and that when detected,  this first  be  surgically addressed through tubal ligation or removal (salpingectomy).

Geoff Sher

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.
• _________________________________________________________
• 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

  ………………………………………………………………..

   

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

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

………………………………………………………………..

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

………………………………………………………………..