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.
Hello,
I just recently went through the whole process to freeze my eggs. I started off with birth control then I was put on cetrotide, gonal f, and micro ovidrel. All of my ultrasounds went well, I responded well to the medications and all my levels were great. I used the lupron trigger shot and was told the next day that my body responded like it should to the trigger shot and I was ready for egg retrieval the following day. I had many follicles that were at the right size. After I woke up from my egg retrieval I was told that zero eggs were retrieved. I was so confused and hurt at the same time. The doctor that had been overseeing me prior to the egg retrieval was not the one on call to do surgeries that day so another doctor did my egg retrieval. I wasn’t given a concrete answer of what went wrong and I demanded that my doctor call me. She called and said that the eggs are there but they haven’t “surfaced” I was told to trigger that night again but this time with HCG shot and not lupron. The following morning I was instructed to take a pregnancy test which needed to read positive. I did this and it was positive. I was told the hcg shot worked and I would have the egg retrieval process repeated the following day. When I went for my second egg retrieval my dr did an ultrasound because she wanted to make sure there were follicles present before they performed the surgery on me!!!!! I was so upset at that point because that’s when I discovered that the first doctor that performed my egg retrieval had drained all of my follicles. Why, why why???? If there were over 10, 15 or however many follicles why wouldn’t have he stopped after maybe the 3rd empty follicle of there was a chance to trigger and try again. My dr said there were some follicles and it was WORTH A TRY!! She retrieved 4 eggs and only 2 made it…….does anyone else see something wrong with this?
It sounds as if you have normal ovarian reserve. In my opinion, all this is likely to be linked to the protocol used for ovarian stimulation. However to advise authoritatively, I need more information. I think you would benefit from a Skype consultation with me (see below).
Here is the protocol I advise for women who have adequate ovarian reserve.
My advice is to use a long pituitary down regulation protocol starting on a BCP, and overlapping it with Lupron 10U daily for three (3) days and then stopping the BCP but continuing on Lupron 10u daily (in my opinion 20U daily is too much) and await a period (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst and simultaneously, the Lupron dosage is reduced to 5U daily to be continued until the hCG (10,000u) trigger. An FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is started with the period for 2 days and then the gonadotropin dosage is reduced and a small amount of menotropin (Menopur—no more than 75U daily) is added. This is continued until US and blood estradiol levels indicate that the hCG trigger be given, whereupon an ER is done 36h later. I personally would advise against using Lupron in a “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.
For women doing conventional IVF with a fresh embryo transfer, I usually add dexamethasone 0.75mg daily from the start of gonadotropin stimulation to the 8th week of pregnancy (and then is tailed of and stopped by the 10th week) and human growth hormone (HGH) daily from the 1st day of Lupron, up until the trigger with hCG. Women who test positive for Natural killer cell activation (Nka), receive an Intralipid (IL) infusion 10-14 days prior to the projected embryo transfer This is repeated with a +ve beta hCG pregnancy test result.
Those women, who for a variety of reasons do frozen embryo transfers (FET) and thus do not undergo embryo transfer in the same cycle as the egg retrieval, can omit taking the dexamethasone in the cycle of ER, deferring such to the subsequent FET cycle. They do however take HGH throughout the stimulation with gonadotropin and if they test positive for Nka, they will also receive dexamethasone during hormonal preparation for FET (continued until the 8th week of pregnancy when this is tailed off over 2 weeks and stopped by the 10th week.
I strongly recommend that you visit http://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
• 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.
• 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
• “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
Geoff Sher
___________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.
Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .
PLEASE HELP SPREAD THE WORD ABOUT SFS!
Geoff Sher
Dr. Sher,
We are reaching out to you because we are 12 years into our infertility struggle. We have had 5 unsuccessful rounds of IUI and 2 unsuccessful rounds of IVF. It took its toll on our marriage, so we took 8 1/2 years off thinking we would never again try to conceive. We went back to the same clink last month and we were told that they beleive we were unsuccessful because of a male factor called dna fragmentation. My husband had a varicocele removed 9 years ago and still have one that is hard to get to. His numbers improved, but motility was still an issue, so they said IVF would get rid of the male factor. It didn’t. I developed OHSS with the first round. The dr worried about this very early on, so he lessened my doses. He extracted 29 eggs. All made it and all fertilized. They basically stopped doing anything at day 3. The second round he decided to lessen my dose even more. He extracted 33 eggs. Froze them in case I developed OHSS again. All thawed and all fertilized. Again, they stopped doing anything after day 3. They now believe it was becuase of DNA fragmentation. I am now 38. They checked my follicle count on day 3 of my cycles, and they stopped counting at 41. I don’t know if that’s good or bad. I’m afraid of another failed cycle.
We would appreciate any advice you have. You gave a good friend of mine great advice that she followed and she now has a beautiful girl.
Thank you so much for your time.
Very respectfully Kari, I do not agree with the explanation you have been given. In my opinion, the poor embryo progression is likely to be linked to egg quality and in my opinion is less likely to be as function of sperm DNA fragmentation issues. When it comes to women who are high-responders such as you are, the protocol of stimulation used makes a major difference. Yours needs to be individualized.
The potential for a woman’s eggs to undergo orderly development and maturation, while in large part being genetically determined can be profoundly influenced by the woman’s age, her “ovarian reserve” and proximity to menopause. It is also influenced by the protocol used for controlled ovarian stimulation (COH) which by fashioning the intra-ovarian hormonal environment, profoundly impacts egg development and maturation.
After the menarche (age at which menstruation starts) a monthly process of repeatedly processing eggs continues until the menopause, by which time most eggs will have been used up, and ovulation and menstruation cease. When the number of eggs remaining in the ovaries falls below a certain threshold, ovarian function starts to wane over a 5 to10-years. This time period is referred to as the climacteric. With the onset of the climacteric, blood Follicle Stimulating Hormone (FSH) and later also Luteinizing Hormone (LH) levels begin to rise…. at first slowly and then more rapidly, ultimately culminating in the complete cessation of ovulation and menstruation (i.e. menopause).
One of the early indications that the woman has entered the climacteric and that ovarian reserve is diminishing DOR) , is the detection of a basal blood FSH level above 9.0 MIU/ml and/ or an AMH level og <2.0ng/ml.
Prior to the changes that immediately precede ovulation, virtually all human eggs have 23 pairs (i.e. 46) of chromosomes. Thirty six to forty hours prior to ovulation, a surge occurs in the release of LH by the pituitary gland. One of the main e purposes of this LH surge is to cause the chromosomes in the egg to divide n half (to 23 in number) in order that once fertilized by a mature sperm ends up having 23 chromosomes) the resulting embryo will be back to having 46 chromosomes. A “competent” mature egg is one that has precisely 23 chromosomes, not any more or any less. It is largely the egg, rather than the sperm that determines the chromosomal integrity of the embryo and only an embryo that has a normal component of 46 chromosomes (i.e. euploid) is “competent” to develop into a healthy baby. If for any reason the final number of chromosomes in the egg is less or more than 23 (aneuploid), it will be incapable of propagating a euploid, “competent” embryo. Thus egg/embryo aneuploidy (“incompetence”) is the leading cause of human reproductive dysfunction which can manifest as: arrested embryo development and/or failed implantation (which often presents as infertility), early miscarriage or chromosomal birth defects (e.g. Down’s syndrome). While most aneuploid (“incompetent”) embryos often fail to produce a pregnancy, some do. However, most such pregnancies miscarry early on. On relatively rare occasions, depending on the chromosome pair involved, aneuploid embryos can develop into chromosomally defective babies (e.g. Down’s syndrome).
Up until a woman reaches her mid- thirties, at best, 1:2 of her eggs will likely be chromosomally normal. As she ages beyond her mid-thirties there will be a a progressive decline in egg quality such that by age 40 years only about 15%-20% of eggs are euploid and, by the time the woman reaches her mid-forties, less than 10% of her eggs are likely to be chromosomally normal. While most aneuploid embryos do appear to be microscopically abnormal under the light microscope, this is not invariably so. In fact, many aneuploid embryos a have a perfectly normal appearance under the microscope. This is why it is not possible to reliably differentiate between competent and incompetent embryos on the basis of their microscopic appearance (morphologic grade) alone.
The process of natural selection usually precludes most aneuploid embryos from attaching to the uterine lining. Those that do attach usually do so for such only a brief period of time. In such cases the woman often will not even experience a postponement of menstruation. There will be a transient rise in blood hCG levels but in most cases the woman will be unaware of even having conceived (i.e. a “chemical pregnancy”). Alternatively, an aneuploid embryo might attach for a period of a few weeks before being expelled (i.e. a “miscarriage”). Sometimes (fortunately rarely) an aneuploid embryo will develop into a viable baby that is born with a chromosomal birth defect (e.g. Down’s syndrome).
The fact that the incidence of embryo aneuploidy invariably increases with advancing age serves to explain why reproductive failure (“infertility”, miscarriages and birth defects), also increases as women get older.
It is an over-simplification to represent that diminishing ovarian reserve as evidenced by raised FSH blood levels (and other tests) and reduced response to stimulation with fertility drugs is a direct cause of “poor egg/ embryo quality”. This common misconception stems from the fact that poor embryo quality (“incompetence”) often occurs in women who at the same time, because of the advent of the climacteric also have elevated basal blood FSH/LH levels and reduced AMH. But it is not the elevation in FSH or the low AMH that causes embryo “incompetence”. Rather it is the effect of advancing age (the “biological clock”) resulting a progressive increase in the incidence of egg aneuploidy, which is responsible for declining egg quality. Simply stated, as women get older “wear and tear” on their eggs increases the likelihood of egg and thus embryo aneuploidy. It just so happens that the two precipitating factors often go hand in hand.
The importance of the IVF stimulation protocol on egg/embryo quality cannot be overstated. This factor seems often to be overlooked or discounted by those 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 in patients at risk – particularly those with diminished ovarian reserve (“poor responders”) and those who are “high responders” (women with PCOS , those with dysfunctional or absent ovulation, and young women under 25 years of age).
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.
During the normal ovulation cycle, ovarian hormonal changes are regulated to avoid irregularities in production and interaction that could adversely influence follicle development and egg quality. As an example, small amounts of androgens (male hormones such as testosterone) that are produced by the ovarian stroma (the tissue surrounding ovarian follicles) during the pre-ovulatory phase of the cycle enhance late follicle development, estrogen production by the granulosa cells (cells that line the inner walls of follicles), and egg maturation.
However, over-production of testosterone can adversely influence the same processes. It follows that protocols for controlled ovarian stimulation (COS should be geared toward optimizing follicle growth and development (without placing the woman at risk from overstimulation), while at the same time avoiding excessive ovarian androgen production. Achievement of such objectives requires a very individualized approach to choosing the protocol for COS with fertility drugs as well as the precise timing of the “trigger shot” of hCG.
It is important to recognize that the pituitary gonadotropins, LH and FSH, while both playing a pivotal role in follicle development, have different primary sites of action in the ovary. The action of FSH is mainly directed towards the cells lining the inside of the follicle that are responsible for estrogen production. LH, on the other hand, acts primarily on the ovarian stroma to produce male hormones/ androgens (e.g. androstenedione and testosterone). A small amount of testosterone is necessary for optimal estrogen production. Over-production of such androgens can have a deleterious effect on granulosa cell activity, follicle growth/development, egg maturation, fertilization potential and subsequent embryo quality. Furthermore, excessive ovarian androgens can also compromise estrogen-induced endometrial growth and development.
In conditions such as polycystic ovarian syndrome (PCOS), which is characterized by increased blood LH levels, there is also increased ovarian androgen production. It is therefore not surprising that “poor egg/embryo quality” is often a feature of this condition. The use of LH-containing preparations such as Menopur further aggravates this effect. Thus we recommend using FSH-dominant products such as Follistim, Puregon, and Gonal-F in such cases. While it would seem prudent to limit LH exposure in all cases of COS, this appears to be more vital in older women, who tend to be more sensitive to LH
It is common practice to administer gonadotropin releasing hormone agonists (GnRHa) agonists such as Lupron, and, GnRH-antagonists such as Ganirelix and Orgalutron to prevent the release of LH during COS. GnRH agonists exert their LH-lowering effect over a number of days. They act by causing an initial outpouring followed by a depletion of pituitary gonadotropins. This results in the LH level falling to low concentrations, within 4-7 days, thereby establishing a relatively “LH-free environment”. GnRH Antagonists, on the other hand, act very rapidly (within a few hours) to block pituitary LH release, so as achieve the same effect.
Long Agonist (Lupron/Buserelin) Protocols: The most commonly prescribed protocol for Lupron/gonadotropin administration is the so-called “long protocol”. Here, Lupron is given, starting a week or so prior to menstruation. This results in an initial rise in FSH and LH level, which is rapidly followed by a precipitous fall to near zero. It is followed by uterine withdrawal bleeding (menstruation), whereupon gonadotropin treatment is initiated while daily Lupron injections continue, to ensure a “low LH” environment. A modification to the long protocol which I prefer using in cases of DOR, is the Agonist/Antagonist Conversion Protocol (A/ACP) where, upon the onset of a Lupron-induced bleed , this agonist is supplanted by an antagonist (Ganirelix/Cetrotide/Orgalutron) and this is continued until the hCG trigger. In many such cases I supplement with human growth hormone (HGH) to try and further enhance response and egg development.
Lupron Flare/Micro-Flare Protocol: Another approach to COS is by way of so-called “(micro) flare protocols”. This involves initiating gonadotropin therapy simultaneous with the administration of GnRH agonist (e.g. Lupron/Buserelin). The intent here 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” represents “a double edged sword” because 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 androgen production which could potentially compromise egg quality, especially in older women and women with PCOS, whose ovaries have increased sensitivity to LH. 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 in older women, and in women with diminished ovarian reserve. Accordingly, I do not prescribe them at all.
Estrogen Priming – My approach for “Poor Responders” Our patients who have demonstrated reduced ovarian response to COS as well as those who by way of significantly raised FSH blood levels are likely to be “poor responders”, are treated using a “modified” long protocol. The approach involves the initial administration of GnRH agonist for a number of days to cause pituitary down-regulation. Upon menstruation and confirmation by ultrasound and measurement of blood estradiol levels that adequate ovarian suppression has been achieved, the dosage of GnRH agonist is drastically lowered and the woman is given twice-weekly injections of estradiol for a period of 8. COS is thereupon initiated using a relatively high dosage of FSH-(Follistim, Bravelle, Puregon or Gonal F) which is continued along with daily administration of GnRH agonist until the “hCG trigger.” By this approach we have been able to significantly improve ovarian response to gonadotropins in many of hitherto “resistant patients”.
The “Trigger”: hCG (Profasi/Pregnyl/Novarel) versus Lupron: With ovulation induction using fertility drugs, the administration of 10,000U hCGu (the hCG “trigger”) mimics the LH surge, sending the eggs (which up to that point are immature (M1) and have 46 chromosomes) 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 it had prior to the “trigger”. Such a chromosomally normal, M2 egg, upon being fertilized by mature sperm (that following maturational division also has 23 chromosomes) will hopefully propagate embryos that have 46 chromosomes and will be “:competent” to propagate viable pregnancies. The key is to trigger with no less than 10,000U of hCGu (Profasi/Novarel/Pregnyl) and if hCGr (Ovidrel) is used, to make sure that 500mcg (rather than 250mcg) is administered. In my opinion, any lesser dosage will reduce the efficiency of meiosis, and increase the risk of the eggs being chromosomally abnormal. . I also do not use the agonist (Lupron) “trigger”. This approach which is often recommended for women at risk of overstimulation, is intended to reduce the risk of OHSS. The reason for using the Lupron trigger is that by inducing a surge in the release of LH by the pituitary gland it reduces the risk of OHSS. This is true, but this 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 percentage of chromosomally abnormal and of immature (M1) eggs. The use of “coasting” in such cases) can obviate this effect
.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.
___________________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.
Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .
PLEASE HELP SPREAD THE WORD ABOUT SFS!
Geoff Sher
Obviously, I need much more information to be able to authoritatively advise you with confidence. However, I think I can help, but to do so we need to talk.
Dear Dr. Sher,
I was wondering if there really is such a thing as a “late implanter”? I am a biologist and I can not explain such phenomenon. I am 7 days post 5 day transfer (3AA blastocyst) and the home pregnancy test still shows a negative (sensitivity 12 IU/ml). Can I assume this cycle did not work?
I think it is too early to reach that conclusion. I would wait a few days and do a quantitative hCG test.
Good luck!
Geoff Sher
Hello Dr. Sher,
I enjoy reading through previous questions and learning a lot about my own journey. I am trying to make a responsible decision about iui and I can’t find an information on the question I have.
My understanding is your estradiol is usually 200 units for each mature egg. I have an estradiol level of 780 but I have 5 follicles measuring over 16mm. My husband and I feel like we are comfortable continuing iui with 4 or less mature follicles but not 5. Is estradiol or size a better indicator of egg maturity? Our numbers don’t match up!
Thanks,
Kait
It is usually 150g per follicle of >15mm. So an E2 of 750 could be compatible with 6 follicles.US dimensions are better than [E2] but a combination of both parameters is best.
Intrauterine insemination (IUI), the injection of sperm into the uterus by means of a catheter directed through the cervix, has been practiced for many years. The premise of this procedure is that sperm can reach and fertilize the egg more easily if placed directly into the uterine cavity. IUI is a procedure that bypasses the cervix and places specially prepared sperm into a woman’s uterus around the time of natural or induced ovulation. The suggested advantage of IUI is that it shortens the path that sperm would normally take to a woman’s fallopian tubes.
In the early ‘60s, physicians were injecting small quantities of raw, untreated semen, (sperm plus the seminal plasma) directly into the uterus at the time of expected ovulation. However, when more than 0.2 ml of semen was injected in to the uterus, serious and sometimes life endangering shock-like reactions often occurred. It was subsequently identified that the reason for such reactions related to the presence of prostaglandins within the seminal plasma. This led to the practice of injecting small amounts (less than 0.2 ml) of raw semen. However, the pregnancy rates were dismal and side effects, such as severe cramping and infection were rampant.
Soon after establishing the Northern Nevada Fertility Center in Reno in 1982 (the Nation’s first private in vitro fertilization (IVF program), we began to recognize the potential advantage of washing and centrifuging raw semen, so as to separate sperm from the seminal fluid, and thereby remove prostaglandins that cause most of the problems. We subsequently introduced and, thereupon, became the first to publish on intrauterine insemination (IUI) in the Journal, Fertility and Sterility (April 1984).
Indications for Intrauterine Insemination (IUI)
•Artificial insemination using frozen (donor) sperm: The recognition of HIV infection as a sexually transmitted disease, coupled with the fact that the virus is present in semen months before it can be detected in the blood, mandates that all donors have their semen cryopreserved (frozen) and stored for at least six months, whereupon, they be re-tested for HIV infection. Only upon confirmation of a negative test should the cryopreserved semen specimen be thawed and used for insemination. Since cryopreservation inevitably reduces sperm motility and function, it is not adequate to simply thaw the frozen specimen and then inseminate the raw semen into the vagina. Rather, the semen specimen should be processed for IUI. Provided that the recipient is ovulating normally, there is no need to administer fertility drugs, such as Clomiphene, Pergonal, etc.
•Artificial insemination with partner’s sperm: In cases of sexual dysfunction (impotence, retrograde ejaculation, etc.) or timing issues, partner’s sperm may need to be collected and processed in preparation of IUI.
•Cervical mucus hostility: Sometimes the cervical mucus acts as a barrier to the activation and passage of sperm as it passes through the cervical canal. Such hostility may be due to poor physical qualities of the mucus, cervical infection, or the presence of antisperm antibodies. In all but the latter situations, IUI can readily be performed during natural cycles, unless the woman has ovulation dysfunction. However, when infertility results from the presence of antibodies in the cervical mucus, IUI will likely be ineffectual and should be replaced by in vitro fertilization (IV).
•Absent or dysfunctional ovulation: In some cases where the woman requires the use of fertility drugs to induce normal ovulation, the concomitant performance of IUI might improve pregnancy rates.
Selecting the Fertility Drugs for Intrauterine Insemination (IUI)
Clomiphene citrate (Serophene, Clomid): Clomiphene citrate is taken orally for 5 days starting on day 2 to 5 of the menstrual cycle. Ovulation will usually occur 10 days later. In some cases, hCG is used to trigger the ovulation but this is often unnecessary. Clomiphene is a relatively inexpensive and safe method for inducing ovulation and this is why it is so commonly prescribed to women undergoing IUI. However, women receiving clomiphene have about a one third lower pregnancy rate per cycle than is the case using injectible fertility drugs. but it there are draw-backs. Here are a few reasons why this is so:
1)Clomiphene citrate is an anti-estrogen. .Ordinarily normally ovulating women (without exposure to clomiphene) produce a single dominant follicle which produces enough estrogen to promote optimal cervical mucous production and an adequate endometrial lining (>9mm) However, with clomiphene is used to induce ovulation, its anti-estrogenic effect blunts this response. In fact on clomiphene,it requires much more estrogen to override this effect such that unless at least 3 large follicles develop so as to allow the blood estradiol levels to rise above 400pg/ml, cervical mucus production and endometrial development will usually be insufficient to allow a healthy pregnancy to occur. Younger women with normal ovarian reserve (Day-3 FSH of <9miu/ml) will usually produce >3 follicles where as women over 40 years of age and those (regardless of age) with diminished ovarian reserve will rarely do so and thus are very unlikely to achieve viable pregnancies on clomiphene
2)Clomiphene induction of ovulation is associated with a 15-20% chance of a condition called luteinized unruptured follicle (LUF) syndrome where the hormonal changes that precede and accompany and follow ovulation (including a rise in blood progesterone level) occur but this happens without ovulation occurring .LUF syndrome thus leads to the erroneous conclusion that an egg has been released when, in fact, it remains “trapped” in the ovarian follicle.
3)More than 3 consecutive (back to back) of clomiphene will result in a very significant increase in the anti-estrogen effects (referred to in 1&2 above), such that unless a break of at least 1 full menstrual cycle is taken, the likelihood of a viable pregnancy declines to less than 10%, regardless of the woman’s age or her ovarian reserve.
4)Increased production of Luteinizing Hormone: Clomiphene causes the pituitary gland to produce increased amounts of FSH and LH. FSH promotes follicle growth development while excess LH causes the ovary to produce male hormones such as testosterone. While a little testosterone is indispensable to follicle and egg development, too much testosterone can have the reverse effect and harm egg development. This effect is even more deleterious in women with diminished ovarian reserve (elevated FSH levels) and those over 40 whose ovaries tend to produce more testosterone-like hormones.
The following additional factors must be considered when it comes to the use of Clomiphene:
1)It is best not being prescribed for more than three consecutive months in a row to anyone and certainly not without taking a full cycle break before restarting a fourth cycle of treatment. The reason is that after the 3-4 consecutive months of clomiphene therapy, the anti-estrogenic properties are compounded to the effect of virtually converting it to an anti-fertility drug. This explains why >80% of successful clomiphene pregnancies occur within the first 3 months of treatment, and why the vast majority of clomiphene pregnancies that occur after >3 consecutive (back-to-back) cycles of treatment are lost (usually due to early miscarriages).
2)Clomiphene should not be used in women that have diminished ovarian reserve (e.g. women with elevated FSH levels) or in women over 40 years of age.
The good news is that upon discontinuation of Clomiphene for 4-6 weeks, adverse effects disappear, leaving the slate clean.
The real benefit of clomiphene lies in its oral route of administration, low incidence of side effects, and its low cost. The birth rate per clomiphene IUI is about 7-10% per cycle of treatment (about 1/3 lower than when injectible fertility drugs are used.
Letrozole(Femara): Letrozole, like clomiphene is an oral agent induces ovulation that causes the pituitary gland to release large amounts of FSH as well as LH. The advantage that Letrozole has over clomiphene is that unlike the latter, it is NOT anti-estrogenic and thus does not compromise development of the uterine lining or adversely affect the production of cervical mucus. However as is the case with clomiphene, Letrozole causes increased LH release that can lead to overproduction of male hormones (e.g. testosterone) by the ovaries with potentially adverse effect on egg/embryo quality.
Thus while Letrozole does have potential advantages over clomiphene, the exaggerated LH-induced testosterone effect, especially in women over 40 years of age and/or those with evidence of diminished ovarian reserve limits its value.
Gonadotropins (Menopur, Gonal-f, Folistim and Puregon:) Women with absent or abnormal ovulation who require fertility drugs in preparation for IUI should receive gonadotropins. Granted, these agents are more expensive than clomiphene, but they have no anti-estrogenic properties.
The birth rate with gonadotropin IUI in women under 35 years of age (in the absence of male infertility, where it is much lower) is about 10-15%. However, success is affected by, and contingent upon, the procedure being performed (1) for the correct indications, (2) avoiding the performance of IUI when contraindications exist (see below) and, (3) where the woman is ovulating normally on her own. Success rates decrease as a woman’s age advances. In women 35-40 years of age the birth rate is 5-10% per cycle and for over 40 years, the birth rate per cycle is under 2%, declining to less than 1% after age 43.
Relative Contraindications to Intrauterine Insemination (IUI)
Advancing age: A woman’s natural ability to conceive declines with age starting after age 30. It falls more rapidly after age 35 and then, precipitously so after 40. The main reason for this is that the percentage of eggs that become chromosomally abnormal (aneuploid) through “wear and tear” increases as she gets older, such that by age 40 an ovulated egg is probably 3 times less likely to be able to propagate a viable pregnancy than at age 30. This explains the fact that under 35, the normally ovulating woman who receives injectible fertility drugs to induce ovulation has about a 10-12% chance of having a baby. In comparison, after age 40, the same woman would have about a 2% chance. For this reason alone, IUI is best suited to women under 35 and, in my opinion, should NOT be undertaken after age 40. Ages between 35 and 40 represent a “gray area.”
Significant Male Infertility: Contrary to popular belief, the performance of IUI in cases of male infertility does not improve success rates over regular and well-timed intercourse alone. In vitro fertilization with intracytoplasmic sperm injection (IVF/ICSI) is the only method to optimize pregnancy rates in association with male refractory infertility.
Tubal damage
1.Post-Pelvic Inflammatory Disease (PID): It is very important to understand that Fallopian tubes are not mere “pipes” through which sperm, egg and embryo must pass to achieve an intrauterine pregnancy. They are vital and sophisticated organs that serve intricate functions in the reproductive process. They transport sperm in the direction of the ovary, while at the same time, the fimbriae (petal-like extrusions at the end of the tube) apply themselves to the area of the ovary from which the egg is ovulating in order to pick up the extruding egg, and carry it back down the tube towards the uterus. About one third of the way back, the egg encounters the sperm and fertilization occurs. Thereupon, the resulting embryo is transported to the uterine cavity where it hopefully will implant.
PID, the commonest cause of damaged Fallopian tubes will, unless it is diagnosed and effectively treated very early on, inevitably and permanently disrupt the sophisticated function and continuity of the inner lining of both Fallopian tubes. In more severe cases, the intricate muscular arrangement of the tubal wall is also damaged, compromising the time-sensitive and programmed migration of sperm, egg and embryo. In advanced cases of PID, the fimbria fuse, thus compromising egg pick-up, and ultimately blocking the tube(s) completely.
PID almost always affects both Fallopian tubes. Indeed, one tube might be more damaged than the other, but both will be affected to a greater or lesser degree. That is why, even if one tube remains or is surgically rendered patent, the problem of markedly reduced fertility and the increased risk of a subsequent tubal pregnancy remains an ever present risk and reality. Thus, the use of fertility drugs to induce ovulation, or the use of microsurgery to open Fallopian tubes and free surrounding adhesions are often not curative of infertility. Furthermore, in cases where a pregnancy follows, the result is often a tubal (ectopic) gestation. This also serves to explain the fact that the intrauterine pregnancy rate following ovulation induction (with or without concomitant IUI) is likely to be to be at least 10 times lower in women with PID, and why, when a pregnancy does ensue, it is 10 times more likely to be a tubal (ectopic).
Thus, in women who have had PID, IVF is the only way to safely bypass the “damaged plumbing” and initiate a viable intrauterine pregnancy.
2.Post-Tubal Ligation. In large part, the same holds true following successful reconnection of previously ligated (tied) Fallopian tubes. The reason is that even with successful surgical reestablishment of tubal patency, there is always a degree of shortening of the tube(s) or a degree of damage due to surgical scarring of the inner lining of the tube(s). Even when tubes are normal, the birth rate per IUI cycle is about 10%, and following any form of tubal damage (PID or surgically-induced) the success is 5-10 times lower per IUI cycle (i.e. 1%-2%). Hence, IUI can hardly be justified in such cases, and IVF becomes the only effective and viable option.
Endometriosis:
While the exact cause of endometriosis remains an enigma, it is now apparent that immunologic dysfunction is a significant feature of this disease, and that a toxic environment exists in the pelvis (surrounding the tubes and ovaries) in patients with this condition. As a consequence, ovulation – whether spontaneous or induced by fertility drugs – commits the egg to pass through a toxic pelvic environment in order to reach the sperm waiting in the fallopian tube. This significantly reduces the egg’s fertilization potential. Furthermore, once the fertilized egg reaches the uterus, immunologic factors associated with endometriosis increase the risk of the embryo being rejected before pregnancy can be diagnosed. Such women may experience repeated “mini-miscarriages.”
In spite of these anti-fertility influences, many women with mild endometriosis do in fact conceive on their own, or following ovarian stimulation with fertility drugs. However, for reasons already referred to, the chances of conception are significantly reduced. And if they are ovulating normally on their own, the addition of fertility drugs will afford no additional benefit. Simply put, women in their late 20’s to early 30’s who have the time can anticipate about a 40% chance of conceiving on their own within two or three years (contingent upon their ovulating normally and having a fertile male partner). The occurrence of pregnancy in the latter cases occurs in spite of, rather than due to, such treatment. Such women may consider deferring any invasive treatments in favor of a “wait-and-see” approach. Conversely, women over the age of 35 whose egg quality is inevitably on the decline, IVF offers the only rational approach.
Fertility Drugs and Multiple Births
Normally ovulating women usually develop a number of follicles (fluid filled spaces within the ovary(ies) that contain eggs and produce estrogen) during the first week of the menstrual cycle. All but one (and sometimes two) of the follicles fail to develop to the point of being eligible for ovulation. The process is known as Selection. It is important to recognize that in all normally ovulating women, the one or two follicles selected to ovulate will inevitably be larger than the remaining follicles, regardless of whether the woman is receiving fertility agents such as Clomiphene or gonadotropins (Follistim/Gonal-F/Puregon/Fostimon/Menopur, etc). Simply put, one or two follicles will always show enhanced development over the others, and as soon as these selected follicles ovulate, all the remaining follicles are rendered incapable of following suit. As a result, normally ovulating women no not have a greater incidence of high order multiple pregnancies. In contrast, women who do not ovulate at all, and those who ovulate irregularly or dysfunctional do not have the ability to select one or two dominant follicles for ovulation. As such, following the administration of fertility drugs for ovarian stimulation, numerous follicles may develop at the same rate, and several eggs can be ovulated simultaneously. This translates into a greater chance of pregnancy, but also a greater chance of multiple pregnancies. It is interesting that almost all reported cases of high order multiple pregnancies (greater than twins) following the use of fertility drugs have occurred in women who do not ovulate normally on their own.
It follows that only those women with absent or abnormal ovulation are at-risk for high order multiple pregnancies. They, therefore, need to be counseled regarding the consequences of premature birth and the availability of selective pregnancy reduction towards the end of the third month of pregnancy. Another alternative is to avoid the issue completely by choosing in vitro fertilization (IVF), where the number of potential babies can be limited by the number of embryos transferred to the uterus.
It is indeed unfortunate that fertility treatment has become so regimented that most patients find themselves being ushered through a scripted treatment process. As an example, clomiphene, though favored for its convenience and low cost, does NOT yield the same success as IUI with gonadotropin stimulation. In fact the per-cycle success rate of IUI using clomiphene is about 30% less. Also, women with endometriosis (regardless of severity) have much lower success with IUI (see above). Women over age 40 have such a low success with IUI that they cannot afford the time wasted in the process. Such women need IVF.
For the majority of couples who require an individualized strategic plan of action at an early stage, such an approach is emotionally, physically, and financially draining, leaving them both suspicious and critical of the intent of the medical profession.
The introduction of inexpensive Micro-IVF changes the landscape. In fact, the success rate is three times higher than with IUI. This plus the low the relatively low cost of Micro-IVF (as compared with conventional IVF) is a major advantage of the approach.
______________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.
Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .
PLEASE HELP SPREAD THE WORD ABOUT SFS!
Geoff Sher
Good luck
Dear Dr. Sher
Could you please explain the urgency of estradiol tablets use after frozen embryo transfer?
I do understand why I have to use them before the transfer (to thicken the lining) but after? I am on Progynova tablets 6m per day and than 10 mg per day. Six days before transfer I will be starting
Progesterone pessaries. Is progesterone supplement won’t be enough?
You need both estrogen and progesterone to sustain the pregnancy until the placenta starts producing enough of both by approximately 9-10 weeks.
______________________________________________________
ADDENDUM:
INTRODUCING SHER FRERTILITY SOLUTIONS (SFS)
Hitherto I have personally performed the actual hands-on treatment of all patients who, seeking my involvement, elected to travel to Las Vegas for my care. However, with the launching of Sher-Fertility Solutions (SFS), I will as of March 31st take on a new and expanded consultation role. Rather than having hands-on involvement with IVF procedures I will, through SFS, instead provide fertility consultations (via SKYPE) to the growing number of patients (from >40 countries) with complex Reproductive Dysfunction (RD) who seek access to my input , advice and guidance. In this way I will be able to be involved in overseeing the care, of numerous patients who previously, because they were unable to travel long distances to be treated by me, were unable to gain access to my input.
Anyone wishing to schedule a Skype consultation with me, can do so by: Calling my concierge (Patti Converse) at 1-800-780-7437 for an appointment,enrolling online on my website, http://www.SherIVF.com, or 702-533-2691; or emailing Patti at concierge@SherIVF.com or . sher@sherivf.com .
I was very recently greatly honored in receiving an award by the prestigious; International Association of Top Professionals (IAOTP). For more information, go to the press release on my website, http://www.sherIVF.com .
PLEASE HELP SPREAD THE WORD ABOUT SFS!
Geoff Sher