Overview

Preimplantation genetic testing is a technique used to identify genetic defects in embryos created through in vitro fertilization (IVF) before pregnancy. Preimplantation genetic diagnosis (PGD) refers specifically to when one or both genetic parents has a known genetic abnormality and testing is performed on an embryo to determine if it also carries a genetic abnormality.

In contrast, preimplantation genetic screening (PGS) refers to techniques where embryos from presumed chromosomally normal genetic parents are screened for aneuploidy.

Because only unaffected embryos are transferred to the uterus for implantation, preimplantation genetic testing provides an alternative to current post conception diagnostic procedures (ie, amniocentesis or chorionic villus sampling), which are frequently followed by the difficult decision of pregnancy termination if results are unfavorable. PGD and PGS are presently the only options available for avoiding a high risk of having a child affected with a genetic disease prior to implantation. It is an attractive means of preventing heritable genetic disease, thereby eliminating the dilemma of pregnancy termination following unfavorable prenatal diagnosis.

PGD is currently available for most known genetic mutations

Indications and Conditions

Indications for Preimplantation Genetic Diagnosis

Preimplantation genetic diagnosis (PGD) is recommended when couples are at risk of transmitting a known genetic abnormality to their children. Only healthy and normal embryos are transferred into the mother’s uterus, thus diminishing the risk of inheriting a genetic abnormality and late pregnancy termination (after positive prenatal diagnosis).

Primary candidates for PGD

These include the following:

Couples with a family history of X-linked disorders (Couples with a family history of X-linked disease have a 25% risk of having an affected embryo [half of male embryos].)

1.X-linked diseases are passed to the child through a mother who is a carrier. They are passed by an abnormal X chromosome and manifest in sons, who do not inherit the normal X chromosome from the father. Because the X chromosome is transmitted to offspring/embryos through the mother, affected fathers have sons who are not affected, but their daughters have a 50% risk of being carriers if the mother is healthy. Sex-linked recessive disorders include hemophilia, fragile X syndrome, most neuromuscular dystrophies (currently, >900 neuromuscular dystrophies are known), and hundreds of other diseases. Sex-linked dominant disorders include Rett syndrome, incontinent pigment, pseudo hyperparathyroidism, and vitamin D–resistant rickets.

2.Chromosomal disorders

chromosomal disorders in which a variety of chromosomal rearrangements, including translocations, inversions, and deletions, can be detected using fluorescent in situ hybridization (FISH). FISH uses telomeric probes specific to the loci site of interest. Some parents may have never achieved a viable pregnancy without using PGD because previous conceptions resulted in chromosomally unbalanced embryos and were spontaneously miscarried. Couples with chromosome translocations, which can cause implantation failure, recurrent pregnancy loss, or mental or physical problems in offspring [4]

3.Carriers of autosomal recessive diseases (For carriers of autosomal recessive diseases, the risk an embryo may be affected is 25%.)

4.Carriers of autosomal dominant diseases (For carriers of autosomal dominant disease, the risk an embryo may be affected is 50%.)

Conditions diagnosed using PGD

PGD should be offered for 3 major groups of disease: (1) sex-linked disorders, (2) single gene defects, and (3) chromosomal disorders.

Indications for Preimplantation Genetic Screening

Most early pregnancy losses can be attributed to aneuploidy. Because only chromosomally normal embryos are transferred into the uterus, the risk of first and second trimester loss is markedly reduced. At present, no specific list of indications for preimplantation genetic screening (PGS) is available.

Primary candidates for PGS can include the following:

1.Women of advanced maternal age:

The risk of aneuploidy in children increases as women age. The chromosomes in the egg are less likely to divide properly, leading to an extra or missing chromosome in the embryo (see Table 1). The rate of aneuploidy in embryos is greater than 20% in mothers aged 35-39 years and is nearly 40% in mothers aged 40 years or older

2.Couples with history of recurrent pregnancy loss:

Recurrent pregnancy loss (RPL) is usually defined as 2 or more consecutive pregnancy losses before 20 weeks’ gestation. The cause is frequently unknown but may be secondary to fetal anomalies or uterine abnormalities. Chromosomal abnormalities are noted in 50-80% of abort uses, [10] and couples with RPL have a higher percentage of aneuploid embryos than patients without RPL.

3.Couples with repeated IVF failure:

Recurrent IVF failure (RIF) is usually defined as 3 or more failed IVF attempts involving high-quality embryos. Evidence suggests that this patient population has a higher number of chromosomally abnormal embryos. [13] However, no study has shown an improvement in pregnancy rate with PGS in patients who have a history of RIF. Although most IVF failures can be accounted for by embryonic aneuploidy, various immunological and uterine factors likely contribute to implantation failure

4.Male partner with severe male factor infertility:

Gonadal failure in men has been linked to the generation of embryos with an increased incidence of inherited and de novo chromosomal abnormalities. Normal fertile men have approximately 3-8% of sperm that are chromosomally abnormal. This risk increases significantly in men with severe infertility (i.e., low sperm count, poor morphology, and poor motility) to approximately 27-74% abnormal spermatozoa. [14] With the introduction of intracytoplasmic sperm injection (ICSI) in assisted reproductive techniques, clinicians have given men with poor sperm quality the opportunity to overcome natural selection and successfully produce a zygote.

Various genetic defects have been found to be associated with male factor infertility. This includes aneuploidy, most commonly Klinefelter syndrome, Robertsonian translocations, Y chromosome microdeletions, androgen receptor mutations, and other autosomal gene mutations (eg, cystic fibrosis transmembrane conductance regulator gene and sex hormone-binding globulin gene mutations). [15] Therefore, a high risk of transmission of genetic mutations to the patient’s offspring is associated with IVF involving ICSI.

These patient populations are at risk of failure with IVF because of a high proportion of aneuploid embryos. PGD is believed to decrease this risk by selecting chromosomally normal embryos that have a higher chance of implantation. The use of PGS/PGD in couples with severe male factor infertility may decrease pregnancy rates but also limits the prevalence of chromosome abnormalities. Data are insufficient to recommend routine genetic screening of all embryos in this group of patients. However, if couples do choose to proceed with PGS/PGD, they should be properly counseled on the decreased chance of conception due to the likely reduced number of normal embryos available to transfer. [16]

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Human leukocyte antigen (HLA) matching

Among the new indications of PGD is preimplantation HLA matching. This technique can be applied to exclude the presence of a genetic disorder but also provide a potential donor for stem cell or bone marrow transplantation to an affected child with recessive diseases, including thalassemia’s or acquired malignancies such as leukemia. This has been previously used to avoid the birth of a child with Fanconi anemia, an autosomal recessive disorder, whose HLA-matched cord blood stem cells were successfully transplanted to cure the affected sibling. [17]

How Do PGD/PGS

Before requesting preimplantation genetic diagnosis (PGD), candidates should consult a geneticist or a genetic counselor to evaluate the risk of transferring their genetic abnormality to their offspring. Tests should be performed to confirm the diagnosis of the affected parent, to pinpoint the genetic change leading to the condition in question, and to ensure that the currently available technology can identify that genetic change in a polar body, cleavage state, or blastocyst embryo biopsy.

In order to have embryos to biopsy for PGD/PGS, patients must undergo in vitro fertilization (IVF). After fertilization of the egg with sperm, embryos are allowed to develop into cleavage-stage embryos. On day 3 after egg retrieval, a single blastomere is removed from the developing embryo for genetic evaluation of the embryo. Genetic evaluation is performed using PCR, FISH, or comparative genomic hybridization (CGH). Nonaffected or normal embryos are then transferred into the uterus for subsequent implantation/pregnancy.

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Biopsy Techniques

We performed a blastocyst-stage embryo biopsy.

Blastocyst biopsy

Blastocyst formation begins on day 5 post-egg retrieval and is defined by the presence of an inner cell mass and the outer cell mass or trophectoderm. At this stage of development, the embryo is formed of more than 100 cells. A hole is breached in the zona pellucida in a similar manner as described for a cleavage-stage embryo biopsy, and cells are removed from the trophectoderm using a fine biopsy pipette. The inner cell mass is left undisturbed. Genetic analysis is performed via FISH or PCR analysis as described below.

A limitation of this procedure is the potential acquisition of cells from the trophectoderm that are not representative of the developing embryo (inner cell mass) due to mosaicism (having multiple different types of cell lines). In addition, genetic/aneuploidy testing is completed approximately 24-48 hours of the embryo biopsy; due to the limited viability of embryos in the laboratory (≤6 d after egg retrieval), many embryos do not survive until the time of embryo transfer. Therefore, biopsied blastocysts must be frozen.

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Identification of sex in X-linked diseases

Recurrent miscarriages caused by parental translocations

PGS/PGD

Disadvantages can give false results between 3-7 percent, showing healthy embryos as unhealthy.

There is a slight possibility that it may damage the embryo.

Even with a successful IVF and PGD procedure, pregnancy is not guaranteed after transfer, and a term or near-term delivery is also not guaranteed.

The diagnostic methodology for a new disease is a time-consuming and expensive process.

A relatively large number of eggs or embryos may be found to be abnormal, thus leaving only a few or no healthy embryos for transfer.

For aneuploidy screening, not all chromosomal or genetic abnormalities can be diagnosed with PGD because only a restricted number of chromosomes can be examined at one time during the course of a single procedure.

Other concerns

To date, there are no reports of increased fetal malformation rates or other identifiable problems in babies born from IVF with PGD/PGS. However, the presentation of other abnormalities later in life as a consequence of the PGD/PGS procedure (biopsy) is possible.

Due to a reduction in the number of chromosomally normal embryos available for embryo transfer, patients should be counseled that IVF with PGD/PGS may result in a lower pregnancy rate than if IVF is performed without PGD/PGS. This is particularly true in patients of advanced maternal age who usually produce few embryos and often of marginal quality that are vulnerable to damage from embryo biopsy.

If both fallopian tubes are damaged or blocked, the egg and sperm cannot find each other. This is called tubal factor infertility, and is basically a mechanical barrier that prevents fertilization. Blocked fallopian tubes prevent natural conception, but in vitro fertilization (IVF) can bypass the tubes.

The extirpative approach to placenta percreta consists of Caesarean hysterectomy and resection of invaded tissues while avoiding removal of the invasive placenta from adherent tissues during the operation. Localization of bladder involvement to its upper posterior wall is associated with less bleeding during surgery.

In the case of extensive placenta accreta, a C-section followed by the surgical removal of the uterus (hysterectomy) might be necessary. This procedure, also called a caesarean hysterectomy, helps prevent the potentially life-threatening blood loss that can occur if there’s an attempt to separate the placenta.

Vaginal surgery refers to cosmetic and reconstructive surgical procedures which can reshape the appearance of and/or tighten the muscles of the vagina. There are many reasons why women opt for vaginal surgery. Some may feel uncomfortable with the way their vagina looks, especially after giving birth.

AESTHETIC GENITAL PLASTIC SURGERY

There are a variety of aesthetic genital plastic surgery operations that may enhance appearance and reduce discomfort. These procedures include labiaplasty, clitoral hood reduction, labia majoraplasty, monsplasty and vaginoplasty.

Patients also sometimes refer to these procedures as female genital cosmetic surgery, vaginal rejuvenation, female genital rejuvenation surgery, vulvovaginal plastic surgery and designer vagina surgery, among other terms.

Aesthetic genital plastic surgery involves many choices. The first and most important is selecting a experienced surgeon you can trust.

External anatomy of the female genitalia

The hair-bearing area over the pubic bone at the upper portion of the female genitalia is called the mons pubis. The hair-bearing outer lips are called the labia majora. The inner lips are called the labia minora. In the upper portion in the center is the clitoral hood, which covers the clitoris in part or entirely. Below the clitoris is the urethra, and below that is the vaginal orifice.

Labiaplasty

The term labiaplasty refers to a procedure that reduces the length of the labia minora. It is the most commonly performed aesthetic genital plastic surgery and it can relieve symptoms women experience from twisting and tugging of the labia.

The goal of the procedure is to reduce the labia minora so that they don’t hang below the hair-bearing labia majora. A labiaplasty may be performed to reduce asymmetry when one is longer than the other, or, more commonly, to reduce the length of both labia so that the labia no longer twist, tug or fall out of a bathing suit.

Labiaplasty can be done under either local anesthesia with oral sedation or under general anesthesia.

The most common type of labiaplasty is the trim procedure, in which the extra tissue is removed and sewn up directly. Next in popularity is the wedge procedure, which maintains a natural border after a pie-shaped piece of tissue has been removed. Extra folds of the clitoral hood can also be reduced at the same time. Closure is usually done with absorbable sutures.

The risks associated with labiaplasty include those of most surgical procedures, including bleeding, hematoma and infection. The most common complication is over-resection. While some women desire an aggressive reduction, this can result in chronic dryness, scarring at or near the vaginal opening and pain with intercourse. Healing problems are more likely to occur with a wedge procedure, particularly if the patient is exposed to substances that cause blood vessels to shrink.

Most patients take a week off from work, during which they can reduce swelling and pain by icing with a cold pack sandwiched between the patient’s underpants and an elastic garment, like Spanx. This can be done “twenty minutes on, twenty minutes off.” The patient can also lie with her bottom elevated to reduce swelling.

Patients can resume wearing tampons or having intercourse after four to six weeks. Trim labiaplasty generally allows for a quicker recovery.

While the most distorting swelling is gone by 6 weeks, residual swelling may take six months to disappear.

Labiaplasty typically results in shorter labia that no longer hang down below the level of the hair-bearing labia majora. Most patients who experienced symptoms from twisting and tugging of their labia generally find relief after surgery.

Clitoral hood reduction

Excess folds of the clitoral hood can be reduced with a clitoral hood reduction. The procedure is most commonly done along with a labiaplasty.

The extra folds can create a bulge that is exaggerated when the labia minora are reduced, and a clitoral hood reduction can improve the balance in appearance of the female genitalia.

A clitoral hood reduction is usually done at the time of a labiaplasty under either local anesthesia with oral sedation or under general anesthesia.

There is a risk of bleeding, hematoma, infection, nerve damage, under-resection or over-resection.

Laparoscopic Myomectomy

Myomectomy is a surgical operation to remove uterine myomas (fibroids) without removing the uterus. Myomas are solid, benign (non-cancer) masses that grow in the womb (uterus). Uterine myomas can occur at any age, but oftenly they develop in the reproductive period (between 20-45 years old). Uterine myomas (fibroids) all vary in shape, location and size. They can be a single mass or multiple lumps. Uterine myomas are more common in African black women than Causasian women.

Myomectomy is usually recommended when the patient wants the myomas (fibroids) to be removed but wants to preserve her uterus and fertility. During the myomectomy operation, doctors leave the uterus and reconstruct it by suturing after removing the myomas.

Uterine myomas (fibroids) can cause pelvic pain, infertility, pelvic pressure, heavy bleeding periods, anaemia, back pain, disparonia, miscarriages, urinary frequency or constipation. This procedure is performed under anesthesia in an operating room.

Myomectomy can be done by open surgery, laparoscopically or hysteroscopically. All these procedures are performed in an operating theater and under anesthesia.

During the laparoscopic myomectomy, the abdomen is filled with gas (carbon dioxide) so that  surgeons could see the abdominal organs. After that, the surgeon put a telescopic scope (a tube with camera and light) in your abdomen through very small incisions. The fibroids then removed and taken out from abdomen. After laparoscopic myomectomy, the patient may stay at hospital for one or two nights. After laparoscopic myomectomy, recovery period may take three weeks approximately.

During the hysteroscopic myomectomy, the surgeon removes the fibroids through the vagina and there is no need to make an incision to the abdomen. The surgical method to be chosen (open myomectomy, laparoscopic myomectomy or hysteroscopic myomectomy) depends on the size and location of the myomas (fibroids).

There are a lot of benefits with laparoscopic myomectomy than with open myomectomy, but suturing the uterus after removing the myomas requires a skilled endoscopic surgeon. Laparoscopic myomectomy is one of the most challenging operations in the gynaecologic field.

Compared to open myomectomy, advantages of laparoscopic myomectomy are;

Laparoscopic myomectomy causes less blood loss

Laparoscopic myomectomy has a faster recovery and shorter hospital stay

Less pain after laparoscopic myomectomy compared to open myomectomy

Even though laparoscopic myomectomy is a safe procedure, it is a major surgery. Some of the risks involved in the laparoscopic myomectomy include;

Excessive blood loss

Very rare need for hysterectomy

Very rare chance of the cancer spread when uterine cancer can be mistaken as benign myoma

Embolism and/or thrombosis

Bladder, ureter or bowel injury

Adverse reactions to anesthetic procedure

Abdominal, urinary or wound infection

When performed by an experienced and skilled surgeon, laparoscopic myomectomy is a safe procedure.

Laparoscopy is the most common procedure used to diagnose and remove mild to moderate endometriosis. Instead of using a large abdominal incision, the surgeon inserts a lighted viewing instrument called a laparoscope through a small incision.

A surgical oncologist removes the tumor and nearby tissue during surgery. He or she also performs certain types of biopsies to help diagnose cancer. A radiation oncologist treats cancer .