Of course all the factors you mention and many more are part of the screening process. Also, I advocate that you meet with the surrogate.

IVF surrogacy involves the transfer of one or more embryos into the uterus of a surrogate, who provides a host womb and carries the baby to term, but does not contribute genetically to the baby. Typically, the intended mother provides the eggs and her partner (the intended father) provides the sperm. However, at times eggs and/or sperm may be derived from gamete donors. While ethical, moral, and medico‑legal issues still apply, IVF surrogacy appears to have gained social acceptance. We offer IVF surrogacy as an option at Sher Fertility Solutions (SFS().

Candidates for IVF surrogacy can be divided into two groups: (1) women who are not capable of carrying a pregnancy to full term due to: their uterus having been surgically removed (hysterectomy), disease, or developmental absence of the uterus (from birth) and (2) women who have been advised against undertaking a pregnancy because of systemic illnesses such as diabetes, heart disease, hypertension, etc.

As in preparation for other assisted reproductive techniques, the biological/intended parents, the surrogate and/or donors undergo a thorough clinical, psychological, and laboratory assessment prior to embarking on the process. The purpose is to exclude sexually transmitted diseases that might damage eggs, sperm and embryos, or be carried to the surrogate with embryo transfer. They are also counseled on issues faced by all IVF participants such as the possibility of multiple gestation, miscarriage and ectopic pregnancy.

All legal issues pertaining to custody and the rights of the biological parents and the surrogate should be discussed in detail and the appropriate consent forms completed following full disclosure. We recommend that the surrogate and biological/intended parents get separate legal counsel to avoid any conflict of interest that could arise were one attorney to counsel both parties.

Selecting a Surrogate

Couples with the necessary financial resources will usually retain a surrogacy agency to find a suitable IVF surrogacy candidate. We direct our patients to reputable surrogacy agencies who have access to quality surrogates. Because the surrogate gives birth, it is rarely possible or even realistic for her to remain anonymous.

Since recruiting a gestational surrogate from an agency can be very expensive, many infertile couples who qualify for IVF surrogate parenting solicit the assistance of empathic friends or family members to act as surrogates.

Other couples independently seek surrogates by advertising in the media.

Screening the Surrogate

Once the surrogate has been selected, she will undergo thorough medical and psychological evaluations, including:

1. Cervical cultures and/or blood tests to screen for infection with sexually transmitted bacteria such chlamydia, ureaplasma, gonococcus and syphilis or viruses such as cytomegalic virus, HIV, HTLV, and hepatitis.
2. A variety of blood‑hormone tests, such as the measurement of plasma prolactin and thyroid‑stimulating hormone (TSH) and tests to ensure that the surrogate is immune to the development of rubella (German measles).
3. Physical evaluation
4. Psychological assessment

When friends or family members serve as IVF surrogates they should be be carefully assessed to ascertain whether they might have been coerced to participate. This is especially important when a young family member is being recruited.

The surrogate should also be counseled on issues such as risks and consequences of multiple pregnancies. Such discussions should include agreement on the number of embryos to be transferred and the delicate issue of selective pregnancy reduction , in the event of a high order multiple pregnancy (triplets or greater).

The surrogate should visit with her designated IVF physician who should take her medical history and perform a thorough physical examination. Thereupon she should have a full consultation with the nurse coordinator charged with oversight of her treatment. The coordinator will outline the exact IVF-surrogacy process step by step, will make certain that the surrogate understands that she has full right of access to the clinic staff and that her concerns will be addressed promptly at all times. The surrogate should also be informed that if pregnancy occurs, she will be referred to a qualified obstetrician or perinatologist for prenatal care and delivery.

Once a viable pregnancy is confirmed by ultrasound recognition of a fetal heartbeat (at the 6th-7th week), there is a better than 85% chance that the pregnancy will proceed normally to term. Once the pregnancy has progressed beyond the 12th week, the chance of a healthy baby being born is upward of 95%.

At Sher Fertility Solutions (SFS), depending on the age of the egg provider (under 39 years) and her having normal ovarian reserve, we would anticipate approximately a 40%-50% birthrate every time good quality advanced embryos (expanded blastocysts) are transferred. The birthrate falls with further advancement in the age of the egg provider and with diminishing ovarian reserve. It is important to note that there is no convincing evidence to suggest an increase in the incidence of spontaneous miscarriage or birth defects as a direct result of IVF surrogacy.

If the surrogate’s blood pregnancy tests are negative, treatment with estrogen, progesterone and corticosteroids is discontinued, and she can expect to menstruate within four to 10 days. In the event that the pregnancy test is positive, estrogen, progesterone and steroid therapy are continued till the 10th week of pregnancy.

After the evaluation and counseling of both the couple and the surrogate has been completed, the three parties should meet. And, once all the evaluations have been completed, the intended parents will select a date to begin treatment.

Synchronizing the Cycles of Surrogate and Aspiring Mother

Both the surrogate and the egg provider are placed on monophasic birth control pills (BCP) for 10-25 days. The objective ist to insure that they both start menstruating around the same date so as to launch their cycle of treatment together. Thus the duration that each would remain on the BCP will depend on the desired timing of the start of the IVF treatment cycle. At some point while taking the BCP, both parties will overlapped the BCP with a GnRH agonist (GnRHa) such as Lupron for a period of approximately 2-3 days, whereupon the BCP will be stopped and the Lupron continued. Menstruation will follow (in both) within a few days.

At this point the egg provider begins controlled ovarian stimulation (COS) with gonadotropins while the IVF surrogate commences corticosteroid (dexamethasone or prednisone) therapy and either, twice weekly injections of estradiol valerate (Delestrogen) or daily estradiol skin patches. Blood estradiol measurements are taken twice weekly and the dosage of administered estradiol is adjusted so as to attain a blood estradiol level of between 500 and 1,000pg/ml. Then, as soon as the egg provider (based on hormonal testing and ultrasound follicle assessment) receives the hCG “trigger shot” the surrogate starts receiving daily intramuscular progesterone injections ( while continuing estradiol therapy). In the case of day 3 embryo transfers, this continues for 4 days prior to the embryo transfer and in the case of blastocyst transfers, for 6 days.

Preimplantation Genetic Sampling (PGS) Selection-the Ideal Approach for Gestational Surrogacy

PGS of embryos via next generation gene sequencing (NGS) requires that the woman’s IVF cycle be broken into two parts – the first involving stimulation, egg retrieval, fertilization, and removal of a cell from the embryo for testing. Because CGH testing requires 4-5 weeks to obtain results, the embryos are frozen while the testing is performed on the removed cell. The woman then returns at a later date for her embryo transfer. We call this process “Staggered IVF “. The same approach to ET can be used with gestational surrogacy and the same 60+% birth rate can be anticipated when CGH-normal embryos are transferred. In fact, Staggered IVF lends itself to Gestational Surrogacy because it is possible in this way to completely segregate the ovarian stimulation process from the ET. This allows couples seeking gestational surrogacy to delay identifying and recruiting a surrogate until they are assured of having “competent” embryos available for transfer.

Management and Follow‑up after the Embryo Transfer

Following embryo transfer, the surrogate will be given daily progesterone injections and bi-weekly estradiol valerate injections and/or suppositories in order to sustain an optimal environment for implantation. Approximately 10 days after the embryo transfer, she will undergo a pregnancy test. A positive test indicates that implantation is taking place. In such an event, the hormone injections will be continued for an additional four to six weeks. In the interim, an ultrasound examination will be performed to definitively diagnose a clinical pregnancy. If the test is negative, all hormonal treatment is discontinued, and menstruation will ensue within three to 10 days. If the surrogate does not conceive, the aspiring mother may have her remaining embryos frozen, to be thawed and transferred to the uterus of the surrogate at a later date. If, in spite of both the initial attempt and subsequent transfer of thawed embryos the surrogate does not conceive, the infertile couple may schedule a new cycle of treatment.

Toward the Bioethics of IVF Surrogacy

The determination of ethical guidelines has not kept pace with the exploding growth and development in IVF. However, some leaders in the field are working together, sharing experiences and advice, in an attempt to formulate a code of ethics.

The genetic combination of the male and the female provide two of the essential elements which, along with gestation, are necessary to produce a human being. The two‑out‑of‑three rule basically looks at these three elements: the egg, the sperm, and the gestational component. If at all possible, I recommend that at least two of these three components be contributed by the intended parents. If they can only contribute one, it is important to make every effort not to have the other two contributed by the same person (i.e., the egg provider should not also be the surrogate) as this can cause a variety of problems.

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I would not advise using this embryo!

Human embryo development occurs through a process that encompasses reprogramming, sequential cleavage divisions and mitotic chromosome segregation and embryonic genome activation. Chromosomal abnormalities may arise during germ cell and/or preimplantation embryo development and represents a major cause of early pregnancy loss. More than 15 years ago, we were the first to introduce full embryo karyotyping (identification of all 46 chromosomes) through preimplantation genetic sampling (PGS) as  a method by which to selectively transfer only euploid embryos (i.e. those that have a full component of chromosomes) to the uterus. We subsequently reported on a 2-3-fold improvement in implantation and birth rates as well as a significant reduction in early pregnancy loss, following IVF. Since then PGS has grown dramatically in popularity such that it is now widely used throughout the world.

Many IVF programs that offer PGS/PGT-A services, require that all participating patients consent to all their aneuploid embryos (i.e. those with an irregular quota of chromosomes) be disposed of. However, a  growing  body of evidence  suggests  that following embryo transfer, some aneuploid embryos will in the process of ongoing development,  convert to the euploid state (i.e. “autocorrect”) and then go on to develop into chromosomally normal offspring. In fact, I am personally aware of several such cases having occurred in my own practice. So clearly, summarily discarding all aneuploid embryos as a matter of routine we are sometimes destroying some embryos that might otherwise have “autocorrected” and gone on to develop into normal offspring. Thus, by discarding aneuploid embryos the possibility exists that we could be denying some women the opportunity of having a baby. This creates a major ethical and moral dilemma for those of us that provide the option of PGS/PGT-A to our patients. On the one hand, we strive “to avoid knowingly doing harm” (the Hippocratic Oath) and as such would prefer to avoid or minimize the risk of miscarriage and/or chromosomal birth defects and on the other hand we would not wish to deny patients with aneuploid embryos, the opportunity to have a baby.

The basis for such embryo “autocorrection” lies in the fact that some embryos found through PGS/PGT-A-karyotyping to harbor one or more aneuploid cells (blastomeres) will often also harbor chromosomally normal (euploid) cells (blastomeres). The coexistence of both aneuploid and euploid cells coexisting in the same embryo is referred to as “mosaicism.”

It is against this background, that an ever-increasing number of IVF practitioners, rather than summarily discard PGS-identified aneuploid embryos are now choosing to cryobanking (freeze-store) certain of them, to leave open the possibility of ultimately transferring them to the uterus. In order to best understand the complexity of the factors involved in such decision making, it is essential to understand the causes of embryo aneuploidy of which there are two varieties:

1. Meiotic aneuploidy” results from aberrations in chromosomal numerical configuration that originate in either the egg (most commonly) and/or in sperm, during preconceptual maturational division (meiosis). Since meiosis occurs in the pre-fertilized egg or in and sperm, it follows that when aneuploidy occurs due to defective meiosis, all subsequent cells in the developing embryo/blastocyst/conceptus inevitably will be aneuploid, precluding subsequent “autocorrection”. Meiotic aneuploidy will thus invariably be perpetuated in all the cells of the embryo as they replicate. It is a permanent phenomenon and is irreversible. All embryos so affected are thus fatally damaged. Most will fail to implant and those that do implant will either be lost in early pregnancy or develop into chromosomally defective offspring (e.g. Down syndrome, Edward syndrome, Turner syndrome).
2. Mitotic aneuploidy (“Mosaicism”) occurs when following fertilization and subsequent cell replication (cleavage), some cells (blastomeres) of a meiotically normal (euploid) early embryo mutate and become aneuploid. This is referred to as “mosaicism”. Thereupon, with continued subsequent cell replication (mitosis) the chromosomal make-up (karyotype) of the embryo might either comprise of predominantly aneuploid cells or euploid cells. The subsequent viability or competency of the conceptus will thereupon depend on whether euploid or aneuploid cells predominate. If in such mosaic embryos aneuploid cells predominate, the embryo will be “incompetent”). If (as is frequently the case) euploid cells prevail, the mosaic embryo will likely be “competent” and capable of propagating a normal conceptus.

Since some mitotically aneuploid (“mosaic”) embryos can, and indeed do “autocorrect’ while meiotically aneuploid embryos cannot, it follows that an ability to reliably differentiate between these two varieties of aneuploidy would potentially be of considerable clinical value. The recent introduction of a variety of preimplantation genetic screening (PGS) known as next generation gene sequencing (NGS) has vastly improved the ability to reliably and accurately karyotype embryos and thus to diagnose embryo “mosaicism”.

Most complex aneuploidies are meiotic in origin and will thus almost invariably fail to propagate viable pregnancies. The ability of mosaic embryos to autocorrect is influenced by stage of embryo development in which the diagnosis is made, which chromosomes are affected, whether the aneuploidy involves a single chromosome (simple) or involves 3 or more chromosomes (complex), and the percentage of cells that are aneuploid. Many embryos diagnosed as being mosaic prior to their development into blastocysts (in the cleaved state), subsequently undergo autocorrection to the euploid state (normal numerical chromosomal configuration) as they develop to blastocysts in the Petri dish. This is one reason why “mosaicism” is more commonly detected in early embryos than in blastocysts. Embryos with segmental mosaic aneuploidies, i.e. the addition (duplication) or subtraction (deletion), are also more likely to autocorrect.  Finally, the lower the percentage of mitotically aneuploid (mosaic) cells in the blastocyst the greater the propensity for autocorrection and propagation of chromosomally normal (euploid) offspring. A blastocyst with <30% mosaicism could yield a 30% likelihood of a healthy baby rate with 10-15% miscarriage rate, while with >50% mosaicism the baby rate is roughly halved and the miscarriage rate double.

As stated, the transfer of embryos with autosomal meiotic trisomy, will invariably result in failed implantation, early miscarriage or the birth of a defective child. Those with autosomal mitotic (“mosaic”) trisomies, while having the ability to autocorrect in-utero and result in the birth of a healthy baby can, depending on the percentage of mosaic (mitotically aneuploid) cells present, the number of aneuploid chromosomes and the type of mosaicism (single or segmental) either autocorrect and propagate a normal baby, result in failed implantation, miscarry or cause a birth defect (especially with trisomies 13, 18 or 21). This is why when it comes to giving consideration to transferring trisomic embryos, suspected of being “mosaic”, I advise patients to undergo prenatal genetic testing once pregnant and to be willing to undergo termination of pregnancy in the event of the baby being affected. Conversely, when it comes to meiotic autosomal monosomy, there is almost no chance of a viable pregnancy. in most cases implantation will fail to occur and if it does, the pregnancy will with rare exceptions, miscarry. “Mosaic” (mitotically aneuploid) autosomally monosomic embryos where a chromosome is missing), can and often will “autocorrect” in-utero and propagate a viable pregnancy. It is for this reason that I readily recommend the transfer of such embryos, while still (for safety’s sake) advising prenatal genetic testing in the event that a pregnancy results.

What should be done with “mosaic embryos? While the ability to identify “mosaicism” through karyotyping of embryos has vastly improved, it is far from being absolutely reliable. In fact, I personally have witnessed a number of healthy/normal babies born after the transfer of aneuploid embryos, previously reported on as revealing no evidence of “mosaicism”.  However, the question arises as to which “mosaic” embryos are capable of autocorrecting in-utero and propagating viable pregnancies. Research suggests that that embryos with autosomal monosomy very rarely will propagate viable pregnancies. Thus, it is in my opinion virtually risk-free to transfer embryos with monosomies involving up to two (2) autosomes. The same applies to the transfer of trisomic embryos where up to 2 autosomes are involved. Only here, there is a risk of birth defects (e.g. trisomy 21/18, etc.) and any resulting pregnancies need to be carefully assessed and if needed/desired, be ended. Regardless, it is essential to make full disclosure to the patient (s), and to ensure the completion of a detailed informed consent agreement which would include a commitment by the patient (s) to undergo prenatal genetic testing (amniocentesis/CVS) aimed at excluding a chromosomal defect in the developing baby and/or a willingness to terminate the pregnancy should a serious birth defect be diagnosed. Blastocysts with aneuploidies involving > 2 autosomes  are complex abnormal and should in my opinion, be discarded.

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.

• A Fresh Look at the Indications for IVF
• 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.
• 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.
• Hereditary Clotting Defects (Thrombophilia)
• Blastocyst Embryo Transfers done 5-6 Days Following Fertilization are Fast Replacing Earlier day 2-3 Transfers of Cleaved Embryos.
• Embryo Transfer Procedure: The “Holy Grail in IVF.
• Timing of ET: Transferring Blastocysts on Day 5-6 Post-Fertilization, Rather Than on Day 2-3 as Cleaved Embryos.
• IVF: Approach to Selecting the Best Embryos for Transfer to the Uterus.
• Fresh versus Frozen Embryo Transfers (FET) Enhance IVF Outcome
• Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
• 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 and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.

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ADDENDUM: PLEASE READ!!

INTRODUCING SHER FERTILITY SOLUTIONS (SFS)

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

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

THERE WOULD IN MY OPINION BE NO PROBLEM!

It is primarily the egg (rather than the sperm) that determines the chromosomal integrity (karyotype) of the embryo, the most important determinant of egg/embryo competency”. A “competent” egg is therefore one that has a normal karyotype and has the best potential to propagate a “competent” embryo. In turn, a “competent embryo is one that possesses the highest potential to implant and develop into a normal, healthy, baby.

When it comes to reproductive performance, humans are the least efficient of all mammals. Even in young women under 35y, at best only 2 out of 3 eggs are chromosomally numerically normal (euploid). The remainder will have an irregular number of chromosomes (aneuploid) and are thus “incompetent”. The incidence of egg aneuploidy increases with age such by age 39 years, 3 in 4 are “competent”, and by the mid-forties, at best one in 10 are likely to be aneuploid. The fertilization of an aneuploid egg will inevitably lead to embryo aneuploidy (“incompetence”). As previously stated,   an aneuploid embryo cannot propagate a normal pregnancy

Within 38-42 hours of the initiation of the spontaneous pre-ovulatory luteinizing hormone (LH) surge (and also following administration of the human chorionic gonadotropin (hCG) “trigger” shot, given to induce egg maturation after ovarian stimulation with fertility drugs), the egg embarks on a rapid maturational process that involves halving of its 46 chromosomes to 23. During this process, (known as meiosis) 23 chromosomes are retained within the nucleus of the egg while the remaining 23 chromosomes are expelled in a membrane envelopment, from the egg nucleus. This small structure known as the polar body, comes to lie immediately below the “shell” of the egg (the zona pellucida) and is known as the 1st polar body or PB-1. The sperm, in the process of its maturation also undergoes meiosis divides into two separate functional gametes, each containing 23 chromosomes (half its original number of 46 chromosomes).  With subsequent fertilization, the 23 chromosomes of the egg now fuse with the 23 chromosomes of the mature sperm resulting in the development of an embryo with  46 chromosomes (the normal human genome) comprising a combination of the genetic material from both partners. For the embryo to have exactly 46 chromosomes (the euploid number), both the mature egg and mature spermatozoon must contain exactly 23 chromosomes. Only such euploid embryos are “competent” (capable of developing into healthy babies). Those with an irregular number of chromosomes (aneuploid embryos) are “incompetent” and are incapable of propagating healthy babies. While embryo “incompetence” can result from either egg or sperm aneuploidy, it usually stems from egg aneuploidy. However, in cases of moderate or severe male factor infertility, the sperm’s contribution to aneuploidy of the embryo can be significantly greater.

While embryo ploidy (numerical chromosomal integrity) is not the only determinant of its “competency, it is by far the most important and in fact is a rate-limiting factor in human reproduction. It is causal in the vast majority of cases of “failed nidation which in turn is responsible for most cases of a failed pregnancy (natural or assisted) and causes most sporadic early pregnancy losses (both chemical gestations and miscarriages) as well as  many chromosomal birth defects such as Turner syndrome (X-monosomy ) Down syndrome (trisomy 21) and Edward syndrome (trisomy 18) .

In most cases, embryos that develop too slowly as well as those that grow too fast (i.e. ones that by day 3 post-fertilization comprise fewer than 6 cells or more than 9 cells) and/or embryos that contain cell debris or “fragments” are usually aneuploid and are thus unable to propagate a healthy pregnancy (“incompetent”). Additionally, embryos that fail to survive in culture to the blastocyst stage are also almost always aneuploid/”incompetent”.

At a certain point in the later stage of a woman’s reproductive career, the number of remaining eggs in her ovaries falls below a certain threshold, upon which she is unable to respond optimally to fertility drugs. Often times this is signaled by a rising day 3 basal blood follicle stimulating hormone (FSH) level (>9.0MIU/ml) and a falling blood anti-Mullerian hormone (AMH) level (<2.0ng/ml or <15nmol/L). Such women who have  diminished ovarian reserve (DOR) produce fewer eggs in response to ovarian stimulation. While DOR is most commonly encountered in women over 40 years of age it can and indeed also can occur in much younger women.

A few important (but often overlooked concepts should be considered in this regard:

• Age: It is advancing chronologic age and NOT declining ovarian reserve (as evidenced by abnormal blood AMH or FSH that results in an increased incidence of egg/embryo “incompetence” due to aneuploidy
• The ovaries and developing eggs of women with DOR (regardless of age) are highly susceptible to the adverse effect of excessive Luteinizing Hormone (LH)-induced, ovarian overproduction of male hormones (e,g. testosterone and androstenedione). While a little testosterone produced by the ovary promotes normal follicle growth and orderly egg development excessive testosterone has a converse effect. That is why in older women and those who regardless of their age have DOR (and thus excessive LH bioavailability and increased ovarian testosterone production), the use of ovarian stimulation protocols that fail to down-regulate LH activity prior to initiating ovarian stimulation with gonadotropins, often prejudices egg/embryo quality and IVF outcome.
• Simply stated, while age is certainly the most important factor in determining the incidence of egg/embryo aneuploidy, women with DOR (regardless of their age), are less likely to propagate euploid (competent) eggs/embryos. While virtually nothing can be done to lower the incidence of age related aneuploidy, it is indeed possible to avoid a further decrease in egg/embryo “competency”  by individualizing the protocols of ovarian stimulation used.
• My preferred protocols for women who have relatively normal ovarian reserve:
• The conventional long pituitary down regulation protocol: BCP are commenced early in the cycle and continued for at least 10 days. Starting 3 days before the BCP is to be discontinued, it is overlapped with an agonist such as Lupron 10U daily for three (3) days and continued until menstruation begins (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. Daily Lupron (10U) is continued and an FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is administered daily falong with 37.5U of Menopur (an FSH/LH combination) for 2 days. On the 3^rd day the gonadotropin dosage is reduced by about one half and the dosage of Menopur is increased to 75U daily. Daily ultrasound and blood estradiol measurements are conducted starting on the 7^th or 8^th day of gonadotropin administration and continued until daily ultrasound follicle assessments indicate that most follicles have fully developed. At this point egg maturation is “triggered” using an intramuscular injection of a recombinant hCGr (Ovidrel) 500mcg or urinary derived hCGu (Pregnyl/Profasi/Novarel) 10,000U. And an egg retrieval is scheduled for 36h later.
• The agonist/antagonist conversion protocol (A/ACP): This is essentially the same as the conventional long down regulation protocol (see “a”-as above), except that with the onset of post-BCP menstruation, the agonist is supplanted by daily administration of a GnRH antagonist (e.g. Ganirelix, Cetrotide or Orgalutron) at a dosage of 125-250mcg daily until the day of the “trigger”. When it comes to women who have DOR I favor the use of the A/ACP, adding supplementary human growth hormone (HGH). In cases where the DOR is regarded as severe (AMH=<0.2), I often augment  the AACP protocol by using estrogen priming for 7-9 days prior to or with the commencement of gonadotropin therapy; For this I prescribe E2 skin patches  or intramuscular  estradiol valerate (Delestrogen), prior to or sometimes concurrent with, the  commencement of the GnRH antagonist administration.
• The following Ovarian stimulation protocols are in my opinion best avoided in stimulating olderf women and /or thosed who regardless of age , have  DOR :

1. Microdose agonist (e.g. Lupron) “flare” protocols which result in an out-pouring of pituitary-LH at the critical time that ovarian follicles and eggs start developing/growing.
2. High dosages of LH -containing fertility drugs (e.g. Menopur).
3. Supplementation with preparations that are testosterone-based
4. Supplementation with DHEA (which is converted to testosterone in the ovaries.
5. Clomiphene citrate or Letrozole which cause increased release of LH and thus increase ovarian male hormone (testosterone and androstenedione output.
6. “Triggering” egg maturation using too low a dosage of hCG (e.g. 5,000U rather than 10,000U) or Ovidrel (e.g. 250mcg of Ovidrel rather than 500mcg)
7. “Triggering” women who have DOR, with an agonist (alone)such as Lupron Superfact/ Buserelin/Aminopeptidyl/Decapeptyl.

• Preimplantation Genetic Screening (PGS):

The introduction of preimplantation genetic testing/screening (PGT/PGS) for e permits identification of all the chromosomes in the egg and embryo (full karyotyping) allowing for the  identification of the most “competent” (euploid) embryos for selective transfer to the uterus. This vastly improves the efficiency and success of the IVF process and renders us fare better equipped us to manage older women and those who regardless of their age, have DOR.

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.