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In Vitro Fertilization (IVF)

What is IVF?

In vitro fertilization (IVF) is an assisted reproductive technology that begins by collecting a woman’s eggs and a man’s sperm and combining them together outside the woman’s body in a laboratory dish for fertilization. In vitro is Latin for “in glass” and refers to the laboratory Petri dish in which the egg and sperm are combined. After the eggs are fertilized and become embryos, the physician determines the best embryo(s) to transfer to the woman’s uterus.

If IVF treatment is successful, the embryo will implant in the uterus and result in a pregnancy. Any remaining embryos can be frozen and stored for future use or donated to other couples. In vitro fertilization can overcome most causes of male and female infertility.

IVF has a high rate of success because it allows for a controlled interaction of eggs and sperm. Medications increase the number of mature eggs a woman can produce at a single time. Doctors can evaluate each developed embryo to determine which ones are most likely to result in pregnancy.

While not appropriate for all couples or individuals, IVF offers a high chance of pregnancy in a short period of time.

The first IVF baby was born in 1978. Nearly 40 years later, births from IVF represent more than 1.5 percent of all babies born in the United States, according to SART.

It is a complex technique involving five basic steps:
  1. Superovulation, the process of stimulating a woman to release multiple healthy eggs, as opposed to the single egg a woman normally ovulates.
  2. Egg retrieval and sperm collection.
  3. Insemination and fertilization of the eggs by the sperm.
  4. Embryo development and genetic testing (if needed).
  5. Embryo transfer into a woman’s uterus.
IVF Success

Who should consider in vitro fertilization?

Overall, IVF can help some patients experience pregnancy and parenthood who would otherwise not be able to. This includes women in their late 30s or early 40s (see age related infertility below), women otherwiseMulti-ethnic millenial group of friends taking a selfie photo with mobile phone on rooftop terrasse at sunset struggling to conceive due to ovulatory problems, anatomical issues or male infertility factors, men and women who need donor sperm or eggs, and same-sex couples.

IVF is most commonly recommended for women with nonfunctional or missing fallopian tubes and for men with very poor sperm quality. In some instances, a doctor may first recommend alternative infertility treatments, such as intrauterine insemination (IUI), prior to IVF. However, if these are not successful, IVF is often the next step.

IVF treatment is also beneficial when one or both parents carries potential genetic defects because it allows for preimplantation genetic diagnosis (PGD) or preimplantation genetic screening (PGS) on embryos prior to uterus implantation. PGD  and PGS can help increase the chances of a live birth because these forms of genetic testing can identify embryos with chromosomal and genetic defects. Such defects are a major cause of both failure of an embryo to implant and miscarriage. Embryos identified through PGD or PGS as carrying these conditions are not chosen for implantation.

Common reasons to undergo IVF

  • Age related infertility: A woman’s egg quality diminishes with age. IVF can give an older woman a better chance to conceive by increasing the number of eggs she produces, enhancing selection of good quality eggs, or by allowing her to use donor eggs to create embryos.
  • Recurrent pregnancy loss/miscarriage: Depending upon the underlying issue for recurrent pregnancy loss, IVF may be an effective treatment in helping to begin a successful pregnancy by increasing the number of candidate embryos and possibly using PGD or PGS to enhance successful implantation.
  • Unexplained infertility: One fifth of infertile couples are diagnosed with unexplained infertility, and these couples often achieve pregnancy using IVF.
  • Anovulation: If a woman is not ovulating (anovulation), ovulation-inducing pills often aid in achieving pregnancy. But if she is unable to achieve pregnancy with these conservative measures, IVF can be used, which has very high success rates.
  • Damaged fallopian tubes: If significant tubal damage exists, the only fertility treatment options are surgical repair, which has a low success rate, and bypassing the fallopian tubes using IVF.
  • Male infertility factors: Typically, male infertility factors involve low quantity or quality of sperm. In these cases physicians recommend IVF with intracytoplasmic sperm injection (ICSI).
  • Endometriosis: Endometriosis can cause infertility but can be successfully treated using a combination of surgery and medication. If the first round of surgical or medical treatment fails, IVF is an appropriate next step.
  • Low ovarian reserve: If a woman has a low number of eggs in her ovaries, the IVF process can be used to stimulate healthy eggs to develop, allowing the reproductive endocrinologist to collect mature eggs directly from the ovaries. In particular, younger women with low ovarian reserve who generally have good egg quality would have better success rates with IVF treatment.

What are the risks of IVF?

The most widely reported risk associated with IVF is a multiple birth pregnancy (twins or more). This can result in pregnancy and labor complications, premature delivery, and ongoing medical and developmental problems for the children. Although IVF can be uncomfortable, most women resume normal activities within a day after undergoing treatment.

As with many medical treatments, there is always a risk of negative drug interactions and side effects. Fertility medications can have a number of side effects including headaches, mood swings, abdominal pain, hot flashes and bloating. Considered a surgical procedure, IVF carries the normal risks of surgery including reaction to anesthesia, blood loss, damage to tissue and organs, and infection.

There is also a very small risk that some women will overreact to the hormone drugs used to stimulate the ovaries, but ultrasound and hormone monitoring during this drug treatment phase usually ensures that any overreaction is foreseen and any risk avoided.

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Treatment and Testing

Assisted Hatching
Assisted hatching at a glance
  • Assisted hatching is a technique that helps an embryo break free from its outer shell so it can implant in the uterus for a pregnancy.
  • The procedure uses a laser to artificially rupture the embryo’s zona pellucida (outer shell) during in vitro fertilization (IVF).
  • According to the American Society for Reproductive Medicine (ASRM), assisted hatching can slightly improve chances of embryo implantation in women with poor prognosis and previous failed IVF attempts.
  • Use of assisted hatching is not routinely recommended, and the procedure is debated within the medical community due to potential complications and little proof of increased live-birth rates.
What is assisted hatching?

Assisted hatching involves the artificial breaching of the zona pellucida, or the embryo’s outer shell, as a technique to improve implantation and pregnancy rates following IVF. Since the early 1990s, many assisted reproductive technology programs have incorporated the use of assisted hatching in an effort to improve clinical outcomes.

In order for a pregnancy to occur, a fertilized egg (embryo) must travel from the fallopian tube and implant in the uterus. Before it can implant, an embryo must hatch by breaking through a protein capsule that makes up its outer shell, called the zona pullucida.

Failure to hatch can be due excessive thickness the zona pellucida.

Assisted hatching is typically performed on day three after fertilization. On the day of the embryo transfer, an embryologist carefully evaluates embryos for quality. Depending on their stage of development, an embryologist assists the hatching by making a small nick in the zona pellucida using a laser.

Lab specialists then rinse and incubate the embryos for a few more hours before the embryo transfer to the uterus. This procedure may occasionally increase the chance that an embryo will implant in the uterine wall and facilitate a successful pregnancy.

Fertility specialists do not recommend routine use of assisted hatching. But breaching the zona pellucida with a laser for the purpose of embryo biopsy and preimplantation genetic testing is now a standard of care and is considered very low risk when performed by a trained and experienced embryologist.

Who should seek assisted hatching?

Often IVF failure is due to an embryo’s failure to implant in the uterus. Assisted hatching can improve the chances of implantation during IVF and is considered an option for patients who are able to achieve good fertilization and embryo cell development, but the zona pellucida is excessively thick and they do not conceive.

Assisted hatching slightly improves clinical pregnancy rates, particularly in poor-prognosis patients. Assisted hatching is sometimes recommended for patients with the following:

  • Embryos with thick or irregular zona pellucida, which may restrict the embryo from hatching or “breaking out” in order to attach to the uterine lining.
  • Diminished ovarian reserve, a condition determined before fertility treatments begin in which a woman’s ovary has fewer embryos than normal and the chances of achieving a pregnancy are low.
  • Have experienced previous implantation failures and whose chances of achieving pregnancy may be increased with the help of assisted hatching.
Assisted hatching considerations

Some complications can occur during assisted hatching independent of the IVF treatment itself. There is a small risk the embryo may be damaged by the actual hatching procedure. Some embryos and embryonic cells may also become damaged during the micromanipulation process, which can lead to IVF failure but will not increase the risk of birth defects. In addition, assisted hatching has been associated with a very slightly increased risk of monozygotic (MZ) twin pregnancies, or identical twins. 

Embryo Transfer
Embryo transfer at a glance
  • Embryo transfer occurs during in vitro fertilization (IVF) when a fertility specialist places an embryo created in the laboratory into the woman’s uterus for implantation and pregnancy.
  • Embryos are typically transferred at either three days or five days after fertilization.
  • An elective single embryo transfer (eSET) is sometimes recommended to reduce the risk of a multiple pregnancy (twins or more), due to increased health risks to the mother and child.
  • The procedure for embryo transfer is the same whether embryos are from a fresh cycle or frozen cycle (embryos previously frozen and stored) prior to transfer.
What is an embryo transfer?

An embryo transfer refers to the part of the IVF procedure in which a physician uses an ultrasound to guide a catheter containing the IVF-produced embryo(s) that places the embryo(s) directly into the uterus. The embryo transfer process only takes a few minutes, does not involve anesthesia and only requires a short recovery period.

Embryos develop through multiple stages, often described by the number of days since the egg was retrieved from the woman’s follicle. For example, day one, day two, day three, day four, day five or day six, all occur after day zero, which refers to the date the egg was retrieved and fertilized.

Embryologists will grade embryos and the type of grading depends on the stage of the embryo. For cleavage stage embryos, typically on day three, the number of cells and a grade (A – D) will be assigned. For blastocysts, there will be a number and two letters assigned. The number refers to the amount of expansion of the fluid (the “cyst”) in the blastocyst. The two letters (A – D) that follow refer to the inner cell mass (destined to become the baby) and the trophectoderm (destined to become the placenta), respectively.

Cells from an embryo can also be tested for genetic anomalies prior to an embryo transfer. Scientists have a choice of two genetic tests for embryos. In preimplantation genetic diagnosis (PGD), an embryologist removes a group of cells to test for a specific genetic abnormality, such as cystic fibrosis. Preimplantation genetic screening (PGS) tests for the proper makeup in all chromosome pairs, as missing or additional chromosomes lead to disorders and diseases. An example of such a disorder is Down syndrome, in which there is an extra chromosome in pair number 21.

Blastocyst transfer

A blastocyst transfer involves growing embryos in a lab for five days before transferring them into the uterus. When the embryo has reached the blastocyst stage (day five), it is more fully developed with multiple cells.

At this point the embryo resembles the stage an embryo would naturally be when it enters a uterus for implantation, which increases the chances of achieving a successful pregnancy. However, not all embryos are able to develop to the blastocyst stage.

Studies show that blastocyst transfers result in higher implantation and pregnancy rates as compared with cleavage stage embryos. Blastocyst transfers may be of particular benefit for patients who develop many good quality embryos, who have failed to achieve a pregnancy with a day three transfer in the past, or who have poor quality embryos at day three.

Cleavage stage embryo transfer

A cleavage stage embryo transfer refers to embryos that are transferred at an earlier stage of development when they have fewer cells, typically six to eight, and occurs on day two or three after fertilization.

Cleavage refers to the division of the cells in an early developing embryo. Cleavage stage embryo transfer is a good option for patients who have fewer good quality embryos. Also, transfer on day three is less risky than allowing the embryos to go to day five.

Gamete intrafallopian transfer (GIFT)

Gamete intrafallopian transfer (GIFT) is a rare technique in which a specialist places the mixed sperm and eggs immediately into the fallopian tube using ultrasound guidance, rather than developing the embryo in the laboratory. The only justification for GIFT is for couples who have strong Catholic faith, as this is the assisted reproductive technology allowed by the Vatican.

GIFT is performed by laparoscopy, in which the doctor inserts a thin tube with camera and surgical instruments through the belly button. In order to perform GIFT, a patient must have at least one normal fallopian tube, as documented by an X-ray (hysterosalpingogram test), and the absence of scar tissue on the outside of the tube, as documented by laparoscopy.

Fresh vs. frozen embryo transfers

Transfers can involve either fresh or frozen embryos. A fresh embryo transfer means that the eggs are removed, fertilized to become embryos, cultured for several days in the lab, and then transferred into the uterus. This occurs during one menstrual cycle, and the embryos are never frozen.

A frozen embryo transfer means that good quality embryos resulting from an egg retrieval cycle are frozen for later use. Frozen embryos can be used during the next menstrual cycle or months (or years) in the future.

How many embryos are transferred?

It is important to determine how many embryos will be transferred. This subject is highly debated. According to the American Society for Reproductive Medicine (ARSM), the goal of assisted reproductive medicine is to achieve a single gestation, or a single birth through treatments.

Elective single embryo transfer (eSET) refers to only transferring one embryo in a cycle. The eSET option is usually recommended when patients have a high chance of becoming pregnant on their first embryo transfer cycle – for example, a woman who is under the age of 35 and has good embryo quality and availability.

In other instances, two or more embryos are transferred to increase the chances of achieving a successful pregnancy. However, the transfer of more than one embryo can result in a multiple pregnancy (meaning twins, triplets or more). This could cause serious health risks for both the mother and baby.

Risks include low birth rate, preterm labor or delivery and fetal loss. A high-order multiple pregnancy, in which three or more embryos are implanted, is an undesirable outcome of assisted reproductive technologies. 

The decision as to number of embryos to transfer should be made by the patient and physician and should take into account several factors, including:

  • Quality and quantity of embryos available for transfer.
  • Developmental stage of the embryos at transfer.
  • Age and medical history of the patient, including previous IVF treatment.

While there are minimal risks associated with embryo transfers, there is a risk that none of the embryos will survive in the lab, that embryos may be damaged in the lab, and that embryos will not be suitable for a transfer.

Intracytoplasmic Sperm Injection (ICSI)
Intracytoplasmic sperm injection (ICSI) at a glance
  • ICSI is a laboratory procedure that aids in fertilization during in vitro fertilization (IVF) by injecting a single sperm directly into the cytoplasm of a woman’s egg that has been retrieved from her ovary.
  • ICSI is used for male infertility conditions due to poor sperm quantity, quality or movement, for women whose eggs’ outer shells are too thick, or when previous IVF attempts have failed.
  • According to the American Society for Reproductive Medicine (ASRM), 50 to 80 percent of eggs injected with sperm will successfully fertilize.
What is ICSI?

Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology that may be used in conjunction with IVF. While similar to standard IVF in which a doctor collects eggs and sperm from each partner, the difference is in how fertilization is achieved.

In conventional IVF, the egg and a large number of sperm (about 50,000) are mixed together in a laboratory dish. For many couples, the quantity and quality of sperm required for this process to work is hard to achieve. In these cases, conventional IVF is not a viable option. ICSI however, increases the likelihood of IVF success.

During IVF with ICSI, a man’s semen is prepared by separating the live sperm from dead sperm and other debris in the semen. A laboratory embryologist then uses high-powered magnification to guide a small needle that injects a single, viable sperm through the outer shell (zona pellucida) and into a retrieved egg’s cytoplasm. If fertilization is successful, embryos will develop that can be transferred into the woman’s uterus or frozen for use in a future IVF treatment.

Since very few sperm are required and the ability of the sperm to penetrate the egg is no longer an issue, couples using ICSI have a greater chance of achieving pregnancy than with just IVF alone.

Who should consider ICSI?

ICSI is particularly effective for male factor infertility conditions including:

  • Low quantity of sperm production, inadequate for conventional IVF or intrauterine insemination (IUI).
  • Variable factors of sperm quality, including trouble attaching to the egg.
  • Blockages in male reproductive tracts that keep sperm from releasing.
  • Poor motility (movement), making it difficult for the sperm to move through a woman’s reproductive tract.

In some cases, the outer layer of the woman’s eggs is too thick or hard for a sperm to be able to penetrate it under normal circumstances, a problem that ICSI bypasses. When previous attempts at IVF are unsuccessful, some patients may opt to try ICSI, even if the man’s sperm quality is normal.

Success rates of ICSI

Between 50 to 80 percent of inseminated eggs are successfully fertilized using ICSI. Pregnancy success rates for embryos created using ICSI are the same as with traditional IVF, according to ASRM.

While fertilization rates using ICSI are high, not all fertilized eggs develop into healthy embryos. Factors such as a woman’s age, egg quality and fertilization issues may result in an abnormal embryo.

Risks of ICSI

ICSI is a form of assisted reproductive technology that has been used since the early 1990s. Some research has linked ICSI to a slightly increased risk of:

  • Conceiving a baby with sex chromosome abnormalities or certain genetic defects.
  • Passing on low sperm count to a male child.

These risks are not conclusive, and some may be caused by underlying infertility rather than ICSI itself. Men with very low sperm counts have a higher risk of passing on genetic defects overall, and may be encouraged to pursue preimplantation genetic testing prior to ICSI.

Another risk of ICSI is also a risk of IVF itself – increased chance of multiple births versus natural conception. Multiple births (twins or more) carry a higher risk of complications to both the mother and the babies. This risk can be minimized by carefully controlling the number of embryos transferred to a woman’s uterus. ASRM reports that once fertilization via ICSI occurs, the chance of a multiple pregnancy is the same as for IVF without ICSI.

Fertility Drugs
Fertility drugs at a glance
  • Fertility drugs are the main treatment for women who are infertile due to ovulation disorders and are an integral part of the in vitro fertilization (IVF) process.
  • They are also first-line treatment for couples with unexplained infertility.
  • Fertility drugs are used in IVF to stimulate ovulation and prepare a woman’s uterus for pregnancy.
  • Most medications are taken either orally or via injection.
  • Side effects of fertility drugs are usually mild and most commonly involve skin irritation at the injection site.
How are fertility drugs used during IVF?

Fertility drugs are the main course of treatment for women who are infertile due to ovulation disorders such as irregular menstrual cycles. According to the American Society for Reproductive Medicine (ASRM), about 25 percent of infertile women have problems with ovulation.

Several other types of medications, from aspirin and birth control to antibiotics, are also an important part of IVF. The combination of fertility drugs used in IVF works by increasing the number of eggs that are recruited at one time from the woman’s reserve of eggs.

When a woman ovulates normally, she typically recruits from her ovarian reserve a large number of eggs to develop, but only ovulates one of them. The remaining eggs that do not ovulate are absorbed by the ovary.

Fertility medications “rescue” these eggs to allow them to continue developing. The patient therefore has a greater number of eggs to fertilize. This allows the embryologist to select the very best eggs for fertilization and embryo creation in order to enhance the woman’s chance of pregnancy.

Typically, a patient begins the IVF process by taking a birth control pill to prevent ovulation too early in the treatment cycle. From there, the patient will begin stimulating her ovaries using injectable medications, followed by a trigger shot to release mature eggs prior to retrieval.

Common fertility drugs used during IVF

Numerous types of fertility drugs are used during IVF, some taken orally and others injected. The exact drug and dosage used during IVF depends on a patient’s age, test results and the stimulation protocol prescribed by her physician and IVF coordinator.

Before taking any fertility drugs, patients should always talk with their doctor about other medications they are taking and fertility drug options, including the benefits and risks of each type.

A typical IVF treatment will involve a mix of the following medications:

Gonadotropins

These are injectable hormones used to increase development of a woman’s eggs, follicles (the sac-like structures where eggs mature) and estrogen levels prior to ovulation. Depending on the drugs used, the injections contain either follicle-stimulating hormone (FSH) or both luteinizing hormone (LH) and FSH.

Women will typically take gonadotropins for seven to 12 days. A physician will closely monitor follicle size and estrogen levels to decide if the dosing is adequate or if a woman needs to continue injections.

Side effects of gonadotropins are generally minor but may include discomfort at the injection site, headaches and fatigue.

Human chorionic gonadotropin (hCG)

An injection of hCG is used during IVF to trigger release of the mature egg(s) after a woman’s follicles have developed. Human chorionic gonadotropin is a naturally occurring chemical produced during pregnancy that is similar in function and structure to LH.

Common hCG drugs include Pregnyl, Profasi, A.P.L., Novarel and Ovidrel.

Side effects are rare but may include bloating, fatigue, mood swings or breast tenderness.

Follicle-stimulating hormone (FSH)

FSH spurs the development and growth of eggs in a woman’s ovaries. It is also sometimes used to stimulate sperm production in men. Common FSH drugs include Bravelle, Gonal-F and Follistim.

Gonadotropin releasing hormone (GnRH) analogs (antagonists and agonists)

These medications work by preventing premature ovulation and are typically prescribed in combination with other hormones (FSH and hCG). By delaying ovulation, GnRH analogs increase the chance of a woman producing fertile eggs and prevent the release of eggs before an egg retrieval occurs.

These drugs include Ganirelix Acetate, Antagon (ganirelix), Lupron Depot (leuprolide acetate), and Lupron.

Women undergoing IVF will typically take a GnRH analog drug for at least two weeks before a baseline appointment and starting hCG injections, when ovulation is triggered.

Side effects may include hot flashes, headaches, trouble sleeping, mood swings, and vaginal dryness. Rarer side effects have been reported with long-term use and may include bone loss and decreased breast size.

Doxycycline

This oral antibiotic decreases the chance of a bacterial infection to both partners involved in IVF treatment. Patients take one doxycycline pill twice a day after they begin hCG injections until their prescription is complete.

Doxycycline increases sensitivity to sunlight and anyone taking it should avoid long exposure to the sun for up to two weeks after taking it. Other side effects include diarrhea, sore mouth and genital itching.

Baby aspirin

Studies show that taking aspirin may increase circulation to the uterus and ovaries, preventing blood clots and reducing miscarriages.

Prenatal vitamins and folic acid

Maintaining a healthy level of vitamins prior to and during pregnancy greatly reduces the chance of birth defects. The Centers for Disease Control and Prevention recommends that women begin taking a multivitamin with folic acid at least a month before becoming pregnant.

Risks and side effects of fertility drugs

Aside from the specific risks and side effects for each drug itself, the biggest risk associated with IVF medications is ovarian hyperstimulation (OHSS). This condition, in which a woman’s ovaries are over stimulated by fertility drugs, causes the ovaries to produce hormones that may cause significant side effects. Most cases of OHSS are mild but some patients may experience a severe reaction.

Patients exhibiting any of the following symptoms of OHSS should contact their doctor right away:

  • Severe pelvic pain.
  • Swelling of the hands or legs.
  • Stomach pain and swelling.
  • Shortness of breath.
  • Weight gain.
  • Diarrhea.
  • Nausea or vomiting.
  • Urinating less than normal.

Other rare side effects may occur. Ectopic (tubal) pregnancies happen in 1 to 2 percent of natural pregnancies, and with IVF the rate is slightly increased. Ectopic pregnancies, in which the embryo implants outside the uterus, can be life-threatening and require treatment with medication or surgery.

Some women may experience drug allergy or sensitivity that involve breast tenderness, headaches, mood swings, or skin issues. These often go away shortly after injection or after taking the medication.

IVF Success Rates

View Success Rates on SART

Your path to success is unique

Women & Infants Fertility Center is part of Women & Infants Hospital, which provides excellent care to patients and training to future doctors and providers. Our physicians are both professors and practitioners of medicine who also conduct clinical trials and research, assuring that our treatments are backed by the latest evidence-based medicine.

Our mission is to put patients – and their needs – first. That means we don’t push patients into more expensive treatments as the preferred option. As a rule, we try the least invasive, least expensive treatments first. For instance, in vitro fertilization (IVF) has the statistically highest rate of success of all assisted reproduction technologies (ART) but may initially be more aggressive than needed.

We know that there isn’t a one-size-fits-all treatment. So, instead, we start every treatment plan with a discussion. After a review of medical history and an investigation of symptoms, we work with our patients to understand their infertility diagnosis and choose, together, the treatment that best suits their circumstances and needs.

We define success by helping everyone

In vitro fertilization is often the preferred treatment for many causes of infertility, and we are proud of our IVF success rates. However, you may notice that they are slightly lower than other fertility groups’ rates regionally.

That’s because we don’t withhold IVF as a treatment for patients with more complex cases who may not be the best candidates for success – even if it might lower our statistical success rates.

It is well known that both age and weight impact pregnancy success rates as well as the health of the baby. Women & Infants Fertility Center physicians will do everything possible to work with a patient to optimize her health, recognizing that some patients may not be able to achieve an ideal body weight. Often losing as little as 5 to 10 percent of body weight is sufficient to both enhance fertility and to have a healthy pregnancy.

While we do have an age limitation for IVF using a woman’s own eggs based on success rates, we feel that if there is a reasonable chance of success and it is not excessively risky for a woman to try to become pregnant, she should be given the opportunity to try. We offer the full range of services including the use of donor eggs, donor sperm and gestational carriers depending on the patient’s needs.

For these reasons, patients should not compare one fertility clinic with the next based solely on success rates and numbers.