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.
Hi Jessica,
I really do not know how far out I am booked. Call Julie at 800-780-7437 and ask her directly. Also, the consultation can be effected just as well, via Skype.
Geoff Sher
Also an extremely thing that I forgot to mention is: I have hyperhidrosis- which is an unclassified excessive sweating problem. I currently take glycopyrolate 2x a day/2mg dose. Will this drug cause interactions with any IUI medications? I already know stimulating myself with hormones will cause side effects of hot flashes that will only exacerbate my condition. Should I even try the IUI approach. I did inform my current doctor of this, but he has no insight as to how this would for me….
Hi Aziza,
I have no knowledge of possible effects of this drug. I would need to (and would) research this since it would be the first time in a career of 35y that I will have been confronted by this issue.
Geoff Sher
Hi Dr. Sher,
I am 35. In January I had 25 fibroids along with an ovarian cyst removed. As of June 2017, my HSG revealed a healthy uterine cavity with 4 more budding fibroids, a blocked tube, but a healthy ovary and an open tube on one side. The fertility clinic suggested that I start IUI rounds. I have never even tried to become pregnant naturally before, so I dont know of my chances in that aspect. Should I start with IUI or should I try the insemination at home?
Any guidance you can provide will be helpful.
Thanks,
Aziza Solomon
Before even contemplating treatment of any type, a thorough evaluation of your uterus and pelvic anatomy is essential. This will likely at the very least require a laparoscopy and hysteroscopy. Then we should talk.
Fibroids or leiomyomas are non-malignant muscle tumors that grow in the uterine wall. They can be found in about one out of every five (1:5) women >30Y of age. Fibroids are far more prevalent in African Americans and women and less frequent in other ethnic groups (i.e. Caucasians and Asians).
Fibroids, enlarge and/or distort uterine configuration. They can produce symptoms such as heavy, painful and prolonged menstrual periods. Other symptoms include pain with intercourse, backache, severe abdominal pain when large fibroids run out of blood supply or when superficial fibroids on a stem (pedunculated) undergo twisting (torsion). Sometimes fibroids will protrude into the uterine cavity, cause severe cramping and bleeding and so irritate the uterine lining as to compromise embryo attachment (anatomical implantation dysfunction). Women with fibroids are also at greater risk of miscarriage, premature delivery, malposition of the baby (mandating cesarean delivery) and an increased risk of bleeding after birth (post-partum hemorrhage)
Diagnosis can be made by one or more of the following symptoms/presentations: Symptomatology, pelvic examination pelvic ultrasound, hysterosalpingogram (HSG), sonohysterogram (HSN), CT-scan or MRI..
Fibroids are classified as:
•Submucosal: Here the fibroid grows just under the lining of the uterine cavity (mucosa) or protrudes into the uterine cavity. They might mold into the underlying uterine muscle (sessile) or be on a stalk (pedunculated). Submucosal fibroids can change the shape of the uterine cavity, irritate the lining and prevent implantation, cause miscarriage. These lesions must be removed in their entirety prior to undertaking embryo transfer, usually hysteroscopically. (see below)
•Subserosal: – Here the tumors grow under the outer layer (serosa) of the uterus. These fibroids will not compromise implantation, but if they are large, causing severe pain, and especially if they are multiple, pedunculated and thus at risk of undergoing torsion (twisting) the3y should be removed, usually laparoscopically. (See below).
•Intramural: – when the fibroids develop within the muscular wall of the uterus. This is the commonest presentation. Unless they are large and multiple and do not encroach on the uterine cavity, they can be left alone Surgical removal is usually by laparoscopy or laparotomy/abdominal open incision (See below)
The uterus is composed of a thick layer of smooth muscle (myometrium) surrounding the endometrial lining into which the embryo implants and which serves to protect and nourish a growing pregnancy. These tumors are rarely malignant (see below). Fibroid tumors, even large ones, can occur without producing any symptoms at all.
For the most part, only those fibroids that impinge upon the uterine (endometrial) cavity (submucosal) affect fertility. Exceptions include large fibroids in the muscle wall of the uterus (intramural) that can block the openings of the fallopian tubes as they enter the uterus, and where multiple fibroids cause abnormal uterine contraction patterns.
In some cases multiple uterine fibroids may so deprive the uterine lining (endometrium) of blood flow, that the delivery of estrogen to the endometrium is curtailed to the point that the lining cannot thicken sufficient to support a pregnancy. This can result in early 1st trimester (prior to the 13th week of pregnancy) miscarriages. Large or multiple fibroids, by curtailing the ability of the uterus to stretch in order to accommodate the spatial needs of a rapidly growing pregnancy, may precipitate 2nd trimester (beyond the 13th week) miscarriages and/or trigger the onset of premature labor.
Sizable fibroid tumors are usually easily identified by simple vaginal examination. However, even the smallest fibroid can be identified by transvaginal ultrasound. Sometimes it is difficult to tell if the fibroid is impinging on the uterine cavity. In such cases, a hysteroscopy (where a telescope like instrument, inserted via the vagina into the uterine cavity) or a sonohysterogram where injected fluid, distends the uterine cavity allowing for examination of its inner configuration can help distinguish between intramural and submucosal fibroids. CT scan and MRI can also be used to distinguish between fibroid tumors and another condition that also involves affects the uterine muscular wall, known as adenomyosis. This condition is characterized by endometrial tissue growing deeply into the uterine wall.. Given the often-diffuse nature of adenomyosis, it can be very difficult to remove surgically. This contrasts with fibroid tumors, which are well defined and are usually easily removed.
Surgical Treatment: The mainstay for the treatment of fibroid tumors is surgical removal (myomectomy). Small, asymptomatic fibroids that do not impinge upon the endometrial cavity will usually not require treatment other than observation and vigilance. Large fibroids and submucosal fibroids should be removed prior to starting fertility treatments such as In Vitro Fertilization (IVF) in order to decrease the chance of implantation failure, miscarriage, pregnancy complications and premature labor. Intramural and subserosal fibroids are readily removable by laparoscopic resection or via an abdominal incision. The former allows for a more rapid convalescence and is ideal for the removal of small and accessible superficial fibroid tumors, while the latter approach is preferred for treating larger and less accessible fibroids.
Myomectomy can affect fertility in several ways. If the endometrial cavity is entered during the surgery, there is a possibility of post adhesions forming within the uterine cavity. This should always be checked by the performance of a hysteroscopy or through a sonohysterogram, prior to beginning fertility treatment. Because myomectomy can be bloody, there is a high likelihood of post-operative abdominal adhesion formation, which could bind down or encase the ovaries, preventing the release of the eggs, or block the ends of the fallopian tubes. For this reason, it is important that myomectomies be formed only by accomplished surgeons, who are familiar with techniques to limit blood loss and prevent adhesion formation.
Regardless of whether the laparoscopic or abdominal approach is employed, adequate closure of the uterine wall is essential in order to reduce the subsequent risk of uterine rupture during pregnancy or labor. This is one of the main arguments used against the use of laparoscopic removal of large, multiple or remotely situated fibroids. While laparoscopic myomectomy requires but a few days (at most) for post-operative convalescence, abdominal myomectomy usually requires 6-8 weeks of recovery time. When myomectomy necessitates or results in the uterine cavity being entered (purposefully or inadvertently), it should always be followed up with a “2nd look” hysteroscopy to rule out scar tissue formation, which occurs frequently in the presence of submucosal fibroids.
Uterine polyps (and in some cases, also submucosal fibroids), can usually be removed hysteroscopically (through the vagina). This eliminates the need for abdominal surgery and greatly reduces the recovery time. Hysteroscopic surgery is only useful if the majority of the fibroid protrudes into the endometrial cavity, ensuring that the tumor defect will not be too large. This surgery is often done under laparoscopic guidance, to reduce the risk of uterine perforation. After hysteroscopic surgery it is often advisable to prescribe cyclical hormonal therapy for a few months to encourage regeneration of the endometrial lining over the area of tumor defect and healing of the uterine muscle. A 2nd look hysteroscopy should be performed a few months later in all cases, to rule out scar tissue formation even if it means delaying or deferring the initiation of definitive fertility treatment.
Medical Treatment: The growth of fibroid tumors is estrogen-dependent. Thus when a woman enters menopause and stops making female hormones, fibroids tend to shrink in size on their own. Conditions that mimic menopause can also reduce the size of fibroid tumors. The most common of theses treatment is with a medication such as leuprolide acetate (Lupron), which shuts off the communication of the brain with the ovaries, preventing hormone production. However, this type of medication can only be taken for a limited period (usually 6 months) and once the medication is stopped the fibroids will usually regain their original size within a few months. The medication is therefore only a “temporary fix,” used mostly to decrease the size of large fibroids in order to make their ultimate surgical removal easier, or to help a woman bridge the gap until spontaneous menopause sets in. For the majority of women there is no major benefit from Lupron therapy prior to surgery.
Embolization of Fibroid Tumors: Myomectomy always carries the small (although infrequent) risk that severe, uncontrollable intra-operative bleeding could require the performance of a hysterectomy (complete removal of the uterus) as a life saving measure. Moreover, some women are poor candidates for surgery. This is where a new procedure known as embolization comes in. Embolization is a procedure in which small particles are injected into the arteries of the uterus under radiological guidance to shut off the blood supply to the fibroids, in the hope that they will “shrink” and perhaps, even disappear.
Embolization is relatively new to the field of gynecology and little is known about its potential effects on future fertility. We are concerned that in the process of shutting off the blood supply to the uterus, it will permanently so reduce endometrial blood flow, as to compromise embryo implantation. For this reason, I do not currently recommend this therapy for women who still wish to conceive and carry a baby in their uterus. At present, it seems best suited for symptomatic women who are finished with their childbearing or who are planning to use a gestational surrogate.
Malignant Change in Fibroid Tumors: Fibroids rarely undergo malignant change. The reported incidence is less than 1 in 2000 cases. Fibroids usually grow very slowly (over a number of years). However, when growth occurs rapidly over a month or two, especially in older women who have large fibroids, it should raise the suspicion of this very rare but extremely serious complication.
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.
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•IVF Failure and Implantation Dysfunction:
•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!
•Endometrial Thickness, Uterine Pathology and Immunologic Factors
•Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
•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
•The Basic Infertility Work-Up
•Uterine Fibroids and Fertility
•Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s & Con’s!
•IUI-Reflecting upon its Use and Misuse: Time for a Serious “Reality Check”.
•Micro-IVF: Often Preferable to Ovarian Stimulation with or Without IUI
•Induction of Ovulation With Clomiphene Citrate: Mode of Action, Indications, Benefits, Limitations and Contraindications for its ue
•Clomiphene Induction of Ovulation: Its Use and Misuse!
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
I am 35 and my husband will be 36 this year. We have sperm motility issues. We have had one IVF (ICSI) cycle where one early morula (fragmented), and two early blastocysts (highly fragmented – graded poor) were transferred and the cycle failed. We moved on to do a second cycle for which we transferred one early morula (>40% fragmented, graded poor) and the cycle failed again. However from this second cycle, we have two frozen hatching blastocysts (graded excellent quality) that we plan to transfer later this month. I just had a hysteroscopy done last week and the doctor said that the uterus looks great. Could the reason for the early failures be only embryo quality? How do you see our chances for this FET cycle? We plan to transfer just one frozen blast.
It likely is an embryo quality issue, which although it can be due to sperm quality, is more likely a stimulation issue.
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.
•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.
•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
•Why did my IVF Fail
•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 Failure and Implantation Dysfunction:
•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!
•Endometrial Thickness, Uterine Pathology and Immunologic Factors
•Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
•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
•How Many Embryos should be transferred: A Critical Decision in IVF.
• Male Infertility
•Hormonal Treatment of Male Infertility
•Antisperm Antibodies, Infertility and the Role of IVF with Intracytoplasmic Sperm Injection (ICSI)
•Testicular Sperm Extraction (TESE) and Testicular Sperm Aspiration (TESA): Surgical Approaches for Accessing Sperm from men who have no sperm in their ejaculates (Azoospermia)
•Varicocele and Male Infertility: When and how should it be treated?
•The Sperm Chromatin Structure Assay (SCSA): A Measure of the Potential of Sperm to Help Propagate a Viable Pregnancy
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.
hello dr. Sher i also forgot to mention what’s the success rate with someone with pocos and hypothyroidisum I just turned 34 and I feel like I need to get it done now or at least try to do what I can to get Ivf done never done it before but I hope it will work thank u for taking the time to read and respond to message very much appreatiate
Thanks for communicating.
Herewith a few articles relating to 1) an under-active thyroid and its link to infertility and of]ten also repeated failed IVF and 2) to PCOS.
1)Between 2% and 5% of women of the childbearing age have reduced thyroid hormone activity (hypothyroidism). Women with hypothyroidism often manifest with reproductive failure i.e. infertility, unexplained (often repeated) IVF failure, or recurrent pregnancy loss (RPL). The condition is 5-10 times more common in women than in men. In most cases hypothyroidism is caused by damage to the thyroid gland resulting from of thyroid autoimmunity (Hashimoto’s disease) caused by damage done to the thyroid gland by antithyroglobulin and antimicrosomal auto-antibodies.
The increased prevalence of hypothyroidism and thyroid autoimmunity (TAI) in women is likely the result of a combination of genetic factors, estrogen-related effects and chromosome X abnormalities. This having been said, there is significantly increased incidence of thyroid antibodies in non-pregnant women with a history of infertility and recurrent pregnancy loss and thyroid antibodies can be present asymptomatically in women without them manifesting with overt clinical or endocrinologic evidence of thyroid disease. In addition, these antibodies may persist in women who have suffered from hyper- or hypothyroidism even after normalization of their thyroid function by appropriate pharmacological treatment. The manifestations of reproductive dysfunction thus seem to be linked more to the presence of thyroid autoimmunity (TAI) than to clinical existence of hypothyroidism and treatment of the latter does not routinely result in a subsequent improvement in reproductive performance.
It follows, that if antithyroid autoantibodies are associated with reproductive dysfunction they may serve as useful markers for predicting poor outcome in patients undergoing assisted reproductive technologies.
Some years back, I reported on the fact that 47% of women who harbor thyroid autoantibodies, regardless of the absence or presence of clinical hypothyroidism, have activated uterine natural killer cells (NKa) cells and cytotoxic lymphocytes (CTL) and that such women often present with reproductive dysfunction. We demonstrated that appropriate immunotherapy with IVIG or intralipid (IL) and steroids, subsequently often results in a significant improvement in reproductive performance in such cases.
The fact that almost 50% of women who harbor antithyroid antibodies do not have activated CTL/NK cells suggests that it is NOT the antithyroid antibodies themselves that cause reproductive dysfunction. The activation of CTL and NK cells that occurs in half of the cases with TAI is probably an epiphenomenon with the associated reproductive dysfunction being due to CTL/NK cell activation that damages the early “root system” (trophoblast) of the implanting embryo. We have shown that treatment of those women who have thyroid antibodies + NKa/CTL using IL/steroids, improves subsequent reproductive performance while women with thyroid antibodies who do not harbor NKa/CTL do not require or benefit from such treatment.
2)Polycystic ovary syndrome (PCOS) is a common hormonal system disorder among women affecting between 5% and 10% of women of reproductive age worldwide. Women with PCOS may have enlarged ovaries that contain small collections of fluid — called follicles — located in each ovary as seen during an ultrasound. The condition is characterized by abnormal ovarian function (irregular or absent periods, abnormal or absent ovulation and infertility), androgenicity (increased body hair or hirsutism, acne) and increased body weight –body mass index or BMI. The ovaries of women with PCOS characteristically contain multiple micro-cysts often arranged like a “string of pearls” immediately below the ovarian surface (capsule).interspersed by an overgrowth of ovarian connective tissue (stroma).
PCOS is one of the most common causes of menstrual irregularities, infertility, and hirsutism, Despite an enormous effort to define its cause, the etiology of PCOS remains unclear, and there is no definite cure at this time. PCOS is clearly a heterogeneous disorder which often has a familial (genetic) basis. Infertility associated with PCOS has been attributed to numerous factors, including dysfunctional gonadotropin pituitary secretion, peripheral insulin resistance, elevated adrenal and/or ovarian androgen (male hormone) levels, and dysfunction of several growth factors. Women with this condition are often obese and insulin resistant. The compensatory hyperinsulinemia further stimulates ovarian androgen production which may be detrimental to egg maturation and there is a clear link between the degree of insulin resistance and anovulation. PCOS is also a significant long-term health risk for women, thus necessitating vigilance through regular annual examinations (non-insulin dependent diabetes mellitus, hypertension, hypercholesterolemia, cardiovascular disease and endometrial cancer). Whereas PCOS-related infertility is usually manageable through the use of fertility drugs, lifestyle changes (diet and exercise) remain a mainstay of long-term therapy. More recently, ovulation rates, circulating androgens, pregnancy rates and perhaps even first-trimester miscarriage rates have been shown to improve when insulin sensitizers like metformin are used to correct the underlying insulin resistance.
Most patients with PCOS are young and have excellent pregnancy rates with oral clomiphene. Those that require more aggressive treatments with injectable medications probably represent a subgroup of PCOS patients with severe ovarian dysfunction. These women often have explosive response to gonadotropins which can result in serious complications like Severe Ovarian Hyperstimulation Syndrome (OHSS…see below) and high order multiple births. In those women, the ability to perform “prolonged coasting” (see below) and selectively transfer fewer embryos during IVF offers a clear advantage over standard gonadotropin injections.
Egg quality in PCOS
The potential for a woman’s eggs to undergo orderly maturation, successful fertilization and subsequent progression to “good quality embryos” is in large part genetically determined. However, the expression of such potential is profoundly susceptible to numerous influences, especially intra-ovarian hormonal changes during the pre-ovulatory phase of the cycle. Proper follicular stimulation as well as precise timing of egg maturation with LH (Luteinizing Hormone) or hCG (human chorionic gonadotropin) is crucial to optimal egg maturation, fertilization and ultimately embryo quality. Both pituitary gonadotropins, LH and FSH (follicle stimulating hormone) play a pivotal but different role in follicular development. The action of FSH is mainly directed toward granulosa cell (cells lining the inside of the follicle) proliferation and estrogen production (E2). LH, on the other hand, acts primarily on the ovarian stroma (the connective tissue that surrounds the follicle) to produce androgens. While small amounts of ovarian androgens, such as testosterone, enhance egg and follicle development, over-exposure to them can have a deleterious effect. Furthermore, excessive ovarian androgens can also compromise estrogen-induced endometrial growth and development.
Suppressing pituitary secretion of LH with gonadotropin releasing hormone (GnRH) agonists such as Lupron®, is particularly useful in PCOS. In that condition, serum LH levels are elevated, leading to stromal overgrowth, follicular arrests (so-called cysts) and high levels of androgens synthesis. It is therefore not surprising that these follicles often yield poorly developed (“immature”) eggs” at the time of egg retrieval (ET) and that “poor egg/embryo quality”, inadequate endometrial development and high miscarriage rates are common features of this condition. However, contrary to popular belief, this is not due to an intrinsic deficit in “egg quality”. Stimulation protocols geared toward optimizing follicle and egg development and avoiding over exposure to androgens correct these problems ad result in pregnancy rates similar to those of non-PCOS women. Whereas the overuse of LH-containing preparations such as Menopur® and Luveris® further aggravates this effect. In conclusion, to maximize ultimate oocyte maturation, we strongly recommend against the exclusive use of such products in PCOS patients, preferring FSH-dominant products such as Folistim®, Gonal F® or Bravelle® over a period of at least 9 days following pituitary suppression with Lupron®.
PCOS women often have a family history of diabetes and demonstrable insulin resistance (evidenced by high blood insulin levels and an abnormal 2-hour glucose tolerance test).This underlying Diabetes mellitus tendency could play a role in the development of PCOS and contribute to the development of obesity, an abnormal blood lipid profile, and a predisposition to coronary vascular disease. Women with PCOS are slightly more at risk of developing uterine, ovarian and possibly also breast cancer in later life and accordingly should be evaluated for these conditions on a more frequent basis than would ordinarily be recommended to non-PCOS women.
Most women with PCOS either do not ovulate at all or they ovulate irregularly. As a consequence thereof they in addition usually experience delayed, absent or irregular menstruation. In addition, an inordinate percentage of the eggs produced by PCOS women following ovulation induction, tend to be chromosomally abnormal (aneuploid). Rather than being due to an intrinsic egg defect being inherent in PCOS women, the poor egg quality more than likely the result of over-exposure to male hormones (predominantly, testosterone) produced by the ovarian stroma. These two factors (ovulation dysfunction and poor egg quality) are the main reasons for the poor reproductive performance (infertility and an increased miscarriage rate) in PCOS women.
PCOS patients are at an inordinate risk of severely over-responding fertility drugs, both oral varieties (e.g. Clomiphene, Serophene & Femara) and especially the injectables (e.g. Follistim, Puregon, Gonal F, Menopur and Bravelle) by forming large numbers ovarian follicles. This can lead to life endangering complications associated with sever ovarian hyperstimulation (OHSS). In addition PCOS women receiving fertility drugs often experience multiple ovulations putting them at severe risk (40%+) of high order multiple pregnancy (i.e. triplets or greater) with often devastating consequences.
VARIETIES OF POLYCYSTIC OVARIAN SYNDROME:
1) Hypothalamic-pituitary-PCOS: This is the commonest form of PCOS and is often genetically transmitted and is characteristically associated with a blood concentration of Luteinizing Hormone (LH) that is uncharacteristically much higher than the Follicle Stimulating Hormone (FSH) level (FSH is normally higher than the LH concentration) as well as high-normal or blood androgen ( male) hormone concentrations (e.g. androstenedione, testosterone and dehydroepiandrosterone -DHEA).Hypothalamic-pituitary-ovarian PCOS is also often associated with insulin resistance and in about 40%-50% of the cases.
2) Adrenal PCOS: Here the excess of male hormones are derived from overactive adrenal glands rather than from the ovaries. Blood levels of testosterone and/or androstenedione raised but here, but here, the blood level of dehydroepiandrosterone (DHEAS) is also raised, clinching the diagnosis.
3) Severe pelvic adhesive disease secondary to severe endometriosis, chronic pelvic inflammatory disease and/or extensive pelvic surgery: Women who have this type of PCOS tend to less likely to hyperstimulate in response to ovulation induction . Their. DHEAS is also is not raised.
TREATMENT OF INFERTILITY DUE TO ASSOCIATED OVULATION DYSFUNCTION:
Hypothalamic-pituitary-/ovarian PCOS: Ovulation induction with fertility drugs such as clomiphene citrate, Letrozole (Femara) or gonadotropins, with or without intrauterine insemination (IUI) is often highly successful in establishing pregnancies in PCOS women. However, IVF is fast becoming a treatment of choice (see below).
In about 40% of cases, 3-6 months of oral Metformin (Glucophage) treatment results in a significant reduction of insulin resistance, lowering of blood androgen levels, an improvement in ovulatory function, and/or some amelioration of androgenous symptoms and signs.
Surgical treatment by “ovarian drilling” of the many small ovarian cysts lying immediately below the envelopment (capsule) of the ovaries, is often used, but is less successful than alternative non-surgical treatment and is only temporarily effective. The older form of surgical treatment, using ovarian wedge resection is rarely used any longer as it can produce severe pelvic adhesion formation.
Adrenal PCOS is treated with steroids such as prednisone or dexamethasone which over a period of several weeks will suppress adrenal androgen production, allowing regular ovulation to take place spontaneously. This is often combined with clomiphene, Letrozole and/or gonadotropin therapy to initiate ovulation.
PCOS attributable to Pelvic Adhesive Disease is one variety which often is associated with compromised ovarian reserve, a raised FSH blood level and ovarian resistance to fertility drugs. In many such cases, high dosage of gonadotropins (FSH-dominant) with “estrogen priming” will often elicit an ovarian response necessary for successful ovulation induction and/or IVF. Neither steroids nor Metformin are helpful in the vast majority of such cases.
PCOS women undergoing ovulation induction usually release multiple eggs following the hCG trigger and are thus at inordinate risk of twin or higher order multiple pregnancies. They are also at risk of developing OHSS. Many now believe that IVF should be regarded as a primary and preferential treatment for PCOS. The reason is that it is only through this approach that the number of embryos reaching the uterus can be controlled and in this manner the risk of high-order multiples can be minimized and it is only in the course of IVF treatment that a novel treatment method known as “prolonged coasting” ( see below) which prevents OHSS, can be implemented
SEVERE OVARIAN HYPERSTIMULATION SYNDROME (OHSS):
As indicated above, there is an inordinate propensity for women with PCOS to hyper-respond to gonadotropin fertility drugs and in the process produce large numbers of ovarian follicles. If left unchecked this can lead to OHSS, a potentially life endangering condition. The onset of OHSS is signaled by the development of a large number of ovarian follicles (usually more than 25 in number). This is accompanied by rapidly rising plasma estradiol (E2) levels, often exceeding 3000pg/ml within 7 or 9 days of stimulation, often rapidly peaking above 6,000 pg/ml prior to hCG administration. When this happens, the risk of OHSS developing is above 80%.
Symptoms and signs of OHSS include: abdominal distention due to fluid collection (ascites), fluid in the chest cavity (hydrothorax), rapid weight gain (of a pound or more per day) due to tissue fluid retention, abdominal pain, lower back ache, nausea, diarrhea, vomiting, visual disturbances such as blurred vision and spots in front of the eyes (scotomata), a rapidly declining urine output, cardiovascular collapse and failure of blood to clot which sometimes results in severe bruising (echymosis) and frank bleeding. These symptoms and signs may appear before pregnancy can be diagnosed. If pregnancy occurs, the condition is likely to worsen progressively over a period of 3-5 weeks whereupon it rapidly resolves spontaneously over a few days. If no pregnancy occurs, the symptoms and signs all disappear spontaneously within 10-12 days of the hCG injection.
When increasing fluid collection in the abdominal cavity (ascites) starts to compromise breathing raising the head of the bed rose slightly by placing a 4-6 inch block at the base of each head post and using a few additional pillows, will sometimes help ameliorate the problem. In cases where this does not help or symptoms become severe, all or most of the fluid can readily and safely be drained through t transvaginal sterile needle aspiration (vaginal paracentesis-performed once or sometimes twice a week) can be performed once or twice weekly . The problem will usually self corrects within 10-12 days of the hCG shot if pregnancy does not occur or, by the 8th week of pregnancy.
Urine output should be monitored daily to see if it drops below about 500ml a day (about two cups and a half). A chest X-ray, to evaluate for fluid collection in the chest and around the heart should be done weekly along with blood tests for hematocrit, BUN, electrolytes, creatinine, platelet count and fibrin split products (FSP). If indicated on the basis of a deteriorating clinical situation, hospitalization might be needed for close observation and if necessary, to provide intensive care.
In all case of OHSS, the ovaries will invariably be considerably enlarged. This is irrelevant to the final outcome, unless ovarian torsion (twisting of the ovary on its axis), an extremely rare complication occurs. The latter would usually require surgical emergency surgical intervention.
It is important to know that symptoms and signs of OHSS are severely aggravated by rising hCG levels. Thus such patients should not receive additional hCG injections.
Does PCOS cause poor egg/embryo quality? It is an undeniable fact that women with PCOS undergoing IVF are commonly found to have poorly developed (“dysmorphic”) eggs, with reduced fertilization potential and yielding “poor quality embryos”. However, in the author’s opinion (which admittedly runs contrary to popular opinion), this is unlikely to be due to an intrinsic deficit in egg quality. Rather, it more likely relates to intra-ovarian hormonal changes brought about by hyperstimulation and which compromise egg development. This effect, in the author’s opinion, can often be significantly reduced through implementation of an individualized or customized ovarian stimulation protocols that minimize exposure of the developing follicles and eggs to excessive LH-induced ovarian androgens. This can be best achieved by limiting the use of LH-containing gonadotropins such as Menopur through selective institution of “prolonged coasting” (see below).
In the past, the onset of OHSS, heralded by the presence of large numbers of developing ovarian follicles and rapidly rising plasma estradiol levels often led the treating physician to prematurely administer hCG in an attempt to abruptly arrest the process and prevent escalation of risk to the patient. However the premature administration of hCG, while abruptly arresting further proliferation of estrogen producing granulosa cells in the follicles, unfortunately also prematurely arrests egg development. Since the ability of an egg to achieve optimal maturation upon hCG triggering is largely predicated upon it having achieved prior optimal development, the untimely administration of hCG which triggers meiosis, probably increases the risk of numerical chromosomal abnormalities (aneuploidy) of the egg. This in turn would lead to reduced fertilization potential, poor egg/embryo quality and low embryo implantation potential.
In women with PCOS the connective tissue that surrounding the follicles (ovarian stroma) is often characteristically overgrown (stromal hyperplasia). It is the stroma that produces androgens (mainly testosterone) in response to LH. It is this, coupled with the fact that PCOS women also often have elevated blood LH concentrations (see above) results in the excessive production of androgen hormones, which is so characteristic in PCOS. While excessive exposure of developing eggs to ovarian androgens compromises follicle and egg growth it also impairs endometrial response to estrogen, which could explain the common finding of poor endometrial thickening in many PCOS women undergoing IVF.
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The obvious remedy for these adverse effects on egg and endometrial development is to employ stimulation protocols that limit ovarian over-exposure to LH and allowing the time necessary for the follicles/eggs to develop optimally, prior to administering hCG through the judicious implementation of “Prolonged coasting” (PC).
“PROLONGED COASTING”:
In the early 90’s we were the first to report on “prolonged coasting” (PC), a novel approach that protects egg quality while preventing the development of OHSS. PC has since, gained widespread acceptance as a method of choice for preventing OHSS and has established itself as the “standard of care”. It involves withholding gonadotropin therapy while continuing the administration of the GnRHa and waiting until the plasma estradiol concentration drops below 2,500 pg/ml. Thereupon hCG is administered. In such cases, regardless of the number of developed follicles or the number of eggs retrieved, these women rarely, if ever develop OHSS. It has been reported that while PC virtually eliminates the risk of life-endangering complications associated with OHSS, there are reports in the literature that “the price to pay with PC” is often a poorer fertilization rate and reduced embryo implantation potential, compromising the pregnancy”. It is the author’s opinion an experience in the development of PC that egg/embryo quality deficit likely has little to do with the process of PC, itself and can be explained as follows: When PC is initiated too early, follicle growth and development may cease (as evidenced by the estradiol level plateauing or falling immediately, rather than showing an initial continued increase), and when PC is started too late, the follicles will often become cystic, measuring >21mm by the time the estradiol level falls below the safe threshold of 250000pg/ml, and so harbor dysmorphic eggs. Thus precise timing of the initiation of PC is critical. It should in pact be initiated preemptively in all cases when there are more than 25 follicles and the plasma estradiol reaches or exceeds 2,500pg/ml in association, provided that at least 50% of the follicles measuring 14-16mm in mean diameter. Not a day sooner or a day later. If PC is initiated with precise timing, it will usually be followed by a further progressive rise in the estradiol concentration. After a few days, the estradiol level will plateau and then it will start to fall (often rapidly). The temptation to trigger with hCG before the estradiol level falls below 3000picogtrams per milliliter must be resisted …even if the level falls below 1,000pg/ml by the time hCG is given.
Since when using agonist ( Cetrotide/Ganirelix/Orgalutron) pituitary suppression throughout the stimulation phase with gonadotropins, the plasma estradiol level often under expressed follicle growth, this method of pituitary blockade should not be used in cases ( such as with PCOS) where PC might be required.,
Prolonged coasting prevents canceled cycles and with it, canceled dreams.
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.
•Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•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
•IVF: How Many Attempts should be considered before Stopping?
•“Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
•IVF Failure and Implantation Dysfunction:
•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!
•Endometrial Thickness, Uterine Pathology and Immunologic Factors
•Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
•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
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