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.
I am wondering whether an active pelvic infection and ovarian abscess (mistaken for ovarian cysts) would result in a poor IVF outcome? Would having a surgery to remove all adhesions and remove the inflammed tissue possibly yield better IVF outcome?
If there was active pelvic infection, then sure”’ it would in my opinion have compromised response and outcome. But if the inflammation is gone and there is no longer an abcess , then the adhesions alone should not adversely affect the process. I suggest you have this assessed and your ovarian reserve re-tested before entering another cycle.
Perhaps we should talk!
Pelvic inflammatory disease (PID) is a condition where inflammation occurs of pelvic structures as a result of: sexual transmission via the vagina and cervix; contamination from other inflamed structures in the abdominal cavity) appendix, gallbladder, kidneys, etc.); a foreign body inside the uterus (i.e., the intrauterine device – IUD); contamination of retained products of conception following abortion or child birth; and rarely as a result of blood-born bacterial transmission (e.g., pelvic tuberculosis which is common in developing countries but rare in the United States.
It is estimated that about 1,500,000 women develop PID annually in the United States and the number is growing. Less than one-third of these women present with symptoms or signs of acute inflammation (e.g. severe pain, malaise, fever, vaginal discharge). The remaining cases usually go undetected until the woman presents with symptoms or infertility. In fact, more that 60% of patients who undergo surgery or in vitro fertilization and embryo transfer (IVF/ET) for the treatment of infertility secondary to pelvic inflammatory disease, provide no history of a prior acute episode.
Acute PID: Where pelvic inflammatory disease presents as an acute illness with fever, sever lower abdominal pain, accompanied by a yellow or blood stained, nonirritant, vaginal discharge and vomiting which usually prompts the woman to seek urgent medical attention.
Subacute PID: Here, the onset of PID is gradual, less severe, and often goes unnoticed until superimposed acute PID occurs, or chronic incapacitating symptoms prompt the woman to seek medical attention (see below).
Chronic Pelvic Inflammatory Disease: Chronic PID is a consequence of untreated or unsuccessfully managed acute and/or subacute PID. The woman usually presents with symptoms of pelvic pain, heavy and painful menstrual periods, pain with intercourse (dyspareunia) and infertility.
In the vast majority of cases, PID results from the sexual transmission of infecting organisms such as Neisseria Gonorrhea, and Chlamydia Trachomatis, which are readily eradicated through appropriate antibiotic therapy. Sexually transmitted bacteria first infect the cervix (the opening into the uterus) through which is ascends via the uterus to the fallopian tubes, ovaries, and other pelvic structures.
There are several important factors which predispose women towards developing PID:
1.Exposure to an infected partner;
2.Exposure blood provides and excellent growth medium for bacteria, promoting their proliferation and passage into the fallopian tubes;
3.Relative ill health and poor nutritional status. It is predominantly for this reason that PID is much more prevalent in lower socioeconomic groups;
4.The fact that previously infected tissues are highly susceptible to re-infection; resulting in women with a past history of PID being highly susceptible to recurrent attacks.
While sexually transmitted PID is certainly capable of causing endometritis (inflammation of the uterine lining) the uterus itself is not the main focus of the inflammatory process. Cyclical shedding of most of the uterine lining with menstruation tends to remove infected tissue monthly, thereby preventing the inflammation from taking a hold and causing permanent damage to or scarring of the uterine lining (the endometrium). The main site/target of inflammation following sexual transmitted PID is the fallopian tube via which other pelvic and abdominal structures may be infected.
PID following pregnancy (childbirth or abortion): This primarily targets the uterine lining, causing endometritis. Organisms such as Bacteroides, Peptostreptococcus, Beta hemolytic streptococcus, and E.Coli readily proliferate in the products of conception that are sometimes retained in the uterus following childbirth and abortion. The delayed onset of menstruation after both childbirth and abortion provides an opportunity for the inflammatory process to take hold and progress, sometimes leading to the development of scar tissue in the uterine cavity with the opposing surfaces of the endometrium to fuse together or produce scarring (Asherman syndrome). Sometimes the inflamed endometrium obliterates the opening (in the uterus) into the fallopian tubes and might also damage a small, adjacent segment of the tubes. Less commonly, post-childbirth and post-abortal endometritis infects the entire fallopian tube(s) (salpingitis) as well as causing partial or complete blockage, and/or spreading into the pelvic cavity.
PID from the use of the intrauterine contraceptive device (IUD) for contraceptive purposes: This most commonly occurs in cases where the device is inserted into the uterus of women concurrently infected with Gonorrhea or Chlamydia. The IUD acts as a foreign body causing local irritation which compromises the normal defense mechanisms that normally protect against infection. At the same time, the IUD string which protrudes through the cervix into the vagina may act as a “wick” via which infecting organisms gain entrance to the uterus. As with post-abortal and post-childbirth endometritis, IUD-related uterine infection can cause scarring of the endometrial lining, blockage of the fallopian tubes where they leave the uterus (utero-cornual occlusion, and spread, via the tubes, to other pelvic structures. IUD-related PID is a potentially life endangering condition capable of causing pelvic abscess formation, the development of peritonitis (inflammation of the peritoneum), systemic infection (septicemia), and shock.
How PID Causes Tubal Infertility: Sexually transmitted PID caused by Gonorrhea or Chlamydia rapidly spreads via the cervix and uterus to the fallopian tube(s). These organs are highly specialized and are designed to promote the active passage of eggs, sperm, and embryos in a timely manner to and from the uterine cavity. They contain cells whose function is to protect and nurture eggs, sperm and embryos in transit. At their ends, the fallopian tubes have small delicate finger-like projections (fimbriae) that approximate, envelope, and “pick-up” the egg(s) from the ovary(s) at the time of ovulation. Inflammation due to Chlamydia Trachomatis and Neiserria Gonorrhea, damages and often permanently destroys the specialized lining of the fallopian tube(s) and in severe cases results in fusion of the fimbriae thereby clocking the ends of the tube(s) compromising their mobility and their potential to facilitate timely passage of eggs, sperm and embryos. Pus which accumulated inside the tube(s) often passes into the pelvic cavity producing peritonitis and results in the formation of scar tissue (adhesions) which further disrupts normal pelvic anatomy as well as the relationship between the tube(s) and the ovary(ies). This may prevent the fallopian tubes from collecting the egg(s) during ovulation.
As previously stated, post-abortal and post-childbirth endometritis causes infertility by causing uterine scarring, occlusion of the fallopian tube at its junction with the uterus, and sometimes producing infection along the full length of the tube with resultant tubal damage.
Sexually transmitted PID: This almost invariably affects both fallopian tubes. Even in cases where a dye x-ray test (hysterosalpingogram) or laparoscopy (a procedure where a telescope-like instrument is passed through the belly button to visualize the pelvic structures) indicates that only one fallopian tube has been infected, the other tube is almost invariably involved. A new procedure called tuboscopy (where a thin fiberoptic telescope is passed into the fallopian tube(s) to evaluate the inner structure) has confirmed that the tubes of PID victims, who seemingly have normal pelvic anatomy, oftentimes have internal scarring and/or adhesion. This could account for the low success rate seen with tubal reparative surgeries and the high ectopic pregnancy rate (8-15%) in PID patients who subsequently conceive.
Ureaplasma Urealyticum Infection: Ureaplasma urealyticum infection is an organism which causes a relatively benign form of PID. Often times neither partner has any symptoms or signs of the condition. It has been implicated as a possible cause of both infertility and early recurrent miscarriages. The organism is sexually transmitted and infects the lining of the cervical canal. It rarely produces symptoms of severe physical complications in its female victims. In men, it sometimes causes nonspecific urethritis and/or prostatitis, but in the majority of cases is asymptomatic. Recent research suggests that infection with Ureaplasma urealyticum might be capable of altering the physico-chemical properties of cervical mucus and/or cervical secretions, so that when a catheter is passed into the uterus to transfer embryos or sperm, the organisms gait entry to the uterine cavity, and produce and environment that is inhospitable to embryos.
Management: Emphases should be placed on the prevention of PID by appropriate population screening for sexually transmitted diseases and through the promotion of condom usage in non-monogamous sexual relationships. Acute PID should be vigorously treated with the appropriate antibiotics. Gonorrhea is usually successfully treated with penicillin derivatives, cephalosporins, erythromycin, ciprofloxin and tetracyclines. Anaerobic organisms such as Bacteroides and Peptostreptococcus are responsive to metronidazole (Flagyl), ciprofloxin and in some cases to doxycycline. Beta hemolytic Streptococcus and E. coli respond to penicillin derivatives, tetracyclines, and cephalosporins and ciprofloxin. E. coli can also be treated with the gentamicin. PID due to Chlamydial infection responds well to doxycycline, erythromycin, and ciprofloxin therapy, but will usually not respond to penicillin derivatives or cephalosporins. Ureaplasma urealyticum infections likewise respond well to the same antibiotics and to Flagyl.
All active sexual contacts should be treated concurrently and follow up cultures should always be performed to confirm complete eradication of the disease.
The pain, heavy bleeding, and debilitation associated with chronic PID often necessitates removal of the tube(s) and sometimes even hysterectomy, especially in women who have no childbearing aspirations. Younger women who are desirous of having a child might defer such treatment while enduring ongoing symptoms, in the hope of conceiving in the interim.
Diagnosing Tubal damage due to PID: Tubal blockage can occur anywhere in the fallopian tubes. It sometimes occurs in the part of the Fallopian tube that passes through the wall of the uterus. It can also occur in the mid-section of the tube. Most commonly however, it occludes the far end of the tubes.
A hysterosalpingogram (HSG) is the most widely used screening test for damaged or blocked tubes. It involves the injection of a radio-opaque dye through the cervix into the uterus. Successive x-rays are then taken in rapid succession to track passage of the dye into the uterus and then to determine whether it passes into the Fallopian tubes and then spills into the pelvic cavity. However, a HSG showing patent tubes, cannot usually diagnose tubal damage. All it tells you is whether the petal-like fimbriated ends of the tubes have not fused and blocking their ends. It is especially important to take bear this fact in mind whenever the tubes are found to be open, in spite of there being a history of prior PID. A diagnostic laparoscopy is much more reliable for diagnosing both tubal blockage and damage.
Treating Tubal Damage due to PID: Tubal damage is one of the commonest causes of infertility. The Fallopian tubes are not merely “pipes”; they are highly complex structures that pick up the ovulated egg and help move it towards the uterus. Normal fertilization occurs in the tube. And, as stated above, damage to Fallopian tubes is most often caused by PID.
During the 1980’s, surgery was regarded as the mainstay of treatment for infertility secondary to PID. The advent of high success rates with in vitro fertilization as performed in selected centers of excellence has changed all of that. Today, virtually without exception, most fertility specialists would agree that IVF is the treatment of choice for almost all forms of tubal infertility.
Surgery to unblock fallopian tubes or clear adhesions resulting from an inflammatory process due to infections with gonorrhea or Chlamydia is truly an exercise in futility. The chances of pregnancy occurring following such an undertaking is less than 2% per month, and less than 25% in three years.
Then there is the fact that there is a high incidence of ectopic pregnancy following tubal surgery (15-20%) and this can be a life endangering condition. Finally, more than 70% of patients undertaking such an escapade would ultimately need IVF anyway, there is no longer any medical justification to choose tubal surgery over IVF.
Hydrosalpinx: In cases where the ends of the fallopian tubes are blocked, pus may collect and distend the tube(s). The pus is usually absorbed over time and replaced by clear straw-colored fluid. The resulting, occluded, fluid-filled, distended, and often functionless fallopian tube(s) is referred to as a hydrosalpinx.. Such distended Fallopian tubes (hydrosalpinges) can leak fluid back into the uterine cavity where the can destroy transferred embryos upon contact. This is why patients who have hydrosalpinges and are considering undergoing IVF, should first have hydrosalpinges surgically removed or at the very least have the affected tube(s) surgically clipped or tied as they emerge through the uterine wall. This will avoid subsequent back flow when IVF is performed. Understandably, it is often hard for patients to come to terms with the fact that following such surgery they no longer have any possibility of having functional Fallopian Tubes. Such women should be counseled that hydrosalpinges are functionless tubes anyway and that any attempt to open such tubes surgically in an attempt to restore fertility would be an exercise in futility, anyway.
In a nutshell: Tubal surgery is a very poor alternative to IVF. Infertility associated with tubal blockage, especially if due to PID, is an absolute indication for IVF. I would go even further in stating that any tubal damage due to PID, whether or not it is associated with blockage is an indication for IVF.
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ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.
Patients are encouraged to share the information I provide, with their treating Physicians and/or to avail themselves of my personal hands-on services, provided through batched IVF cycles that I conduct every 3 months at Los Angeles IVF (LAIVF) Clinic, Century City, Los Angeles, CA.
If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).
PLEASE SPREAD THE WORD ABOUT SFS!
Geoff Sher
Hi Dr. Sher,
I recently underwent my first fresh embryo transfer following my second egg retrieval. I have PCOS. First retrieval I had 14 eggs retrieved, with 1 egg mature on day 1. The embryo from this retrieval made it to day 3 at 6 cells and was frozen. In between the first and second retrieval I was put on Metformin 100 mg per day and Ovasitol daily. I did keto diet and lost 20 lbs. However it appears this did not affect my androgens. I know I have adrenal PCOS so maybe there is only so much sugar metabolism has to do with it. I did not get better quality eggs after following this advice. Second transfer yielded 16 eggs; none mature on day 1. By day 2 late ICSI gave one 4 cell embryo. We transferred this embryo on day 2; I did not get pregnant.
I want to know why I produced so many immature eggs and only one mature egg? Also why did my fresh transfer fail; before I transfer the frozen embryo is there anything I should do? I am considering ERA before the transfer. My husband is wary of doing any more retrievals since the first two were not so great. We are considering donor eggs as well since it appears my eggs are poor quality. My husband is fertile and his sperm are wonderful. Is there anything I should consider doing before going to donor eggs? I really want to have my own child but do not want to risk my health. I had some fluid outside my ovaries during the second retrieval. They aspirated this during retrieval. I was put on Dostinex for 8 days to help with fluid buildup. I did not develop OHSS but it was not pleasant.
Thanks,
Katie Foster
In my opinion, if you have adrenal PCOS, you would need:
a. Steroid therapy for 4-6 weeks before starting the cycle and confirm that your DHEAS and 17 hydroxy-progesterone have returned to baseline before stimulating for the cycle.
b) That the protocol used for ovarian stimulation is individualized and customized for your needs.
The importance of the IVF stimulation protocol on egg/embryo quality cannot be overstated. This factor seems often to be overlooked or discounted by t IVF practitioners who use a “one-size-fits-all” approach to ovarian stimulation. My experience is that the use of individualized/customized COS protocols can greatly improve IVF outcome. While no one can influence underlying genetics or turn back the clock on a woman’s age, any competent IVF specialist should be able to tailor the protocol for COS to meet the individual needs of the patient.
Gonadotropins (LH and FSH), whether produced by the pituitary gland or administered by way of fertility drugs, have different “targeted” sites of action in the ovary. FSH targets cells that line the inner wall of the follicle (granulosa cells) and also form the cumulus cells that bind the egg to the inner surface of the follicle. Granulosa cells are responsible for estrogen production.
LH, on the other hand, targets the ovarian connective tissue (stroma/theca) that surrounds ovarian follicles resulting in the production of male hormones such as testosterone (predominantly), androstenedione and DHEA. These androgens are then transported to the granulosa cells of the adjacent follicles in a “bucket brigade fashion”. There FSH converts testosterone to estradiol, causing granulosa cells to multiply (proliferate) and produce estradiol, follicles to grows and eggs to develop (ovogenesis) It follows that ovarian androgens (mainly testosterone) is absolutely indispensable to follicle/ egg growth and development.
However, the emphasis is on a “small” amount of testosterone. Over-exposure of the follicle to testosterone can compromise egg development and lead to an increased likelihood of chromosomal irregularities (aneuploid) following LH/hCG-induced egg maturational division (meiosis) and compromise embryo “competency/quality.
Ovarian androgens can also reach the uterine lining where they sometimes will compromise estrogen receptor -induced endometrial growth and development.
Many older women and those who have diminished ovarian reserve (DOR) have increased LH activity is increased. Such women either over-produce LH and/or the LH produced is far more biologically active. Chronically increased LH activity leads to overgrowth of ovarian connective tissue (stroma/theca). This condition, which is often referred to as Stromal Hyperplasia or hyperthecosis can result in excessive ovarian androgen/testosterone production and poorer egg-embryo quality/competency, Similarly, women with polycystic ovarian syndrome (PCOS), also characteristically have Stromal hyperplasia/hyperthecosis due to chronically increased LH activity. Thus they too often manifest with increased ovarian androgen production. It is therefore not surprising that “poor egg/embryo quality” is often also a feature of PCOS.
In my opinion, the over-administration of LH-containing menotropins such as Menopur, [which is comprised of roughly equal amount of FSH and hCG ,which acts similar to LH)], to older women, women with DOR and those who have PCOS can also lead to reduced egg/embryo competency . Similarly, drugs such as clomiphene or Letrozole that cause the pituitary gland to release excessive amounts of LH, are also potentially harmful to egg development and in my opinion, are best omitted from IVF COS protocols. This is especially the case when it comes to older women and those with DOR, who in my opinion should preferably be stimulated using FSH-dominant products such as Follistim, Puregon, Fostimon and Gonal-F.
Gonadotropin releasing hormone agonists (GnRHa): GnRHa such as Lupron, Buserelin, Superfact, Gonopeptyl etc. are often used to launch ovarian stimulation cycles. They act by causing an initial outpouring followed by a depletion of pituitary gonadotropins. This results in LH levels falling to low concentrations, within 4-7 days, thereby establishing a relatively “LH-free environment”. When GnRHa are administered for about 7 days prior to initiating gonadotropin stimulation (“long” pituitary down-regulation”), the LH depletion that will exist when COS is initiated, will usually be protective of subsequent egg development. In contrast, when the GnRHa administration commences along with the initiation of gonadotropin therapy, there will be a resultant immediate surge in the release of pituitary LH with the potential to increase ovarian testosterone to egg-compromising levels , from the outset of COS. This, in my opinion could be particularly harmful when undertaken in older women and those who have DOR.
GnRH-antagonists such as Ganirelix, Cetrotide and Orgalutron, on the other hand, act very rapidly (within hours) to block pituitary LH release. The purpose in using GnRH antagonists is to prevent the release of LH during COS. In contrast, the LH-lowering effect of GnRH agonists develops over a number of days.
GnRH antagonists are traditionally given, starting after 5th -7th day of gonadotropin stimulation. However, when this is done in older women and those (regardless of age) who have DOR, LH-suppression might be reached too late to prevent the deleterious effect of excessive ovarian androgen production on egg development in the early stage of ovarian stimulation. This is why, it is my preference to administer GnRH-antagonists, starting at the initiation of gonadotropin administration.
My preferred Protocols for Controlled Ovarian Stimulation (COS):
1.“Long” GnRHa (Lupron/Buserelin/Superfact/Gonopeptyl) Pituitary Down-regulation Protocol: The most commonly prescribed protocol for GnRHa/gonadotropin administration is the so-called “long protocol”. Here, GnRHa is given, starting a week or so prior to menstruation. This results in an initial rise in FSH and LH , which is rapidly followed by a precipitous fall to near zero. It is followed by a withdrawal bleed (menstruation), whereupon gonadotropin treatment should commence, while daily Lupron injections continue, to ensure a “low LH” environment. A modification to the “long protocol” which I prefer prescribing for older women and in cases of DOR, is the Agonist/Antagonist Conversion Protocol (A/ACP) where, upon the onset of a GnRHa-induced bleed, the agonist is supplanted by an antagonist (Ganirelix/Cetrotide/Orgalutron) and this is continued until the hCG trigger. In many such cases I often supplement with human growth hormone (HGH) in such cases in an attempt to enhance egg mitochondrial activity and so enhance egg development. This approach is often augmented with preimplantation genetic screening (PGS) of all embryos that reach the expanded blastocyst stage of development by day 5-6 post-fertilization. I also commonly recommend blastocyst banking to many such patients.
2.
3.Short (“Flare”) GnRHa Protocol: Another GnRHa usage for COS is the so called “(micro) flare protocol”. This involves initiating gonadotropin therapy commensurate with initiation of gonadotropin administration. The supposed objective is to deliberately allow Lupron to elicit an initial surge (“flare”) in pituitary FSH release in order to augment FSH administration by increased FSH production. Unfortunately, this “spring board effect” constitutes “a double-edged sword”. While it indeed increases the release of FSH, it at the same time causes a surge in LH release. The latter can evoke excessive ovarian stromal/thecal androgen production which could potentially compromise egg quality, especially when it comes to older women and women with DOR. I am of the opinion that by evoking an exaggerated ovarian androgen response, such “(micro) flare protocols” can harm egg/embryo quality and reduce IVF success rates, especially when it comes to COS in older women, and in women with diminished ovarian reserve. Accordingly, I do not prescribe such protocols to my IVF patients.
4.Estrogen Priming – This is the approach I sometimes prescribe for my patients who have virtually depleted ovarian reserve , as determined by very low blood anti-Mullerian hormone AMH levels (<0.2ng/ml or 2 pmol/L) and are thus likely to be very “poor responders”. It involves a modified A/ACP. We start with the birth control pill (BCP) for 10 days or longer, overlap it for 3 days with a GnRHa whereupon the BCP is stopped. Th GnRHa is continued until the onset of menstruation (usually 5-7 days later) to cause pituitary LH, down-regulation. Upon menstruation and confirmation by ultrasound and measurement of blood estradiol levels that adequate ovarian suppression has been achieved, the dosage of GnRHa is stopped and is immediately supplanted by daily administration of GnRH antagonist. The patient is given twice-weekly injections of estradiol valerate (Delestrogen) for a period of 8 days whereupon COS is initiated using a relatively high dosage FSH-(Follistim, Fostimon, Puregon or Gonal F), which is continued along with daily administration of GnRH antagonist until the “hCG “trigger.” This approach is often augmented with HGH administration throughout the process of COS and by preimplantation genetic screening (PGS) of all embryos that reach the expanded blastocyst stage of development by day 5-6 post-fertilization. I also commonly recommend blastocyst banking to many such patients.
Estrogen Priming has succeeded in significantly enhancing ovarian response to gonadotropins in many of otherwise very poor responders.
Triggering egg Maturation prior to egg Retrieval: hCG versus GnRHa
With ovulation induction using fertility drugs, the administration of 10,000U hCGu (Pregnyl; Profasi, Novarel) or 500mcg hCGr (Ovidrel/Ovitrel) “trigger”) sends the eggs (into maturational division (meiosis). This process is designed to halve the chromosome number, resulting in mature eggs (M2) that will have 23 chromosomes rather that the 46 chromosomes they had prior to the “trigger”. Such a chromosomally numerically normal (euploid), mature (MII) eggs, upon being fertilized will (hopefully) propagate euploid embryos that have 46 chromosomes and will be “: competent” to propagate viable pregnancies. In my opinion, the key is to always “trigger” with no less than 10,000U of hCGu or 500mcg hCGr (Ovidrel/Ovitrel). Any lesser dosage often will reduce the efficiency of meiosis and increase the risk of the eggs being aneuploid. I personally do not use the agonist (Lupron) “trigger”, unless it is combined with (low dosage) hCG. The supposed reason for using the agonist, (Lupron) “trigger” is that by inducing meiosis through compelling a surge in the release of LH by the pituitary gland, the risk it reduces the risk of OHSS. This may be true, but it comes at the expense of egg quality because the extent of the induced LH surge varies and if too little LH is released, meiosis can be compromised, thereby increasing the likelihood of aneuploid and immature (MI) eggs. And there are other better approaches to preventing OHSS (e.g. “prolonged coasting”), in my opinion.
Use of the Birth Control Pill (BCP) to launch IVF-COS.
In natural (unstimulated) as well as in cycles stimulated with fertility drugs, the ability of follicles to properly respond to FSH stimulation is dependent on their having developed FSH-responsive receptors. Pre-antral follicles (PAF) do not have such primed FSH receptors and thus cannot respond properly to FSH stimulation with gonadotropins. The acquisition of FSH receptor responsivity requires that the pre-antral follicles be exposed to FSH, for a number of days (5-7) during which time they attain “FSH-responsivity” and are now known as antral follicles (AF). These AF’s are now able to respond properly to stimulation with administered FSH-gonadotropins. In regular menstrual cycles, the rising FSH output from the pituitary gland insures that PAFs convert tor AF’s. The BCP (as well as prolonged administration of estrogen/progesterone) suppresses FSH. This suppression needs to be countered by artificially causing blood FSH levels to rise in order to cause PAF to AF conversion prior to COS commencing, otherwise pre-antral-to –antral follicle conversion will not take place in an orderly fashion, the duration of ovarian stimulation will be prolonged and both follicle and egg development may be compromised. GnRH agonists cause an immediate surge in release of FSH by the pituitary gland thus causing conversion from PAF to SAF. This is why women who take a BCP to launch a cycle of COS need to have an overlap of the BCP with an agonist. By overlapping the BCP with an agonist for a few days prior to menstruation the early recruited follicles are able to complete their developmental drive to the AF stage and as such, be ready to respond appropriately to optimal ovarian stimulation. Using this approach, the timing of the initiation of the IVF treatment cycle can readily and safely be regulated and controlled by varying the length of time that the woman is on the BCP.
Since optimizing follicular response to COS requires that prior to stimulation with gonadotropins, FSH-induced conversion from PAF to AF’s first be completed and the BCP suppresses FSH, it follows when it comes to women launching COS coming off a BCP something needs to be done to cause a rise in FSH for 5-7 days prior to menstruation heralding the cycle of CO S. This is where overlapping the BCP with a GnRHa comes in. The agonist causes FSH to be released by the pituitary gland and if overlapped with the BCP for several days and this will (within 2-5 days) facilitate PAF to AF conversion…. in time to start COS with the onset of menstruation. Initiating ovarian stimulation in women taking a BCP, without doing this is suboptimal.
I strongly recommend that you visit www.SherIVF.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
•The Fundamental Requirements For Achieving Optimal IVF Success
•Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
•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)
•Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
•Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
•Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
•Egg Maturation in IVF: How Egg “Immaturity”, “Post-maturity” and “Dysmaturity” Influence IVF Outcome:
•Commonly Asked Question in IVF: “Why Did so Few of my Eggs Fertilize and, so Many Fail to Reach Blastocyst?”
•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?
•Staggered IVF
•Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of 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.
•IVF: Selecting the Best Quality Embryos to Transfer
•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
•IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.
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ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.
Patients are encouraged to share the information I provide, with their treating Physicians and/or to avail themselves of my personal hands-on services, provided through batched IVF cycles that I conduct every 3 months at Los Angeles IVF (LAIVF) Clinic, Century City, Los Angeles, CA.
If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).
PLEASE SPREAD THE WORD ABOUT SFS!
Geoff Sher
Hi Dr.
I’m 31 yrs old I have a 6 yr old daughter concieved naturally, I have PCOS. We are now trying for baby number two its been a year, we tried ovulation induction with letrozole but have not been able to concieve. A laproscopy was performed and all was fine, the FS informed us that my anatomy is fine and the tubes are patent but due to my previous c-section she believes they have become attached to the anterior wall of the abdomen and may contribute to the reason why we are not able to concieve. We have now exhausted our letrozole and have been told to consider IVF. I also have psoriatic arthritis which is in remission I am not on any medication for it. I developed PSA after the daughters birth however I had psoriasis from teenave years.
My concern is will my psoriatic arthritis have any affect on IVF, I do have an ESR of 45 and CRP of 17 however I don’t have any pain.
Just wanting to go and have IVF done with the ease of my mind that psoriasis will not flare or interfere with it. Thank you so much
PSA might be an autoimmune condition and if so could be associated with an immunologic implantation dysfunction. WE should talk.
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) Why did my IVF Fail
•Recurrent Pregnancy Loss (RPL): Why do I keep losing my PregnanciesGenetically Testing Embryos for IVF
•Staggered IVF
•Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
•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.
•IVF: Selecting the Best Quality Embryos to Transfer
•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?
•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!
•Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
•Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
•A personalized, stepwise approach to IVF
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ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
I launched Sher-Fertility Solutions (SFS) in April 2019. Through SFS, I now provide guidance, through online Skype/FaceTime consultations to people with often complex Reproductive Issues, from > 40 countries. All consultations are followed by a detailed written report presenting my recommendations for treatment. Patients are encouraged to share this with their personal treating doctor(s) and/or to avail themselves of my hands-on IVF services, provided in batched cycles, conducted every 3 months at LAIVF in Century City, Los Angeles, CA.
If you wish to schedule a 1 hour , online consultation with me, please contact my assistant (Patti Converse) at 1-800-780-7437 or 702-533-2691. Alternatively , email Patti at concierge@SherIVF.com or enroll online at my website, http://www.SherIVF.com..
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Geoff Sher
What are your thoughts on Duo Stim for DOR patients?
I am aware of this approach but I do not believe it will help. It is still experimental!
Geoff Sher
Hi Dr Sher,
I have just had a failed FET. I have twins from my fresh cycle and the blastocyst we transferred a few weeks ago was from the same batch of embryos ( from when I was 34 years old) and was a grade 5CA and hatching. I understand that there are many reasons for a failed cycle, however I believe that a very traumatic transfer was a massive factor in why this cycle failed.
During my embryo transfer, the embryo was retained in the catheter on the first attempt. On the second attempt, I was told that the embryo had been successfully transferred. I chatted to the embryologist and consultant for a few minutes then left the room to get dressed. A few minutes later, I was informed by a nurse that my embryo had actually been found clinging on to the side of the catheter, obscured by some mucus. I was incredibly shocked. The consultant said that the embryo would need to be re-incubated for 30 minutes to protect it. I didn’t understand why this was necessary but a final transfer was performed an hour later after the embryo was re-cultured and incubated. The third transfer was apparently successful.
My question is whether this incident could have traumatised the embryo and caused damage? Also, the embryo transfer was performed by one embryologist loading the catheter and checking. Is it normal code of practice to have two embryologists double witness this crucial step of the procedure? And finally, no ultrasound guided transfer was offered and I feel that this may also impact the outcome.
I would love to know your thoughts about whether you believe the above factors may have impacted the viability of my embryo. I have one embryo left and I want to ensure this is prevented again. I have been advised that no harm could have come to my embryo as a result of this difficult transfer, but I am not so sure.
Many Thanks,
Karen
The embryo retention issue is sometimes unavoidable. However, 3 transfers is a bit much and could have an effect on the embryos. Most important from my perspective is failure to do the transfer with US guidance. The 30mn re-incubation is not unusual.
Geoff Sher
PH: 702-533-2691