Ask Our Doctors – Archive
Our Medical Directors are outstanding physicians that you will find to be very personable and compassionate, who take care to ensure that you have the most cutting-edge fertility treatments at your disposal. This is your outlet to ask your questions to the doctors.
My prolactin is 30. Is this high enough to warrant medication to lower? I also have galactorrhea.
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.
Several other hypothalamic hormones, including thyroid releasing hormone (TSH) 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
Common manifestations of increased prolactin secretion (hyperprolactinemia) in women include amenorrhea (lack of menstrual cycles) and galactorrhea (excessive or spontaneous breast secretion of milk). Men with hyperprolactinemia may present with hypogonadism, decreased sex drive, perm dysfunction resulting in infertility and with impotence. Such men also often show breast enlargement (gynecomastia), but very rarely have galactorrhea.
Significantly raised blood prolactin levels (>60ng/ml) might point to a prolactin producing pituitary tumor (adenoma) which may be large (macroadenoma), small or even microscopic (microadenoma). Markedly elevated blood prolactin is also associated with other types of intracranial lesions such as craniopharyngiomas, meningiomas etc. Prolonged treatment with bromocryptine (Parlodel) will usually effectively lower blood concentrations and lead to shrinkage of the tumor. Such treatment is also safe during pregnancy. Other intracranial lesions causing hyperprolactinemia are usually treated by surgical removal.
Certain drugs: (e.g. tranquilizers, ganglion blocker antihypertensives, antidepressants, thiazides and narcotics) can also lead to significant elevations in prolactin. 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.
Elevated Prolactin and Reproductive Performance: It is important to recognize that even modestly raised prolactin levels (20ng/ml-40ng/ml) can interfere with endometrial proliferation as well as ovarian follicle growth and development, thereby reducing the likelihood of successful implantation, and may require treatment with prolactin suppressants such as bromocryptine (Parlodel). A modest elevation in blood prolactin can also point to an underlying state of hypothyroidism which (as explained elsewhere) in women is usually autoimmune in origin and be associated with increased uterine natural killer cell activity (NKa). The latter may profoundly impair implantation leading to “perceived infertility” or recurrent pregnancy loss.
It is important to note that ATA with NKa can be present prior to the development of clinically overt autoimmune hypothyroidism (Hashimoto’s disease). Since such women will often present with an unexplained elevation in blood TSH and/or prolactin levels, it is wise to always test for the presence of antithyroid antibodies (ATA) such as antithyroglobulin and antimicrosomal antibodies. If the ATA level is elevated, a NKa test (K-562 target cell test) should also be done because in 50% of such cases, there will often also be associated reproductive failure that manifests as “unexplained infertility, unexplained (often repeated) IVF failure or recurrent pregnancy loss (RPL)…due to immunologic implantation dysfunction.
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 8th week of pregnancy and then tailed off over 2 weeks.
If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .
*FYI
The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Can adenomyosis cause early miscarriage?
Only if it is associated with a thin uterine lining.
Geoff Sher
Hi Dr Sher,
I underwent donor egg IVF in May 2017 and I was pregnant until 7th week and miscarried. Since this was my 2nd consecutive miscarriage, my partner and I went through chromosome testing, I also went through immunology testing such as killer cell etc (about 25 different tests) and the results only showed that I have one copy of MTHFR gene mutation (C667). I was told that I would need to take methylfolate supplements to fix that. They didn’t find anything else wrong chromosomally.
I would like to try again using the embryos I have leftover. I was wondering if I need additional immunologic protocol before and after the transfer. I read and watched all of your videos/articles on RPL and immunology.
Thank you very much for your advice.
I doubt the thrombophilia (MTHFR mutation) explains your recurrent losses or that treatment of van MTHFR mutation will be therapeutically impactful. In addition, you might well not have done the correct immune tests or have done the testing correctly. There are only approximately 4 Reproductive Immunology Reference Laboratories in the USA that can do the required testing adequately.
Unless tests for immunologic implantation dysfunction (IID) are performed correctly and conducted by a one of the few reliable reproductive immunology reference laboratory in the United States, treatment will likely be unsuccessful. . In this regard it is most important that the right tests be ordered and that these be performed by a competent laboratory. There are in my opinion only a handful of reliable Reproductive Immunology Laboratories in the world and most are in the U.S.A. Also, it is my opinion that far too often, testing is inappropriate with the many redundant and incorrect tests being requested from and conducted by suboptimal laboratories. Finally for treatment to have the best chance of being successful, it is vital that the underlying type of IID (autoimmune IID versus alloimmune) be identified correctly and that the type, dosage, concentration and timing of treatments be carefully devised and implemented.
Who Should Undergo IID testing?
When it comes to who should be evaluated, the following conditions should in always raise a suspicion of an underlying IID, and trigger prompt testing:
•A diagnosis of endometriosis or the existence of symptoms suggestive of endometriosis (heavy/painful menstruation and pain with ovulation or with deep penetration during intercourse) I would however emphasize that a definitive diagnosis of endometriosis requires visualization of the lesions at laparoscopy or laparotomy)
•A personal or family history of autoimmune disease such as hyper/hypothyroidism (as those with elevated or depressed TSH blood levels, regardless of thyroid hormonal dysfunction), Lupus erythematosus, Rheumatoid arthritis, dermatomyositis, scleroderma etc.)
•“Unexplained” infertility
•Recurrent pregnancy loss (RPL)
•A history of having miscarried a conceptus that, upon testing of products of conception, was found to have a normal numerical chromosomal configuration (euploid).
•Unexplained IVF failure
• “Unexplained” intrauterine growth retardation due to placental insufficiency or late pregnancy loss of a chromosomally normal baby
What Parameters should be tested?
In my opinion, too many Reproductive Immunologists unnecessarily unload a barrage of costly IID tests on unsuspecting patients. In most cases the initial test should be for NK cell activation, and only if this is positive, is it necessary to expand the testing.
The parameters that require measurement include:
oFor Autoimmune Implantation Dysfunction: Autoimmune implantation dysfunction, most commonly presents with presumed “infertility” due to such early pregnancy losses that the woman did not even know she was pregnant in the first place. Sometimes there as an early miscarriage. Tests required are: a) blood levels of all IgA, IgG and IgM-related antiphospholipid antibodies (APA’s) directed against six or seven specific phospholipids, b) both antithyroid antibodies (antithyroid and antimicrosomal antibodies), c) a comprehensive reproductive immunophenotype (RIP) and, c) most importantly, assessment of Natural Killer (NK) cell activity (rather than concentration) by measuring by their killing, using the K-562 target cell test and/or uterine cytokine measurement. As far as the ideal environment for performing such tests, it is important to recognize that currently there are only about 5 or 6, Reproductive Immunology Reference Laboratories in the U.S capable of reliably analyzing the required elements with a sufficient degree of sensitivity and specificity (in my opinion).
oFor Alloimmune implantation Dysfunction: While alloimmune Implantation usually presents with a history of unexplained (usually repeated) miscarriages or secondary infertility (where the woman conceived initially and thereupon was either unable to conceive started having repeated miscarriages it can also present as “presumed” primary infertility. Alloimmune dysfunction is diagnosed by testing the blood of both the male and female partners for matching DQ alpha genes and NK/CTL activation. It is important to note that any DQ alpha match (partial or complete) will only result in IID when there is concomitant NK/CTL activation (see elsewhere on this blog).
How should results be interpreted?
Central to making a diagnosis of an immunologic implantation dysfunction is the appropriate interpretation of natural killer cell activity (NKa) .In this regard, one of the commonest and most serious errors, is to regard the blood concentration of natural killer cells as being significant. Rather it is the activity (toxicity) of NK cells that matters as mentioned. Then there is the interpretation of reported results. The most important consideration is the percentage of target cells “killed” in the “native state”. In most cases a level of >10% killing should be regarded with suspicion and >12% overtly abnormal. In my opinion, trying to interpret the effect of adding IVIG or Intralipid to the sample in order assess whether and to what degree the use of these products would have a therapeutic benefit is seriously flawed and of little benefit. Clinically relevant NK cell deactivation can only be significantly effected in vivo and takes more than a week following infusion to occur. Thus what happens in the laboratory by adding these products to the sample prior to K-562 target cell testing is in my opinion likely irrelevant.
There exists a pervasive but blatant misconception on the part of many, that the addition of Intralipid (IL) /immunoglobulin-G IVIG) can have an immediate down-regulatory effect on NK cell activity. This has established a demand that Reproductive Immunology Reference Laboratories report on NK cell activity before and following exposure to IVIG and/or IL. However, the fact is that activated “functional” NK cells (NKa) cannot be deactivated in the laboratory. Effective down-regulation of activated NK cells can only be adequately accomplished if their activated “progenitor/parental” NK cells are first down-regulated. Thereupon once these down-regulated “precursor” NK cells are exposed to progesterone, they will begin spawning normal and functional NK cells, which takes about 10-14 days. It follows that to assess for a therapeutic response to IVIG/IL therapy would require that the patient first be treated (10-14 days prior to embryo transfer) and thereupon, about 2 weeks later, be retested. While at 1st glance this might seem to be a reasonable approach, in reality it would be of little clinical benefit because even if blood were to be drawn 10 -14 days after IL/IVIG treatment it would require an additional 10 days to receive results from the laboratory, by which time it would be far too late to be of practical advantage.
Neither IVIG nor IL is capable of significantly suppressing already activated “functional NK cells”. For this to happen, the IL/IVIG would have to down-regulate progenitor (parent) NK cell” activity. Thus, it should be infused 10-14 several prior to ovulation or progesterone administration so that the down-regulated “progenitor/precursor” NK cells” can propagate a sufficient number of normally regulated “functional NK cell” to be present at the implantation site 7 days later. In addition, to be effective, IL/IVIG therapy needs to be combined with steroid (dexamethasone/prednisone/prednisolone) therapy to down-regulates (often) concomitantly activated T-cells.
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
•The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
•The Fundamental Requirements for Achieving Optimal IVF Success
•Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
•The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
•Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
•Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
•Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
•Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
•Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
•Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
•Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .
*FYI
The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoffrey Sher MD
I am 31 y.o. with “normal labs” and am questioning the protocol from my ER that only retrieved 5 mature eggs. I have AMH 1.27, FSH was “low end of normal” (I can’t recall the exact number) and had 14 follicles on day 3. On day 5 I started 225 units follistim/1 vial menopur, (day 1 of treatment) which dropped to 150 follistim/1 vial menopur on day 4 of treatment. On day 4 I also added 250 mcg ganirelix. I was stimmed 9 days, and on day 10 triggered with hcg and 0.2 ml Lupron, with an additional 0.2 ml Lupron 12 hrs later. Retrieval on day 12 produced 9 eggs, only 5 of which were mature. I was expecting 10-12 based on my original follicle count of 14 (which went up to 19 during stim). What went wrong?
Hi mariane.
You do have slightly diminished ovarian reserve (DOR). I do not advocate late Ganirelix suppression in such cases. I also do not favor Lupron for the trigger. This approach is only indicated when there is concern regarding hyperstimulation and that does not apply in your case…given your DOR.
In my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting embryo “competency”.
Women who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which in turn can have a deleterious effect on egg/embryo “competency”.
While it is presently not possible by any means, to reverse the effect of DOR, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can in my opinion, make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.I try to avoid using such protocols/regimes (especially) in women with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which by allowing them to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly enhance the opportunity to achieve a viable pregnancy
Please visit my new Blog on this very site, https://www.drgeoffreysherivf.com, find the “search bar” and type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
• The Fundamental Requirements For Achieving Optimal IVF Success
• Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers should be the Standard of Care in IVF
• Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
• Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation.
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally Abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• Traveling for IVF from Out of State/Country–
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF.
• The Role of Nutritional Supplements in Preparing for IVF
• Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
• IVF Egg Donation: A Comprehensive Overview
If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .
*FYI
The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoffrey Sher MD
hi dr sher,
i was pregnant thru ivf. we transferred two frozen embryos. 4 weeks hcg 220, four days later 1020hcg. they were concern at the time because it was so high. i checked and it was in the twins bracket. but at 5 weeks they found sac and then heart beat. i was released to my obgyn. they also found a small hematoma around the embryo. in the beginning of 1st trimester all was fine. then i started spotting everyday for 2-3 weeks. the hospital also found the small hematoma near the baby. on my 1st trimester screening, they found a thick NT 3.0-3.5 and then 3.7 a few days later. i took the nipt verifi and the results came back 95% positive screening for down syndrome. they also saw his nasel bone. i just had my amnio yesterday and waiting for fish results. i’m so worried. they also check the baby again yesterday, the thick NT went away and found no other markers for chromosome abnormalities. baby has his liver, kidney, brain, and even all his toes. do you know it is possible that the failed embryo was absorbed by myself or current baby’s placenta and is what’s causing the abnormal dna found in my blood during nipt? you mentioned many moms with ivf pregnancy where multiple embryos are transferred don’t even know they had vanishing twins/embryos because it occurs during early stages before ultra sound is done. i also read online that vanishing twin is one of the causes of false positive in nipt testing. since the blood test for baby dna. i read during sperm stages, sperms have dna. embryos have dna as well. i had two failed ivf cycles before this pregnancy. could all of the failed embryos from past cycles plus the recent failed embryo from this cycle be circulating in my blood? i haven’t slept well for over two weeks because i had to wait till i’m 16 weeks for amnio. i’m just praying you can tell me that my baby has a chance to be a normal baby. i also had a carrier testing done and it came back negative. not sure if that will help my baby’s chances. pls advise. thank you so much
I would not be panicked at this stage. All could still be well. The amnio result would be definitive though. My bet is you will be OK.
Please keep me informed!
Good luck and G-d bless!
Geoff Sher