Controlled ovarian hyperstimulation

Nomogram for the starting dosage of FSH preparation as estimated from age, antral follicle count (AFC) and endogenous serum FSH taken day 3 of the menstrual cycle. An example is given in the nomogram, wherein an age of 32 years and an AFC of 12 gives a point on the middle line that, when continued to an FSH of 5 IU/l, results in a starting FSH dosage of almost 200 IU/l.
Nomogram for the starting dosage of FSH as estimated from age, anti-Müllerian hormone (AMH) and endogenous serum FSH taken day 3 of the menstrual cycle (same as previous nomogram but with AMH instead of AFC).

Technique used in assisted reproduction involving the use of fertility medications to induce ovulation by multiple ovarian follicles.

- Controlled ovarian hyperstimulation

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Fertility medication

Fertility medications, also known as fertility drugs, are medications which enhance reproductive fertility.

Hypothalamic–pituitary–gonadal axis in females, with estrogen exerting mainly negative feedback on FSH secretion from the pituitary gland.

Controlled ovarian hyperstimulation, which is generally part of in vitro fertilization, and the aim is generally to develop multiple follicles (optimally between 11 and 14 antral follicles measuring 2–8 mm in diameter), followed by transvaginal oocyte retrieval, co-incubation, followed by embryo transfer of a maximum of two embryos at a time.

Artificial insemination

Deliberate introduction of sperm into a female's cervix or uterine cavity for the purpose of achieving a pregnancy through in vivo fertilization by means other than sexual intercourse or in vitro fertilisation.

Schematic illustration of human artificial insemination
The human female reproductive system. The cervix is part of the uterus. The cervical canal connects the interiors of the uterus and vagina.
Approximate pregnancy rate as a function of total sperm count (may be twice as large as total motile sperm count). Values are for intrauterine insemination. (Old data, rates are likely higher today)
A man performing artificial insemination of a cow.
A breeding mount with built-in artificial vagina used in semen collection from horses for use in artificial insemination
Artificial insemination tools brought from the USSR by Luis Thomasset in 1935 to work at Cambridge Laboratories and South America.

To improve the success rate of artificial insemination, drugs to create a stimulated cycle may be used, but the use of such drugs also results in an increased chance of a multiple birth.

Ovulation induction

Stimulation of ovulation by medication.

Hypothalamic–pituitary–gonadal axis in females, with estrogen exerting mainly negative feedback on follicle-stimulating hormone secretion from the pituitary gland.
Pregnancy rates in ovulation induction when using antiestrogens, as functions of the size of the leading follicle as measured by transvaginal ultrasonography at days 11 - 13 (bottom scale), as well as the thickness of the endometrial lining (4 different curves).

Controlled ovarian hyperstimulation (stimulating the development of multiple follicles of the ovaries in one single cycle), has also appeared in the scope of ovulation induction. Controlled ovarian hyperstimulation is generally part of in vitro fertilization, and the aim is generally to develop multiple follicles (optimally between 11 and 14 antral follicles measuring 2–8 mm in diameter), followed by transvaginal oocyte retrieval, co-incubation, followed by embryo transfer of a maximum of two embryos at a time.

Ovulation

Release of eggs from the ovaries.

Following a surge of luteinizing hormone (LH), an oocyte (immature egg cell) will be released into the uterine tube, where it will then be available to be fertilized by a male's sperm within 12 hours. Ovulation marks the end of the follicular phase of the ovarian cycle and the start of the luteal phase.
Ovulation occurs about midway through the menstrual cycle, after the follicular phase, and is followed by the luteal phase. Note that ovulation is characterized by a sharp spike in levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), resulting from the peak of estrogen levels during the follicular phase.
This diagram shows the hormonal changes around the time of ovulation, as well as the inter-cycle and inter-female variabilities in its timing.
Chance of fertilization by day relative to ovulation

Usually, ovarian stimulation is used in conjunction with ovulation induction to stimulate the formation of multiple oocytes.

Follicle-stimulating hormone

Gonadotropin, a glycoprotein polypeptide hormone.

FSH (α-FSH (green), β-FSH (orange)) with receptors (blue)
Reference ranges for the blood content of follicle-stimulating hormone levels during the menstrual cycle. 
 - The ranges denoted By biological stage may be used in closely monitored menstrual cycles in regard to other markers of its biological progression, with the time scale being compressed or stretched to how much faster or slower, respectively, the cycle progresses compared to an average cycle.
 - The ranges denoted Inter-cycle variability are more appropriate to use in non-monitored cycles with only the beginning of menstruation known, but where the woman accurately knows her average cycle lengths and time of ovulation, and that they are somewhat averagely regular, with the time scale being compressed or stretched to how much a woman's average cycle length is shorter or longer, respectively, than the average of the population.
 - The ranges denoted Inter-woman variability are more appropriate to use when the average cycle lengths and time of ovulation are unknown, but only the beginning of menstruation is given.
Follicle-stimulating hormone

FSH is used commonly in infertility therapy, mainly for ovarian hyperstimulation as part of IVF.

Transvaginal oocyte retrieval

Technique used in in vitro fertilization (IVF) in order to remove oocytes from the ovary of a woman, enabling fertilization outside the body.

Illustrated schematic of IVF with single-sperm injection (ICSI)

It is not unusual to remove 20 oocytes as women are generally hyperstimulated in advance of this procedure.

In vitro fertilisation

Process of fertilisation where an egg is combined with sperm in vitro ("in glass").

Illustrated schematic of IVF with single-sperm injection (ICSI)
A triple-line endometrium is associated with better IVF outcomes.
A depiction of the procedure of in-vitro fertilisation.
Demonstration of IVF
Normal Vaginal Canal Vs Menopause
Schematic illustration of artificial insemination.

The additional techniques that are routinely used in IVF include ovarian hyperstimulation to generate multiple eggs, ultrasound-guided transvaginal oocyte retrieval directly from the ovaries, co-incubation of eggs and sperm, as well as culture and selection of resultant embryos before embryo transfer into a uterus.

Gonadotropin-releasing hormone agonist

Type of medication which affects gonadotropins and sex hormones.

Leuprorelin, one of the most widely used GnRH agonists.
Buserelin
Deslorelin
Fertirelin
Gonadorelin (GnRH)
Goserelin
Histrelin
Nafarelin
Triptorelin

Suppression of spontaneous ovulation as part of controlled ovarian hyperstimulation, which is an essential component in in vitro fertilisation (IVF). Typically, after GnRH agonists have induced a state of hypoestrogenism, exogenous FSH is given to stimulate ovarian follicle, followed by human chorionic gonadotropins (hCG) to trigger oocyte release. GnRH agonists routinely used for this purpose are: buserelin, leuprorelin, nafarelin, and triptorelin.

Anti-Müllerian hormone

Glycoprotein hormone structurally related to inhibin and activin from the transforming growth factor beta superfamily, whose key roles are in growth differentiation and folliculogenesis.

AMH bound to its type II receptor, AMHR2 (PDB: 7L0J)

According to NICE guidelines of in vitro fertilization, an anti-Müllerian hormone level of less than or equal to 5.4 pmol/l (0.8 ng/mL) predicts a low response to ovarian hyperstimulation, while a level greater than or equal to 25.0 pmol/l (3.6 ng/mL) predicts a high response.

Folliculogenesis

Contrary to male spermatogenesis, which can last indefinitely, folliculogenesis ends when the remaining follicles in the ovaries are incapable of responding to the hormonal cues that previously recruited some follicles to mature.

Order of changes in ovary.<BR><BR>1 - Menstruation<BR>2 - Developing follicle<BR>3 - Mature follicle<BR>4 - Ovulation<BR>5 - Corpus luteum<BR>6 - Deterioration of corpus luteum
Diagram of folliculogenesis, starting from pre-antral (late secondary), courtesy NCBI
(a) The maturation of a follicle is shown in a clockwise direction proceeding from the primordial follicles. FSH stimulates the growth of a tertiary follicle, and LH stimulates the production of estrogen by granulosa and theca cells. Once the follicle is mature, it ruptures and releases the oocyte. Cells remaining in the follicle then develop into the corpus luteum. (b) In this electron micrograph of a secondary follicle, the oocyte, theca cells (thecae folliculi), and developing antrum are clearly visible. Electron microscopy images
"Percentage of ovarian reserve related to increasing age. The curve describes the percentage of ovarian reserve remaining at ages from birth to 55 years, based on the ADC model. 100% is taken to be the maximum ovarian reserve, occurring at 18–22 weeks post-conception. The percentages apply to all women whose ovarian reserve declines in line with our model (i.e. late and early menopause are associated with high and low peak NGF populations, respectively). We estimate that for 95% of women by the age of 30 years only 12% of their maximum pre-birth NGF population is present and by the age of 40 years only 3% remains. "
Section of the ovary. (#5 through #9 represent stages of folliculogenesis)
transitional primary follicle.

Performing controlled ovarian hyperstimulation leads to a greater recruitment of follicles, growing at about 1.6 mm per day.