I published on this 25y ago.

Sher G, Maassarani G, Zouves C, Feinman M, Sohn S, Matzner W, Chong P, Ching W. “The use of Combined Heparin/Aspirin and Immunoglobulin G. Therapy in the Treatment of IVF Patients with Antithyroid Antibodies” Am J Repr Immunol, 1998; 39:223-5.

often advised to first try ovarian stimulation (ovulation Induction) with intrauterine insemination (IUI) ………as if to say that this would be just as likely to result in a baby as would in vitro fertilization (IVF). Nothing could be further from reality It is time to set the record straight. And hence this communication!

Bear in mind that the cost of treatment comprises both financial and emotional components and that it is the cost of having a baby rather than cost of a procedure. Then consider the fact that regardless of her age or the severity of the condition, women with infertility due to endometriosis are several fold more likely to have a baby per treatment cycle of IVF than with IUI. It follows that there is a distinct advantage in doing IVF first, rather than as a last resort.

So then, why is it that ovulation induction with or without IUI is routinely offered proposed preferentially to women with mild to moderately severe endometriosis? Could it in part be due to the fact that most practicing doctors do not provide IVF services but are indeed remunerated for ovarian stimulation and IUI services and are thus economically incentivized to offer IUI as a first line approach? Or is because of the often erroneous belief that the use of fertility drugs will in all cases induce the release (ovulation) of multiple eggs at a time and thereby increase the chance of a pregnancy. The truth however is that while normally ovulating women (the majority of women who have mild to moderately severe endometriosis) respond to ovarian stimulation with fertility drugs by forming multiple follicles, they rarely ovulate > 1 (or at most 2) egg at a time. This is because such women usually only develop a single dominant follicle which upon ovulating leaves the others intact. This is the reason why normally ovulating women who undergo ovulation induction usually will not experience improved pregnancy potential, nor will they have a marked increase in multiple pregnancies. Conversely, non-ovulating women (as well as those with dysfunctional ovulation) who undergo ovulation induction, almost always develop multiple large follicles that tend to ovulate in unison. This increases the potential to conceive along with an increased risk multiple pregnancies.

So let me take a stab at explaining why IVF is more successful than IUI or surgical correction in the treatment of endometriosis-related infertility:

1. The toxic pelvic factor: Endometriosis is a condition where the lining of the uterus (the endometrium) grows outside the uterus. While this process begins early in the reproductive life of a woman, with notable exceptions, it only becomes manifest in the 2ndhalf of her reproductive life. After some time, these deposits bleed and when the blood absorbs it leaves a visible pigment that can be identified upon surgical exposure of the pelvis. Such endometriotic deposits invariably produce and release toxins” into the pelvic secretions that coat the surface of the membrane (the peritoneum) that envelops all abdominal and pelvic organs, including the uterus, tubes and ovaries. These toxins are referred to as “the peritoneal factor”. Following ovulation, the egg(s) must pass from the ovary (ies), through these toxic secretions to reach the sperm lying in wait in the outer part the fallopian tube (s) tube(s) where, the sperm lie in waiting. In the process of going from the ovary(ies) to the Fallopian tube(s) these eggs become exposed to the “peritoneal toxins” which alter s the envelopment of the egg (i.e. zona pellucida) making it much less receptive to being fertilized by sperm. As a consequence, if they are chromosomally normal such eggs are rendered much less likely to be successfully fertilized. Since almost all women with endometriosis have this problem, it is not difficult to understand why they are far less likely to conceive following ovulation (whether natural or induced through ovulation induction). This “toxic peritoneal factor impacts on eggs that are ovulated whether spontaneously (as in natural cycles) or following the use of fertility drugs and serves to explain why the chance of pregnancy is so significantly reduced in normally ovulating women with endometriosis.
2. The Immunologic Factor: About one third of women who have endometriosis will also have an immunologic implantation dysfunction (IID) linked to activation of uterine natural killer cells (NKa).  This will require selective immunotherapy with Intralipid infusions, and/or heparinoids (e.g. Clexane/Lovenox) that is much more effectively implemented in combination with IVF.
3. Surgical treatment of mild to moderate endometriosis does not usually improve pregnancy potential:. The reason is that endometriosis can be considered to be a “work in progress”. New lesions are constantly developing. So it is that for every endometriotic seen there are usually many non-pigmented deposits that are in the process of evolving but are not yet visible to the naked eye and such evolving (non-visible) lesions can also release the same “toxins that compromise fertilization. Accordingly, even after surgical removal of all visible lesions the invisible ones continue to release “toxins” and retain the ability to compromise natural fertilization. It also explains why surgery to remove endometriotic deposits in women with mild to moderate endometriosis usually will fail to significantly improve pregnancy generating potential. In contrast, IVF, by removing eggs from the ovaries prior to ovulation, fertilizing these outside of the body and then transferring the resulting embryo(s) to the uterus, bypasses the toxic pelvic environment and is therefore is the treatment of choice in cases of endometriosis-related infertility.
4. Ovarian Endometriomas: Women, who have advanced endometriosis, often have endometriotic ovarian cysts, known as endometriomas. These cysts contain decomposed menstrual blood that looks like melted chocolate…hence the name “chocolate cysts”. These space occupying lesions can activate ovarian connective tissue (stroma or theca) resulting in an overproduction of male hormones (especially testosterone). An excess of ovarian testosterone can severely compromise follicle and egg development in the affected ovary. Thus there are two reasons for treating endometriomas. The first is to alleviate symptoms and the second is to optimize egg and embryo quality. Conventional treatment of endometriomas involves surgical drainage of the cyst contents with subsequent removal of the cyst wall (usually by laparoscopy), increasing the risk of surgical complications. We recently reported on a new, effective and safe outpatient approach to treating endometriomas in women planning to undergo IVF. We termed the treatment ovarian Sclerotherapy.  The process involves; needle aspiration of the “chocolate colored liquid content of the endometriotic cyst, followed by the injection of 5% tetracycline hydrochloride into the cyst cavity. Such treatment will, more than 75% of the time result in disappearance of the lesion within 6-8 weeks. Ovarian sclerotherapy can be performed under local anesthesia or under conscious sedation. It is a safe and effective alternative to surgery for definitive treatment of recurrent ovarian endometriomas in a select group of patients planning to undergo IVF

 I am not suggesting that all women with infertility-related endometriosis should automatically resort to IVF. Quite to the contrary…. In spite of having reduced fertility potential, many women with mild to moderate endometriosis can and do go on to conceive on their own (without treatment). It is just that the chance of this happening is so is much lower than normal.

IN SUMMARY: For young ovulating women (< 35 years of age ) with endometriosis, who have normal reproductive anatomy and have fertile male partners, expectant treatment is often preferable to IUI or IVF. However, for older women, women who (regardless of their age) have any additional factor (e.g. pelvic adhesions, ovarian endometriomas, male infertility, IID or diminished ovarian reserve-DOR) IVF should be the primary treatment of choice.

I strongly recommend that you visit 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 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!
• 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?
• Endometriosis and Immunologic Implantation Dysfunction (IID) and IVF
• Endometriosis and Infertility: Why IVF Rather than IUI or Surgery Should be the Treatment of Choice.
• Endometriosis and Infertility: The Influence of Age and Severity on Treatment Options
• Early -Endometriosis-related Infertility: Ovulation Induction (with or without Intrauterine Insemination) and Reproductive Surgery Versus IVF
• Treating Ovarian Endometriomas with Sclerotherapy.
• Effect of Advanced Endometriosis with Endometriotic cysts (Endometriomas) on IVF Outcome & Treatment Options.
• Deciding Between Intrauterine Insemination (IUI) and In Vitro Fertilization (IVF).
• Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s &
• Induction of Ovulation with Clomiphene Citrate: Mode of Action, Indications, Benefits, Limitations and Contraindications for its use
• Clomiphene Induction of Ovulation: Its Use and Misuse!

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ADDENDUM: PLEASE READ!!

INTRODUCING SHER FERTILITY SOLUTIONS (SFS)

Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.

If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or,  enroll online on then home-page of my website (www.SherIVF.com). 

PLEASE SPREAD THE WORD ABOUT SFS!

Geoff Sher

Yes! It is likely to cause the functional cyst to absorb by the next period!

An ovarian cyst is any collection of fluid, surrounded by a very thin wall, within an ovary. An ovarian follicle that is larger than 22mm is termed a functional follicular cyst. They are non-malignant (benign) and harmless and in most cases, don’t even cause symptoms, however, in some cases, rapid distention of the cyst , or rupture with bleeding , can lead to sudden and severe pain and in some cases, a disruption in hormone balance leads to vaginal bleeding.

There are 2 varieties of “functional ovarian cysts:

1. Follicle Cysts: In menstruating women, a follicle containing the unfertilized egg will rupture during ovulation. If this does not occur, a follicular cyst of more than 2.5 cm diameter may result. These cysts develop in response to stimulation with follicle stimulating hormone that is either self-produced (by the woman’s own pituitary gland (endogenous) or is induced by agonists (e.g. Lupron/Decapeptyl/Buserelin) that sometimes propagate increased and sustained pituitary FSH release.
2. Corpus luteum cysts: These appear after ovulation or egg retrieval. The corpus luteum is the remnant of the follicle after the ovum has moved to the fallopian tubes. It usually degrades within 5-9 days. A corpus luteum of > 3 cm is regarded as being cystic.

A:Follicular cysts: These lesions have special relevance in women about to undergo controlled ovarian stimulation (COS) with gonadotropins for IVF where they can literally, “throw a spanner in the works”, causing a delay, postponement and sometimes even cancellation of the cycle of treatment.

Functional Ovarian cysts must be distinguished from “non-functional or cystic ovarian tumors”. By definition, “tumors are capable of independent growth.  Thus “cystic ovarian tumors do not develop as a result of exposure to gonadotropin stimulation and it is this feature that distinguishes them from “functional” ovarian cysts.

Aside from sometimes causing pain and dysfunctional uterine bleeding, unruptured follicular cysts are usually relatively non-problematic. As stated above, in some cases, functional “cysts” undergo rapid distention (often as a result of a minor degree of bleeding inside the cyst itself). In such cases the woman will often experience a sharp or aching pain on one or other side of her lower abdomen and/or deep seated pain during intercourse. The cysts may even rupture, causing sudden lower abdominal pain that exacerbates and may even simulate an attack of acute appendicitis or a ruptured ectopic (tubular) pregnancy. While very unpleasant, a ruptured “functional cyst” seldom produces a degree of internal bleeding that warrants surgical intervention. The pain, typically is made worse by movement. It stabilizes within a number of days but subsides progressively to disappear within about four to seven days.

Whenever an ovarian cyst is detected (usually by ultrasound examination), the first consideration should be to determine whether it is a “functional cyst or a “cystic ovarian tumor”. The reason for this is that tumors are subject to a variety of complications such as twisting (torsion), hemorrhage, infection and even malignant change, all of which usually will require surgical intervention.

Gonadotropin releasing hormone agonists (GnRHa) such as Lupron, Buserelin, Nafarelin and Synarel, administered daily, starting a few days prior to menstruation, all elicit an initial and rapid, out-pouring (“surge”) in pituitary LH and FSH release. This “surge” lasts for a day or two. Then as the pituitary reservoir of FSH and LH becomes depleted, the blood FSH and LH levels fall rapidly reaching near undetectable blood levels within a day or two. At the same time, the declining FSH result in a drop in blood E2 concentration leading to a withdrawal bleed (menstruation). The progressive exhaustion of Pituitary FSH/LH along with the decline in blood E2, is referred to as ” down-regulation” The continued daily administration of GnRHa or its replacement (supplanting)  with a GnRH antagonist (e.g. Ganirelix, Cetrotide or Orgalutron) results in blood LH concentrations being sustained at a very low level throughout the ensuing cycle of controlled ovarian hyperstimulation (COH) with gonadotropins, thereby optimizing follicular maturation and promoting E2 induced endometrial proliferation.

Functional follicular cysts resulting from controlled ovarian stimulation (COS), can occur regardless of whether down regulation with GnRHa (Lupron/Buserelin/Decapeptyl) is initiated in cases where the cycle of stimulation is launched with the woman coming off  a BCP or when the agonist is initiated on day 20-23  (the mid luteal phase) of a natural cycle. When this happens it is due to the initial agonist-induced FSH “surge” sometimes so accelerating follicular growth that it leads to the development of one or more “functional follicular cysts”. These cysts release E2 and cause the blood E2 often to remain elevated (>70pg/ml). Depending on the extent of this effect, it sometimes leads to a delay in the onset of menstruation and thus also to deferment in the initiation of COS.

Failure of menstruation to commence within 4-7 days of initiating treatment with GnRHa suggestive of an underlying “functional ovarian cyst” and calls for an ultrasound examination to make the diagnosis. Once diagnosed, depending upon the number and size of cysts detected. There are two therapeutic options:

• Wait for the cyst to absorb spontaneously and for menstruation to ensue: While it at first might seem that this approach of continuing GnRHa therapy in order to cause absorption of the cyst(s) within a week or two might be a good approach , it often has unintended consequences. First there is the real possibility that prolonged uninterrupted GnRHa therapy might blunt subsequent ovarian follicular response to gonadotropin therapy and second, if menstruation does not follow within 10-14 days, the cycle will usually need to be cancelled.
• Immediate needle aspiration of the cyst(s) under local anesthesia. I personally favor needle aspiration, sooner rather than later in such cases. Menstruation will usually follow a successful aspiration within 2-4 days. Upon menstruation a blood E2 level is measured and as soon as it drops below 70pg/ml COS can be initiated.

1. Corpus Luteum cysts: As with follicular cysts, so at times do Corpus Luteum cysts also bleed, distend and cause fain. They often delay onset of spontaneous menstruation by a week or longer (Halban syndrome”.). In isolated cases, internal bleeding within the cyst substance causes pain, rapid enlargement of the lesion and by ultrasound examination reveals local areas of absorption causing it to appear as a “complex” cystic lesion that simulates a tumor, prompting surgical intervention. Sadly, there are countless cases where women have had an entire ovary removed due to this happening.

“Functional ovarian cysts” rarely present as a serious health hazard. In the vast majority of cases they spontaneously resolve within 2-4 weeks while “cystic tumors” will not. Accordingly, the persistence of any ovarian cyst that persists for longer than 4 weeks should raise suspicion of it being a tumor rather than with a “functional cyst”. Since ovarian tumors can be (or become) malignant, all ovarian cysts that persist for longer than 6 weeks (whether occurring in non-pregnant or pregnant women), should be considered for surgical removal and this should be followed by pathological analysis.

Good luck!

Geoff Sher

Please call 646-792–7476 and ask for Bushra Sudal RN. She will be glad to assist you.

I prescribe twice weekly injections of estradiol valerate (Delestrogen). Using this approach, I aim for peak E2 values ranging between 500 and 1000pg/ml!

Good luck!