Our Mission

Patients come first at New Hope.

We understand that the journey to parenthood can be challenging. That's why our staff is dedicated to supporting you through every stage of the journey. We are truly honored that you are considering New Hope Fertility Center. We consider it our duty to provide you with the absolute best patient care possible.

At New Hope Fertility Center, we custom-design our fertility treatments to each individual. Each person's unique fertility plan is designed to ensure that they are receiving the comprehensive care that is right for their body.

New Hope Fertility Center is truly a global leader in the field of human reproductive medicine, bringing together a team of world-class scientists and clinicians committed to providing the best in fertility care -- from maintaining the highest medical and scientific standards, to supporting you through every stage of your journey to parenthood.

Whether you are exploring IVF options or looking to preserve your fertility, New Hope can assist you with your family planning. We are ready to provide you with a full range of both male and female assisted reproduction services.

Warmly,

Dr. John Zhang, MD, MSc, PhD, HCLD
Founder & Director
New Hope Fertility Center

Meet Our Team

John Zhang, M.D., Ph.D.

Dr. Zhang founded New Hope Fertility Center in 2004 after completing his clinical training at NYU. He holds a Ph.D. from Cambridge in IVF and has over two decades of experience in reproductive biology. New Hope has expanded internationally to China, Russia, and Mexico, and Dr. Zhang was named one of New York's Top Doctors in 2011. He is a leading authority in customized, natural, and minimal stimulation fertility care. Read more about Dr. John Zhang.

Mingxue Yang, M.D., Ph.D.

Dr. Yang joined New Hope Fertility Center in 2008, bringing his strong background in molecular biology to the team. With his training in Obstetrics & Gynecology from NYU's School of Medicine, Dr. Yang received an award for Special Excellence in Endoscopic Procedures from the American Association of Gynecologic Laparoscopists. Read more about Dr. Mingxue Yang.

ZiTao Liu, M.D., Ph.D.

Dr. Yang brings a strong background in molecular biology to New Hope. He has received an award for Special Excellence in Endoscopic Procedures from the American Association of Gynecologic Laparoscopists. He actively participates in groundbreaking research, and has been selected as a top OB/GYN in the United States since 2009.Read more about Dr. ZiTao Liu.

Chapter 1

Reproductive Health Overview

Chapter Overview

This chapter provides an introduction to reproductive health of the female and male anatomy, it also reviews many of the common causes of infertility. As you begin your treatment, this chapter will be a useful reference in understanding your body and your treatment protocol.

1.1 The Female Reproductive System

The female reproductive system is a complex system of several organs that produces egg cells and nourishes and protects the developing embryo. Using the diagram below as a guide, familiarize yourself with the main parts of the female reproductive system discussed below.

• The vagina is a musculomembranous canal that is the sexual organ in the female. It extends from the cervix of the uterus to the exterior of the body. The cervix is the narrow opening of the uterus.

Figure 1.1 The Female Reproductive System

• The uterus is a muscular, hollow pear-shaped organ in the lower pelvis that is home to the embryo, which develops into a fetus during pregnancy. Upon fertilization, the egg develops into an embryo. It attaches to and is nourished by the lining of the uterus, the endometrium. The endometrium is composed of mucous membrane influenced by estrogen and progesterone hormones. It grows and becomes thick each month with the capability to support a pregnancy. If pregnancy does not occur, the thickened lining is shed during a process called menstruation.
• The fallopian tubes are 3-4 inch tubes extending from the upper sides of the uterus to just above the ovaries. The tubes form a passageway between the uterus and the ovaries in which the egg and sperm meet and fertilization can occur. Extending from each tube, just above the ovary, are fingerlike projections called the fimbriae, which catch the egg released by the ovary to be drawn up into the tube.
• The ovaries are home to a woman's lifetime reserve of eggs. By the time a female begins her menstrual cycle; her egg reserve has decreased from several million at birth to about 400,000. As a woman ages, her egg reserve continues to diminish and by menopause, her reserve is depleted. During each cycle, several eggs mature in the ovaries in fluid-filled sacs called follicles. Each month, one "dominant follicle" ruptures, releasing a single egg, which is drawn into the fallopian tube for possible fertilization (see Figure 1.2).

Figure 1.2 Structure of the egg: The monthly
"dominant follicle" ruptures releasing a single egg.

1.2 The Menstrual Cycle

The menstrual cycle is a female body's monthly pattern of preparing for a possible pregnancy. The average menstrual cycle is 28 days, though some women may experience shorter or longer cycles. During one menstrual cycle one of the ovaries releases an egg and the uterus grows new endometrium. If the egg is not fertilized by sperm, the endometrium sheds from the uterus in form of a menstrual period through the cervix and vagina.

The menstrual cycle is controlled by an integrated system which involves the hypothalamus, the pituitary, the ovary and the uterus.

The different systems communicate by hormones – a group of different substances that carry the information from one cell to another. The hormonal system involves: release of hormones by the pituitary gland, the brain and the ovaries.

Use Figure 1.3 to guide you through the phases of the menstrual cycle discussed below.

Figure 1.3 The Menstrual Cycle

Follicular Phase

During this phase, the pituitary gland releases follicle stimulating hormone (FSH) which stimulates the growth and development of follicles in the ovaries. As the follicles mature estrogen levels will start to rise and this will have various effects. Ultimately, estrogen will limit itself by signaling the pituitary gland to inhibit FSH production and begin production of luteinizing hormone (LH). In addition to reducing FSH production, estrogen also causes the endometrium to thicken and later be ready of embryo implantation. The spike of LH will trigger the ovulation, which occurs mid-cycle.

Luteal Phase

As LH and FSH spike, the "dominant follicle" ruptures and releases a single egg known as an oocyte. The egg leaves behind the ruptured follicle that shortly thereafter gets filled with blood and forms another functional structure called corpus luteum. The corpus luteum secretes progesterone, which encourages the transformation of the endometrium in preparation for implantation. Meanwhile, the egg travels in one of the fallopian tubes toward the uterus. While in the fallopian tube, the egg may be fertilized by sperm, if sexual intercourse occurred and an adequate amount of sperm is available in the vagina. Once the egg is fertilized, it will continue moving toward the uterus in the form of an embryo and eventually attach to the endometrium.

The corpus luteum lasts only 12-14 days, unless it begins to receive human chorionic gonadotropin (hCG) from the implanted embryo, in which case it remains active for 10 weeks. If pregnancy does not occur, the corpus luteum breaks down, progesterone levels decrease, and the endometrium, which is no longer needed, is expelled through the cervix and vagina. The corpus luteum is replaced by a scar called the corpus albicans.

1.3 Fertilization and Pregnancy

Pregnancy can occur only if the egg encounters sperm within 24 hours of ovulation. After ejaculation, sperm swim from the vagina up through the cervix into the uterus. From the uterus, they make their ascent into both of the fallopian tubes, propelled by their tails and by the contractions of the uterine walls. If ovulation has not occurred when they arrive at the fallopian tubes, they can survive up to three days waiting to encounter and fertilize an egg.

When egg and sperm interact, many sperm attempt to burrow through the outer membrane of the egg called the zona pellucida (see Figure 1.4). When the first sperm is successful, fertilization occurs. The sperm fuses with the egg, transferring its genetic material. The egg then becomes impenetrable to other sperm.

Figure 1.4 Fertilization: Sperm burrowing
through the zona pellucida.

The fertilized egg, now known as an embryo, travels to the uterus and cell division occurs over the course of four days. On day five, the embryo rearranges itself into a hollow ball of cells called a blastocyst. Pregnancy may occurs once the blastocyst or embryo has attached to the endometrium (see Figure 1.5).

Figure 1.5 Pregnancy: Embryo implantation.

1.4 Common Causes of Female Infertility

The most common causes of female infertility include gynecological factors, hormonal dysregulation, sexually transmitted diseases, diet and lifestyle.

• Age: Fertility is greatly influenced by age. After the age of 35, fertility decreases rapidly, and by age 45, the monthly chance of becoming pregnant naturally is approximately 5%.
• Early menopause: The absence of menstruation and the early depletion of ovarian follicles before age 35 can result in infertility. Although the cause is often unknown, immune system diseases, radiation, chemotherapy and smoking are often associated with this condition.
• Elevated prolactin: High levels of prolactin, the hormone that stimulates breast milk production, in women who are not pregnant or nursing can negatively affect ovulation. High levels may result from a pituitary tumor or as a side effect of various drugs.
• Emotional stress: Prolonged emotional stress may interfere with the normal production of FSH and LH hormones required for reproduction.
• Endometriosis: Affecting the function of the entire reproductive system, endometriosis is the growth of uterine tissue outside of the uterus. This tissue responds to the hormonal cycle and grows, sheds and bleeds in sync with the lining of the uterus each month. Endometriosis can lead to inflammation, pelvic pain and infertility.
• Ovulation disorders: Hypothalamic-pituitary disorders can result in low levels of LH and FSH, disrupting normal ovulation.
• Polycystic Ovary Syndrome (PCOS): Is a special form of ovulation disorder with a classic characteristic of polycystic appearing ovaries on ultrasound. In most patients this syndrome goes along with irregular or absent menstrual periods. It is further associated with endocrine anomalies like changes in sugar and fat metabolism. Once normal menses are resumed, the patients should have excellent chances to get pregnant. In addition, patients with PCOS can have excessive reaction to gonadotropins.
• Smoking: The chemical components of cigarettes have been isolated in the fluid surrounding developing oocytes (eggs) and smoking has been shown to cause DNA damage during oocyte cell division.
• Pelvic adhesions: Bands of scar tissue can bind organs after pelvic infection, such as gonorrhea or Chlamydia, appendicitis or abdominal or pelvic surgery and may impact fertility.
• Thyroid disorders: Hyperthyroidism and hypothyroidism can disrupt the menstrual cycle and cause infertility.
• Tubal factors: Scarring in the fallopian tubes can lead to difficulty in the the transport of an oocyte, impeding the sperm from reaching the oocyte, preventing fertilization. If the sperm and the oocyte do meet, it may not be able to travel to the uterus. Such scarring may result from chronic pelvic inflammatory disease. Benign uterine fibroids may also block the fallopian tubes. This often leads to an ectopic pregnancy. Tubal infection may have long term effects on fertility since the risk of ectopic pregnancy increases with each occurrence of tubal infection.
• Weight management: Being over or underweight can disrupt the menstrual cycle, which can interfere with ovulation and hormone regulation. Women who are excessively lean or anorexic can reduce pituitary hormones such as FSH and LH and halt ovulation.
• Other medical conditions: Fertility may be impaired as a result of various health conditions such as autoimmune disorders, sexually transmitted diseases, cancer treatments, diabetes, anemia and irregular shape of reproductive organs such as the uterus.

1.5 The Male Reproductive System

While the male reproductive system is also influenced by hormonal changes, it differs from the female reproductive system in many ways. Unlike women, men produce their sex cells, called sperm, throughout sexual maturity. Additionally, male reproductive organs are both internal and external. Using the diagram (Figure 1.6) as a guide, familiarize yourself with the main parts of the male reproductive system.

• The penis is one of the external parts of the male reproductive system. Other external parts are the testes, which make sperm and secrete the hormone testosterone.
• Sperm are stored and mature in the epididymis, the tissue layer surrounding the testes. The production and maturation of sperm takes approximately 72 hours and sperm remain viable within the epididymis for several months.
• From the epididymis, sperm travel via the vas deferens to a walnut-sized gland called the prostate. The prostate surrounds the urethra and produces prostatic fluid that is added to semen.
• Located above the prostate gland are seminal vesicles, which produce seminal fluid and join the vas deferens at the ejaculatory duct.

Figure 1.6 Male Reproductive System: The male reproductive
system is composed of both external and internal organs.

Figure 1.7 Structure of Sperm: The male
sex cell is produced throughout sexual maturity.

1.6 Common Causes of Male Infertility

A number of factors can contribute to male infertility. These include conditions affecting sperm function, production and delivery, hormonal dysregulation, sexually transmitted diseases, general health and lifestyle factors.

• Age: Though not as marked as in women, a gradual decline in fertility is common after age 35 in men.
• Impaired shape and motility: Abnormal spermatogenesis, or sperm production, may result in sperm that are not able to reach the egg or to penetrate it.
• Low sperm concentration: Normal sperm concentration in men is greater than or equal to 20 million sperm per milliliter of semen. Sperm count lower than 50 percent of this number (10 million) indicates low sperm concentration.
• Varicocele: Varicose veins in the scrotum, called varicocele, may prevent normal cooling of the testicles and lead to reduced sperm count and motility.
• Undescended testicle: This congenital condition occurs when one or both testicles fail to descend from the abdomen into the scrotum during fetal development. When the testicles are exposed to the higher internal body temperature compared to the temperature in the scrotum, sperm production may be affected.
• Testosterone deficiency (male hypogonadism): Disorders of the testicles, or conditions affecting the hypothalamus or pituitary gland in the brain, may result in low testosterone levels that impair fertility.
• Overheating the testicles: Frequent use of saunas or hot tubs can impair sperm production and lower sperm count by raising the core body temperature.
• Genetic defects: Sperm abnormalities may be genetic.
• Sexually transmitted diseases: Repeated bouts of sexually transmitted diseases, such as chlamydia and gonorrhea, can affect sperm motility.
• Sexual issues: Erectile dysfunction, premature ejaculation, painful intercourse and psychological problems can all contribute to infertility.
• Retrograde ejaculation: This occurs when ejaculate does not leave the body during orgasm but rather enters the bladder.
• Blockage of the reproductive system or anatomical irregularities: Blockage of the ejaculatory ducts or various passages through which sperm and ejaculate flow can affect fertility. Men with cystic fibrosis sometimes have a missing or blocked vas deferens, and the lack or misplacement of any part of the reproductive system will often require reconstructive surgery.
• No semen (ejaculate): Men with spinal cord injuries or diseases may not have the ability to produce the fluid required to carry the sperm from the penis into the vagina.
• Anti-sperm antibodies: These antibodies attack sperm and may be present after vasectomy or in the female's body.
• Pesticides and other chemicals: Herbicides and insecticides have been associated with reduced sperm production and testicular cancer. Lead exposure may also cause infertility.
• Malnutrition and weight management: Deficiencies in nutrients such as vitamin C, selenium, zinc and folate may contribute to infertility. Additionally, a high body mass index is associated with impaired fertility in men and women.
• Smoking, alcohol and substance abuse: Use of cocaine or marijuana may temporarily reduce the number and quality of sperm, and smoking tobacco may lower sperm count. Alcohol has also been associated with decreased fertility.
• Cancer treatments: Cancer treatments such as radiation, chemotherapy, and in the case of testicular cancer, the removal of the testicles, can affect fertility.
• Other medical conditions: Fertility may be impaired as a result of various health conditions such as autoimmune disorders, diabetes, thyroid disease, Cushing's syndrome and anemia.

Figure 1.8 Normal and abnormal sperm cells.

Chapter 2

Overview of Common Procedures

Chapter Overview

In the previous chapter, we reviewed the male and female anatomy and common causes of infertility. Currently, an array of advanced procedures and diagnostic tools are available to help correct even the most difficult infertility cases, preserve embryos for future transfer and determine the genetic health of embryos. The following sections will help you become familiar with many of these infertility treatments and procedures.

2.1 Timed Intercourse

Over the course of your menstrual cycle, your core body temperature dips slightly. Your core body temperature is lower during the follicular phase compared to the luteal phase of your cycle, and a sustained shift in temperature (0.4 to 0.6 degrees Fahrenheit) indicates ovulation has occurred. Planning intercourse to sync with this sustained shift in body temperature (when you are most fertile) is called timed intercourse. This can be accomplished by charting your basal body temperature (BBT) which is taken at the same time each morning before getting out of bed.

Your expected ovulation may also be monitored in two to four office visits. These visits consist of hormone levels and sonograms. When ovulation is expected, you will be instructed on the ideal days to engage in sexual intercourse.

2.2 Intrauterine Insemination (IUI)

Intrauterine insemination (IUI), also known as artificial insemination, uses a catheter to place a number of washed sperm directly into the uterus. The purpose is to increase the number of sperm that reach the fallopian tubes and subsequently increase the chance of fertilization. IUI is often selected by couples who have been trying to conceive for at least one year but who have no known reasons for their infertility. It may also be selected for conditions such as low sperm count, decreased sperm mobility, requirement of donor sperm, a hostile cervical condition (such as cervical mucus that is too thick), or sexual dysfunction. Although IUI still requires the sperm to reach and fertilize the egg on its own, it is important to make sure that the sperm is healthy and mobile. IUI provides the sperm an advantage by giving it a head start, but it still has to seek out the egg on its own.

For patients with tubal blockages or damage, ovarian failure, menopause and severe male factor infertility, IUI is not suitable.

The procedure involves stimulating ovulation with medication to encourage multiple egg development, and timing insemination to coincide with ovulation. Semen is collected for insemination after two to three days of abstinence from ejaculation and then "washed" in the laboratory (separating sperm from the naturally accompanying seminal plasma). Washed sperm is then placed into a very thin sterile flexible catheter, which is inserted through the women's cervix and then injected into the uterine cavity (see Figure 2.1).

Figure 2.1 Intrauterine Insemination: Washed
sperm is injected into the uterine cavity.

2.3 In-vitro Fertilization (IVF)

IVF is an assisted reproduction technique in which an egg fertilized outside of a woman's body is transferred into her body. Many IVF treatments involve administering fertility medications to a woman to mature more than one egg in each cycle. Immediately before ovulation, a doctor retrieves the eggs and unites them in the laboratory with sperm either from the patient's partner or a donor. The resulting embryo is then transferred to the woman's uterus for implantation. If successful, pregnancy is confirmed two weeks later with a pregnancy test.

Below is a brief overview of common IVF protocols and their distinguishing features.

Hyper-Stimulation (Conventional) IVF

Conventional IVF protocols are designed to produce a high quantity of eggs by treating patients with multiple daily injections and higher doses of medication as compared to Minimal Stimulation IVF and Natural Cycle IVF.

Minimal Stimulation IVF (Mini-IVF™)

Mini-IVF™ stimulates the ovaries with minimal medication, uses a uniquely thin, flexible needle to retrieve the eggs resulting in briefer, less painful egg retrievals. Also, Mini-IVF™ uses a nasal spray trigger (Synarel) for ovulation induction instead of hCG (human chorionic gonadotropin) which has fewer side effects compared to conventional IVF.

Natural Cycle IVF

Natural Cycle IVF is a drug and chemical-free protocol. It avoids fertility drugs that would otherwise stimulate your ovaries to produce multiple eggs. The underlying principal of this procedure is to capture the single egg your body naturally produces each month during your menstrual cycle.

Donor Egg IVF & Donor Sperm IVF

If your egg or your partner's sperm is not viable for pregnancy, donor eggs and sperm offer an alternative route to having a baby. Donor Egg IVF cycles generally use conventional IVF treatments to maximize the number of eggs that the donor can provide each cycle. Most donor sperm is purchased from frozen sperm banks.

Surrogate IVF

In cases where a surrogate carries your genetically matched child, gestational surrogacy, surrogate IVF is available to retrieve your eggs and fertilize them with sperm from your partner or a donor. The embryos are then implanted into your surrogate's uterus.

2.4 Embryology Techniques

Vitrification (cryopreservation) and embryo banking:

Vitrification is an innovative flash-freezing technique for oocytes, embryos and ovarian tissue. This fertility preservation procedure, which has a 98% survival rate, allows you to store surplus embryos created in one cycle for later use.

Genetic testing

Numerous diseases and disorders classified as chromosomal disorders, single gene defects and sex-linked disorders can be tested for through a technique called pre-implantation genetic diagnosis (PGD).

PGD involves the removal and biopsy of several cells from the embryo when the embryo has reached the blastocyst stage. At the day 3 stage, when the embryo consists of just six to eight cells, a single cell is removed. Biopsies taken at the day 5 stage, when the embryo has about 100 cells, are more indicative. At the day 5 stage, your doctor will remove three or four cells from the trophectoderm, the part of the blastocyst that will become the placenta.

PGD is performed for all single gene defects where the specific mutation is identifiable. Analysis of the cells occurs by fluorescent in situ hybridization (FISH), a diagnostic method used to show the number and arrangement of chromosomes. PGD is an early screening technique and it does not entirely rule out the chance of a defect being present. For this reason, PGD should be followed up with first-trimester screenings.

2.5 Surgical Techniques

As discussed in the previous chapter, infertility can result from a number of mechanical and structural problems with the reproductive system that surgery may be able to correct. Detailed below are some common procedures; a full listing of surgical treatments available at New Hope can be found in the Appendix.

Hysterosalpingogram (HSG)

This radiology procedure is used to examine the inside of the uterus and fallopian tubes and their surrounding environment. A dye is inserted in a thin tube through vagina and into the uterus. Images are taken using a fluoroscope as the dye passes through the uterus and fallopian tubes. The resulting images are used to find any injuries, blockages or anatomical abnormalities.

Hysteroscopy

A hysteroscopy is a procedure used to look at the inside of the uterus. A camera called a hysteroscope is inserted through the vagina into the neck of the uterus and attached to a light source for visualization. This surgical technique allows doctors to view the internal structures of the uterus without the need for an abdominal incision.

Myomectomy

A myomectomy is performed to remove uterine fibroids and reconstruct the uterus. Since the uterus is not removed in its entirety, this presents an alternative to a hysterectomy when suitable.

Ovarian Tissue Transfer

If you are unable to produce viable eggs, ovarian tissue transfer is one donor option you might consider. Tissue transfer involves removing the ovary of one woman, microsurgically dissecting the tissue, and subsequently transplanting it into another woman. It can be a preferable alternative to egg donation because ovarian tissue has potentially thousands of eggs, and the tissue continues to function as a normal healthy ovary in your body long after the transfer.

Testicular Transplant

Testicular transplant is a novel technique for men who have suffered the loss of a testicle. This donor procedure may help restore reproductive capacity. The resulting sperm will have the genetic traits of the donor.

Hysteroscopy

Fibroids

2.6 Intracytoplasmic Sperm Injection (ICSI)

Intracytoplasmic sperm injection is a micromanipulation technique used in cases of male factor infertility where normal sperm quantity and motility is impaired. With ICSI, a single sperm is selected on the basis of its shape and size and then injected into the cytoplasm of a mature egg to achieve fertilization (see Figure 2.2).

Figure 2.2 Intracytoplasmic Sperm Injection: Sperm is
injected into cytoplasm of mature egg.

Assisted Hatching

2.7 Testicular Biopsy

Testicular Biopsy may be helpful to determine the cause of male infertility. The procedure involves examining a tissue sample that contains seminiferous tubules that produce sperm under a microscope. The results may indicate correctable problems with the testis. If the testis is normal, there must be other sources for the infertility. During the procedure, the patient is under local anesthesia.

2.8 Microsurgical Sperm Aspiration

These two procedures are used to retrieve sperm directly from different areas of the testicle. Both procedures are performed under local anesthesia. The sperm can then be used in conjunction with IVF and Intracytoplasmic Sperm Injection (ICSI).

Microsurgical Epididymal Sperm Aspiration (MESA)

This method is used when infertility is caused by blockage. Using an operating microscope, reproductive specialists isolate the epididymis and then retrieve fluid from an epididymal tubule. The fluid obtained is then processed in the laboratory to ensure that sperm are present. Afterwards, the tubules are closed microsurgically. The sperm can then be used immediately or frozen for later use.

Testicular Sperm Extraction (TESE)

This method involves removing a small piece of testicular tissue through an incision in the testes. The tissue is then processed to extract sperm in the laboratory. As opposed to MESA, this process usually results in fewer specimens since they are more difficult to work with and do not freeze as well. TESE is only used in severe cases where it is the only method to deal with poor sperm.

Chapter 3

Mini-IVF™ Step-by-Step

Chapter Overview

The reasons for infertility are varied and sometimes complex, but can often be addressed with the help of an expert team. This chapter provides a step-by-step overview of your Mini-IVF™ treatment starting with the initial consultation. You may find the question and answer section at the end of this chapter helpful, as it reviews common patient questions.

3.1 What to Expect

Vitrification (cryopreservation) and embryo banking:

During the initial consultation, you will meet with your personal care team to discuss your medical history, family goals and design a treatment plan tailored to your needs.

Your comprehensive fertility evaluation begins with a blood test to determine your FSH, estradiol, LH and progesterone levels, as well as a sonogram to determine your antral follicle count (AFC), which help dictate medication and treatment. You will receive routine sonograms to confirm follicular sizes and quantity. Subsequent blood tests and sonograms will aid in timing of the egg retrieval and establish a baseline for your endometrial lining thickness. This baseline will eventually become indicative of the likelihood an embryo will implant on the uterine wall. Sonogram and blood test results ultimately determine when you will begin your treatment cycle and which treatment you will benefit from the most.

Table 3.1 Procedural Overview

3.2 Mini-IVF™ Procedural Overview

Mini-IVF™ stimulates your ovaries with minimal medications (an oral stimulant, such as Clomid, and an injectable combination of FSH and LH hormones) to produce only the best quality eggs your body can mature in one cycle (approximately one to three eggs). The mild nasal spray Synarel is used for ovulation induction, which has a short half-life in the body and does not have the side effect profile common to hCG. The major benefits of the Mini-IVF™ protocol are listed below.

1. Reduces health risks and discomfort often associated with daily drug injections and use of high-dose fertility drugs (see section 3.4).
2. Minimal medication requirement reduces the high cost of drugs.
3. Patients can cycle continuously, eliminating the typical two to three month waiting period between cycles.
4. Facilitates use of only the best quality follicles.

Step by Step Overview

Step 1: Ovarian Stimulation and Cycle Monitoring

On or near day three of your menstrual cycle, you will begin a daily course of an oral stimulant, such as Clomid, as needed, until your follicles have developed sufficiently for ovulation. Some injectable medication may also be necessary depending on your hormonal requirements. Routine sonograms and blood tests will monitor follicular growth progression and ovulation timing.

Figure 3.1 Follicular Growth Progression: Once follicles have
reached the desired size, ovulation will be triggered.

Step 2: Egg Retrieval

Prior to ovulation, once your follicles have reached the desired size and your hormone levels have risen, a trigger will be used to prompt final maturation, approximately 36 hours before egg retrieval. On the day of retrieval, a thin, flexible ultrasound-guided needle will be directed to the ovaries through the vaginal canal for egg collection. Since this protocol uses a small, flexible needle and produces only a few eggs, retrievals are relatively quick and simple. Note: You have the option of local anesthesia or IV sedation. However, most patients choose local anesthesia with an antianxielytic such as valium.

After retrieval you may experience spotting and abdominal tenderness. This is normal and should subside shortly after the procedure. Though the entire retrieval process will last approximately three to ten minutes, please allow a few hours for recovery. Note, on a case-by-case basis, if any of your eggs are not fully matured at the time of retrieval, they may be developed via in-vitro maturation (IVM).

Figure 3.2 Egg Retrieval: An ultrasound-guided needed
will be directed to the ovaries through the vaginal canal.

Step 3: Sperm Collection

Immediately following egg retrieval, sperm is collected from your male partner through ejaculation in preparation for fertilization. If your partner is unavailable the day of your retrieval, he may produce sperm at an earlier time and it will be frozen until needed. Sperm previously obtained from a TESE may be used at this time. Also, if you wish to use a sperm donor, your personal care team can guide you in the process of obtaining donor sperm prior to egg retrieval.

Step 4: Fertilization and Assisted Hatching

In most cases, the sperm is added to your mature egg(s) and fertilized via intracytoplasmic (ICSI) sperm injection. Once fertilized, cell division occurs in the zygote and may be transferred on the second day after fertilization. If the plan is to transfer an embryo into the uterus five days after fertilization, it must "hatch," or escape from the zona pellucida, before it can implant for pregnancy. Thus, all zygotes in our laboratory undergo laser-assisted hatching on the third day after fertilization to enhance implantation as an embryo.

Figure 3.3 Fertilization: Sperm and egg are fertilized.

Step 5: Culturing and Selection

Based on a patient's clinical history, embryos are cultured for up to five days prior to transfer. The culturing process aids in selecting the best quality embryos for transfer, ensuring the viability of the embryo to undergo implantation, gestation and live birth.

Step 6: Embryo Transfer

Embryo transfer only takes a few minutes and requires no incision or medication. In preparation, it is important that you maintain a regular schedule and avoid stress and strenuous exercise.

The embryos are placed in a small amount of fluid and injected gently into the uterus through the cervix with a long, thin catheter. The transfer feels similar to a pap smear and requires no anesthesia, though you may experience minor cramping following the transfer. Post-transfer, embryo implantation generally requires two to five days.

Since New Hope promotes a single-zygote/embryo transfer policy, you can choose to freeze surplus embryos using our vitrification freezing method to be placed in your personal embryo bank.

Figure 3.4 Embryo Transfer: Embryos are injected into the uterus.

Step 7: Confirmation

A pregnancy test performed seven to twelve days following transfer will confirm whether the embryo has successfully implanted. An ultrasound, typically performed three weeks after a positive pregnancy blood test, will confirm pregnancy.

3.3 Potential Risks and Side Effects

While gentle protocols like Mini-IVF™ offer significantly lower risks and fewer side effects when compared to conventional IVF, any prescribed medications may have side effects and can pose a risk to your health. To best manage these risks, it helps to be informed. Please carefully review the potential risks and medication side effects below and discuss any questions or concerns with your personal care team.

Potential Risks

Ovarian Hyper Stimulation Syndrome (OHSS)

Ovarian Hyper Stimulation Syndrome is the most common risk associated with conventional IVF, although very uncommon, it can also occur in minimal stimulation cycles. During ovarian stimulation, the maturation of a large number of follicles within the ovary can cause the ovary to swell. As the follicles grow, the eggs inside are surrounded by fluid. When many eggs are retrieved, fluid can accumulate in the abdomen or the chest, requiring hospitalization. Vomiting, diarrhea and shortness of breath are symptoms of severe OHSS, but discomfort and ovarian tenderness are also indicators. If you experience any of these symptoms, contact your doctor immediately.

Multiple Births

Multiple embryo transfers can result in a high-order pregnancy and the health risks to the mother and child are significant. Additionally, the chances of premature delivery increase with higher-order multiples. We advocate single embryo transfer to eliminate the risk of multiple births.

Potential Medication Side Effects

If you experience any of the symptoms or side effects listed below, please contact your doctor immediately.

3.4 Frequently Asked Questions

Below is a list of frequently asked questions. If the following answers do not fully address your questions or concerns, please do not hesitate to contact a member of your personal care team.

Why do some fertility treatments begin with birth control pills?
Birth control pills do not affect a woman's ability to become pregnant once she has discontinued their use. Rather, the medication regulates a woman's cycle to synchronize follicle development prior to ovarian stimulation.

Is there an age limit for Mini IVF™?
We do not have an age limit for pre-menopausal women.

If I decide to use a surrogate, are there special considerations?
There are complex legal issues associated with surrogacy that should be first discussed with an attorney who specializes in surrogacy prior to making decisions on treatment.

What percentage of patients choose Mini-IVF™?
Ninety-five percent of our patients choose this protocol.

Who is a candidate for Mini-IVF™?
Mini-IVF™ is suitable for all pre-menopausal women even if they have responded poorly to previous conventional IVF attempts.

Can stress or changes to my normal routine affect the treatment process?
Yes. It is necessary to reduce stress and changes to your daily routine during the entire treatment process.

Why does Mini-IVF™ require fewer hormones?
Exposure to high doses of hormones can mature a large quantity of eggs at the expense of egg quality. Lower hormone dosages help the body produce only the best quality eggs a woman can mature in one cycle to produce a healthy baby.

How long will I take medications before egg retrieval?
Most women take medication for nine to 13 days.

Will all my retrieved eggs be transferred?
The number of eggs retrieved is not necessarily the number of embryos viable for transfer.

What is Comparative Genomic Hybridization (CGH)?
CGH is used to detect genetic abnormalities in eggs and embryos. Specifically, CGH is used to analyze the copy number changes in DNA to identify abnormal regions in the genome.

Does New Hope perform multiple embryo transfers?
At New Hope, we promote single-embryo transfers to reduce the risks associated with multiple births. Surplus embryos can be frozen using our vitrification method and stored in your personal embryo bank for later use.

Clomid has been used since the 1980s. Are newer and more efficacious drugs available in place of Clomid?
Clomid remains the most prescribed fertility drug worldwide and is considered the first line in infertility treatment medication.

Are Clomid success rates better today compared to when it was first introduced?
Clomid success rates have improved markedly due to technical advances in the field of assisted reproduction.

How often can I take a course of Clomid?
We generally allow patients to use Clomid for five to ten cycles.

Can women over 35 use Clomid or is more aggressive hormone therapy required?
Women over 35 do very well with natural and low stimulation cycles using Clomid. These women generally produce higher FSH in response to Clomid because they have a smaller ovarian reserve than younger women and therefore do not usually require the FSH injections used in conventional therapy.

Why does Mini-IVF™ use Synarel instead of HCG?
HCG has a long half-life, causing the stimulation of immature follicles which can lead to cyst formation in subsequent treatment cycles. Synarel, alternatively, is strong enough to induce ovulation of larger follicles, but has a very short half-life. This preserves smaller follicles for future cycles, rather than stimulating them prematurely. As a result, the chances of healthy egg production are increased and women can cycle continuously. Synarel is especially advantageous for older patients with a limited ovarian reserve.

How do you know I will not ovulate prior to retrieval?
During your menstrual cycle, an estrogen sensor activates the hypothalamus to trigger an LH surge, which induces final maturation when the lead follicle reaches its optimal size. Clomid causes the body to think estrogen levels are low, which results in the release of FSH and LH. These hormones ultimately stimulate follicular production and the release of mature eggs. Over time, though, Clomid acts to block the production of LH, which helps reduce the chances of premature ovulation.

Why is injectable FSH recommended for some women undergoing Mini-IVF™?
Often, patients with a very low baseline FSH cannot produce enough of the hormone with Clomid and require additional FSH to aid follicular development.

Do fertility drugs cause cysts?
Sometimes an immature follicle can evolve into a cyst in the following cycle. In particular, HCG injections can facilitate cyst formation. The presence of a cyst does not necessarily mean you cannot begin another cycle. We minimize the risk of cyst formation by using Synarel as a trigger instead of HCG.

What happens if I do not become pregnant?
If your treatment is not successful, your personal care team will meet with you to discuss your options.

Chapter 4

Patient Resources

Preparing for your fertility treatment can be stressful, both emotionally and financially. This chapter serves as a place to find answers to all those last minute questions concerning your fertility treatment plan.

4.1 Fertility Preservation and Cancer Patients

Your Personal Care Team at New Hope will work with you and your oncology team to coordinate care and design a tailored treatment plan. Many of the fertility treatments outlined in this handbook are available to patients who are survivors of various types of cancer or are looking to preserve their fertility prior to undergoing cancer treatment.

New Hope offers gentle stimulation techniques to aid in fertility preservation through oocyte or embryo cryopreservation. From the start of stimulation to banking, the process usually lasts three to four weeks and facilitates a speedy return to all other necessary treatments. A combination of Femara or Tamoxifen with gonadotropin injections has proven safe and effective in such protocols (drug information below).

We require the approval of your treating oncologist and ask that you provide all medical records pertaining to your cancer treatment including surgical and biopsy reports, as well as pathology reports and any tumor marker tests.

4.2 Out of Town Patients

As an out-of-town patient, below are some important factors to consider prior to starting treatment.

Pre-Screening Tests

The provided IVF Checklist for Pre-Screening Testing lists all infectious disease and genetic screening tests that must be completed prior to starting an IVF cycle. If any of the required medical testing is performed outside of our facility, please fax us all medical records and test results. All infectious disease tests must be completed within one year from the date you start your IVF cycle at New Hope. If pre-screening tests were completed more than one year ago, they are invalid and will need to be re-administered before your IVF cycle can begin. Genetic screening tests are accepted regardless of the date performed. IVF screening test results will determine the candidacy of you and your partner.

Consent Forms

All consent forms must be read prior to your visit to New Hope and are available online for your review at www.newhopefertility.com, by clicking "New Patient." On the day of your appointment at New Hope, a nurse will assist you in completing all consent forms and witness you and your partner's signature(s).

Financial Considerations

You must contact our Financial Department prior to the start of your IVF cycle. Financial Coordinators are available Monday through Friday between 9 a.m. and 5 p.m. EST.

Monitoring

If you are on the first day of your period or are to schedule a monitoring visit, please call and inform our clinical staff that you are an out of town monitoring patient and need orders for your local clinic. Physician orders for the first monitoring visit will then be sent to your local clinic. This ensures all correct testing is performed and that results will be sent directly to our clinic. It is also necessary to find a local clinic or hospital that can perform "same day" results on hormone levels so you can receive detailed instructions immediately following the review of results for each monitoring visit. Finally, please be mindful of coordinating office hours and whether weekend monitoring is possible when choosing a local clinic.

Please be sure to call our office by 3 p.m. EST each monitoring day if you have not received a call from your Personal Care Team with instructions. This may mean that we have not received the day's results and will need to follow up with your clinic. Also, please inform our clinical staff of your preferred pharmacy, their contact information and business hours.

Retrieval

On the day of your egg retrieval, if your plan is to fertilize the oocytes retrieved, a semen specimen must be available. If the sperm is fresh, your spouse/partner will be asked to produce a semen specimen. If the sperm is frozen, whether from a spouse/partner or donor, it must be at New Hope prior to the egg retrieval.

If you have any questions regarding semen analysis, semen collection or sperm freezing/storage or transporting frozen sperm vials, please call and speak with someone in our Andrology Laboratory prior to starting your IVF cycle.

As you approach the date of your egg retrieval, we recommend that you and your spouse/partner begin preparations for the trip to our office in New York. Your Personal Care team will help you coordinate scheduling to ensure you arrive to New York on time.

4.3 Financial Considerations

As part of your Personal Care Team, a Financial Coordinator is available to discuss all concerns about financing your treatment. However, since each person receives an individualized treatment plan, you will receive your plan and pricing information during the initial consultation. If applicable, prior to your initial consultation, we will contact your insurance provider to get a comprehensive understanding of your fertility coverage and when necessary, obtain all required pre-authorizations and file all in-network claims paperwork on your behalf.

During the initial consultation, your Financial Coordinator will also schedule payment for all fees not covered by your insurance, co-pays, out of network charges and deductibles. All fees must be paid in full prior to starting your treatment course. We accept cash, money orders and most major credit cards.

4.4 Information Disclaimer

Medical information published for New Hope Fertility Center is strictly for informational purposes and does not replace or preclude medical advice provided by licensed health care professionals. While special consideration has been made to ensure correctness, currency and completeness, errors are possible and the medical field is dynamic. The reader assumes full and sole responsibility for any action taken based on information provided in this handbook. All information should be carefully reviewed with your health care provider and as such, New Hope Fertility Center is not liable for any explicit, implicit, exceptional or otherwise harmful incidence.

This handbook and all components and elements thereof cannot be reproduced, duplicated, distributed, or modified in any form without New Hope Fertility Center's explicit written permission.

Comments & Concerns

At New Hope, we are committed to providing our patients expert care in a professional and comforting environment. If you have any comments or concerns, please do not hesitate to contact us.

Phone: 212-517-7676
E-mail: info@nhfc.com