Testicles (aka. testes, sing. testis) are male sexual glands, are usually present as a pair, oval in shape and produce the male sexual hormone testosterone as well as the sperms (aka. sperm cells or spermatozoa). Testicles reside in scrotum, which is a sac of skin that hangs below the penis. For normal sperm development, the temperature of scrotum and testicles is slightly lower than the body temperature.
Assisted Reproductive Technologies
Couples may be helped by medical professionals to conceive using various technologies known together as Assisted Reproductive Technologies (ARTs). Every couple has a unique need which is assessed together by one or more of their reproductive endocrinologists, embryologists, andrologists and gynecologists.
Intrauterine Inseminations (IUI)
IUI includes introduction of donor or partner’s sperms directly into the uterus. In other rarer methods of artificial insemination, the sperms may also be introduced into the cervix or the fallopian tubes. IUI is indicated for donor sperms, unexplained infertility, endometriosis, mild male factor infertility, or cervical factor infertility.
In Vitro Fertilization (IVF)
- IVF is the most common ART method and includes fertilization of oocytes and subsequent maturation in a controlled environment in the lab, followed by transfer of the blastocyst to the uterus. IVF may be performed on patient or donor oocytes and sperms, subject to regulations. Sperms are usually obtained by masturbation. Multiple oocytes are obtained by artificial hormonal stimulation of the follicles, followed by ultrasound guided aspiration of oocytes from the fallopian tubes.
- IVF may be performed in a few different ways:
- Standard IVF (stIVF)
- Motile sperms are allowed to naturally fertilize the oocyte(s) in a dish in a nutrient rich culture-medium. After 24 hours, granulosa cells are removed, fertilization assessed and the embryos are allowed to mature. At around 5 days of maturation, blastocyst(s) are transferred to the uterus to allow implantation.
- Intracytoplasmic Sperm Injection (ICSI)
- ICSI involves selection of 1 motile sperm by microscopic examination followed by fracture of the sperm tail, and injection of the whole sperm into the oocyte using micromanipulators. The fertilization is similarly assessed to as stIVF, and mature blastocyst(s) are transferred to the uterus to allow implantation.
- Although American Society of Human Reproduction and European Society of Human Embryology recommend use of ICSI for only male-factor infertility and previous stIVF failure, ICSI is one of the most commonly used methods of ART today. After almost 30 years of its invention, there is mounting evidence that ICSI does not provide increased fertilization rates, and may increase the health risks for the offspring.
- Standard IVF (stIVF)
In Vitro Maturation (IVM)
- IVM includes maturation of oocytes in controlled conditions in the laboratory as a part of the IVF treatment. IVM is indicated for patients at risk of ovarian hyperstimulation syndrome (OHSS) including polycystic ovary syndrome (PCOS) or PCO- like ovaries, and for patients who may be undergoing other treatments prior to which oocytes must be picked without maturation including cancer treatments.
- IVM requires low to no follicle stimulation and may provide health benefits to the female patient.
Frozen Embryo Transfer (FET)
FET involves freezing of the blastocysts from the IVF, and transfer after thawing. FET is indicated in cases of OHSS, other uterine abnormalities identified or complications during the processes, low endometrial receptivity/elevated progesterone or Preimplantation genetic screening. It may also be useful in cases of transfer of one fresh blastocyst, and freezing the others for future cycles.
Male Reproductive System
Female Reproductive System
Copulation to Conception
During orgasm, the male partner ejaculates the semen into the vagina of the female partner. At this stage, semen is thick and viscous, to protect sperms from the acidic environment of the vagina. The most motile sperms begin to travel through the cervical mucus into the uterus, leaving the seminal plasma behind. During ovulation, the barrier of the cervical mucus becomes thinner, and the pH of this environment becomes more favorable for the sperms. The sperms are transported up into the uterus towards the fallopian tubes due to contractile motion of the uterus.
As the sperms traverse through the uterus, they become biochemically capacitated due to the uterine chemical environment. As a result, the sperms show hyperactivity, and begin to undergo acrosome reaction, wherein the acrosome starts releasing its fluid components. The sperms are also attracted towards the oocyte due to chemical attraction known as chemotaxis.
Before the sperms reach the oocyte, they must first bind to the thin layer of cumulus cells outside the oocyte called corona radiata, and then to the glycoproteinaceous layer called zona pellucida (ZP). Upon binding to ZP, the acrosome reaction is triggered and the acrosome bursts, releasing the enzymes to facilitate penetration by the sperms. The enzymes also modify the ZP and harden it to prevent additional sperms to penetrate the ZP.
The sperms that reach the oocyte must bind to the JUNO protein in the oocyte membrane through the IZUMO1 protein in the sperm membrane. At this point, the oocyte immediately sheds away the JUNO from its membrane to prevent any more sperms from binding to it.
In the next step, sperm head and the oocyte fuse together and the sperm DNA is released into the oocyte. This is known as fertilization, and the zygote is formed.
The zygote matures into a multiple cell cluster called blastocyst over days, the ZP layer cracks open (zona hatching), and at around day 9 from ovulation, the embryo implants into the uterus.